PM2020 I+Endocrinology

01
A patient with type 2 diabetes mellitus is started on sitagliptin. What is

the mechanism of action of sitag liptin?
lncretin inhibitor
Dipeptidyl peptidase-4 (DPP-4) inhibitor
Alpha-glucosidase inhibitor
Glucagon inhibitor
Glucagon-like peptide-1 (GLP-1) mimetic
Submit answer
Reference ranges v
D1pept 1dyl pept idase-4 (DPP-4) 1nht61tor
Glucagon inhibitor
Gliptins = Dipeptidyl peptidase-4 (DPP-4) inhibitors

Importance: 50
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Diabetes mellitus: GLP-1 and the new drugs
A number of new drugs to treat diabetes mellitus have become

available in recent years. Much research has focused around the role of
glucagon-like peptide-1 (GLP-1), a hormone released by the small
intestine in response to an oral glucose load
Whilst it is well known that insulin resistance and insufficient 8-cell

compensation occur other effects are also seen in type 2 diabetes
mellitus (T2DM). In normal physiology an oral glucose load results in a
greater release of insulin than if the same load is given intravenously -
this known as the incretin effect. This effect is largely mediated by GLP-
1 and is known to be decreased in T2DM.
Increasing GLP-1 levels, either by the administration of an analogue

(glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting
its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins), is
therefore the target of two recent classes of drug.
Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide)
Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic.

These drugs increase insulin secretion and inhibit glucagon secretion.
One of the major advances of GLP-1 mlmetics is that they typically
result in weight loss, in contrast to many medications such as insulin,
sulfonylureas and thiazolid inediones. They are sometimes used in
combination with insulin in T2DM to minimise weight gain.
Exenatide must be given by subcutaneous injection within 60 minutes

before the morning and evening meals. It should not be given after a
meal.
Liraglutide is the other GLP-1 mimetic currently available. One the main
advantages of liraglutide over exenatide is that it only needs to be given
once a day.
Both exenatide and liraglutide may be combined w ith metformin and a

sulfonylurea. Standard release exenatide is also licensed to be used
with basal insulin alone or with metformin. Please see the BN F for a
more complete list of licensed indications.
NICE state the following:
Consider adding exenatide to metformin and a sulfonylurea if:

• BMI >= 35 kg/ m 2 in people of European descent and there are
problems associated with high weight, or
• BMI < 35 kg/ m 2 and insulin is unacceptable because of
occupational implications or weight Joss would benefit other
comorbidities.
I
NICE like patients to have achieved a 11 mmol/mol (1 %) reduction in

HbA1 c and 3% weight loss after 6 months to justify the ongoing
prescription of GLP-1 mimetics.
The major adverse effect of GLP-1 mimetics is nausea and vomiting.

The Medicines and Healthcare products Regulatory Agency has issued
specific warnings on the use of exenatide, reporting that is has been
linked to severe pancreatitis in some patients.
Dipeptidyl peptidase-4 {DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points
• oral preparation
• trials to date show that the drugs are relatively well tolerated with
no increased incidence of hypoglycaemia
• do not cause weight gain
NICE guidelines on DPP-4 inhibitors

• NICE suggest that a DPP-4 inhibitor might be preferable to a
thiazolidinedione if further weight gain would cause significant
problems, a thiazolidinedione is contraindicated or the person has
had a poor response to a thiazolidinedione
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Q2
A 33-year-old man with tingling in his t humb, index and middle finger
has been referred for endocrine consultation. He also complains of
waking up incredibly tired and says his wife comp lains that he snores.
On examination, he is noted to have a prominent brow ridge. Looking at
old photos, it becomes clear that his facia l appearance has drastically
changed over time. After some blood tests and an MRI scan, he is
prescribed octreotide. What is the mechanism of action of this drug?
Somatostatin analogue
Growth hormone receptor antagonist
Dopamine agonist
Dopamine antagonist
Insulin-growth factor 1 antagonist
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Reference ranges v
prescribed octreotide. What is the mechanism of action of this drug?
I Somatostatln analogue
Dopamine agonist
Dopamine antagonist
Insulin-growth factor 1 antagonist
Acromegaly is caused by excessive growth hormone.

Somatostatin directly inhibits the release of growth hormone, and
hence somatostatin analogues are used to treat acromegaly
Importance: 50
This question is two-fold. First, one has to recognise the symptoms of

acromegaly. Carpal tunnel syndrome and sleep apnoea are classic
complications of acromegaly. The changing nature of his face over time
is another clue. The second part of the question was to acknowledge
that octreotide, a useful treatment for acromegaly is a somatostatin
analogue.
Dopamine agonists were initially used to treat acromegaly but have

fallen out of favour due to superior treatments. Dopamine antagonists
have never been a treatment for acromegaly. An example of a growth
hormone antagonist is pegvlsomant. Growth hormone stimulates
insulin growth factor-1 release from the liver, but antagonists have not
been developed yet.
••
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f • Discuss (1) Improve
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Next question >
Acromegaly: management
Trans-sphenoidal surgery is the first-line treatment for acromegaly in

the majority of patients
Dopamine agonists
• for example bromocriptine
• the first effective medical treatment for acromegaly, however now
superseded by somatostatin analogues
• effective only in a minority of patients
• directly inhibits the release of growth hormone
• for example octreotide
• effective in 50-70% of patients
• may be used as an adjunct to surgery
Pegvisomant
• GH receptor antagonist - prevents dimerization of the GH receptor
• once daily s/c administration
• very effective - decreases IGF-1 levels in 90% of patients to normal
• doesn't reduce tumour volume therefore surgery still needed if
mass effect
External irradiation is sometimes used for older patients or following

failed surgical/medical treatment
Next question )
Q3
A 75-year-old woman presents with weight gain, lethargy and

constipation. She says that she has not changed her diet but has
started 'piling on the pounds'. She also feels 'bunged up' and is only
opening her bowels twice a week, and she used to go daily. She has
doubled her dose of senna but this hasn't made much difference. She
has a past medical history of hypothyroidism and has recently been
diagnosed with angina and iron deficiency anaemia. She takes
nifedipine, atorvastatin, aspirin, senna, levothyroxine and ferrous
sulphate.
Which of her medications is most likely to be the cause of this

presentation?
Nifedipine
Atorvastatin
Aspirin
Senna
Ferrous sulphate
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Atorvastatin
Aspirin
Senna
Ferrous sulphate
Iron / calcium carbonate tablets can reduce the absorption of

levothyroxine - should be given 4 hours apart
Importance: 50
Ferrous sulphate is correct. This woman is presenting with symptoms

of hypothyroidism - weight gain, lethargy and constipation. This is
despite treatment with levothyroxine, indicating that the hypothyroidism
is effectively undertreated.
Tablets containing iron can reduce the absorption of levothyroxine, and

as these have recently been started, this is the likely cause of the
symptoms. Tablets containing iron and levothyroxine should be taken at
least 2 and preferably over 4 hours apart to prevent this effect.
There is no interaction between levothyroxine and any of the other

medications.
116 it • Discuss Improve
CamScanne, -? Y.¥-> i.b . ~I

Hypothyroidism: management
Key points
• initial starting dose of levothyroxine should be lower in elderly
patients and those with ischaemic heart disease. The BNF
recommends that for patients with cardiac disease, severe
hypothyroidism or patients over 50 years the initial starting dose
should be 25mcg od with dose slowly titrated. Other patients
should be started on a dose of 50-1 00mcg od
• following a change in thyroxine dose thyroid function tests should
be checked after 8-12 weeks
• the therapeutic goal is 'normalisation' of the thyroid stimulating
hormone (TSH) level. As the majority of unaffected people have a
TSH value 0.5-2.5 mU/I it is now thought preferable to aim for a
TSH in this range
• women with established hypothyroidism who become pregnant
should have their dose increased 'by at least 25-50 micrograms
levothyroxine'* due to the increased demands of pregnancy. The
TSH should be monitored carefully, aiming for a low-normal value
• there is no evidence to support combination therapy with
levothyroxine and liothyronine
Side-effects of thyroxine therapy

• hyperthyroidism: due to over treatment
• reduced bone mineral density
• worsening of angina
• atrial fibrillation
Interactions
• iron, calcium carbonate
o absorption of levothyroxine reduced, give at least 4 hours
apart
Q4
A 46-year-old man with suspected diabetes mellitus has an oral glucose

tolerance test, following the standard WHO protocol. The following
resu lts are obtained:
Time (hours) Blood glucose (mmol/1)
0 5.7
2 7.6
How should these results be interpreted?
Normal
Impaired fasting glucose and impaired glucose tolerance
Diabetes mellltus
Impaired glucose tolerance
Impaired fasting glucose
Subm it answer
Reference ranges v
Normal
Diabetes mellitus
Both the fasting and two-hour glucose are within normal limits.
9' 1f • Discuss (1) Improve
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Diabetes mellitus (type 2): diagnosis
The diagnosis of type 2 diabetes mellitus can be made by either a

plasma glucose or a HbA1 c sample. Diagnostic criteria vary according
to whether the patient is symptomatic (polyuria, polydipsia etc) or not.
If the patient is symptomatic:

• fasting glucose greater than or equal to 7.0 mmol/1
• random glucose greater than or equal to 11.1 mmol/1 (or after 75g
oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be

demonstrated on two separate occasions.
CamSc.an,ner ~ '....,.i;lo-" ~ ~ I
Fasting glucose: a Ommoll >• 7,0 mmol,I
Horwalwu-iccontnll
M:IA It rs ~:'..'7 ITTnohnel II 0-e 4 l
Cl
~ I • "'G 'II 6 Hl 9 IM'IO'.I
Hb.A1c· <a 41 mmOllmo, - .. mmol.'mo,

1! ) I • )
I • values equal :o 1h11

celow • t0nsidcred norrno!
°' i e- l:!e 011Vnc:1$tC
U,tcshold far bet.es
·---
Diagram showing the spectrum of diabetes diagnosis
In 2011 WHO released supplementary guidance on the use of HbA1c on

the diagnosis of diabetes:
• a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is
diagnostic of diabetes mellitus
• a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude
diabetes (i.e. it is not as sensitive as fasting samples for detecting
diabetes)
• in patients without symptoms, the test must be repeated to
confirm the diagnosis
• it should be remembered that misleading HbA1 c results can be
caused by increased red cell turnover (see below)
Conditions where HbA1 c may not be used for diagnosis:

• haemoglobinopathies
• haemolytic anaemia
• untreated iron deficiency anaemia
• suspected gestational diabetes
• children
• HIV
• chronic kidney disease
• people taking medication that may cause hyperglycaemia (for
example corticosteroids)
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/I
implies impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose

less than 7.0 mmol/I and OGTT 2-hour value greater than or equal to 7.8
mmol/ 1but less than 11.1 mmol/1
Diabetes UK suggests:
• 'People with IFG should then be offered an ora l glucose tolerance
test to rule out a diagnosis of diabetes. A resu lt below 11 .1
mmol/I but above 7.8 mmol/1 indicates that the person doesn't
have diabetes but does have IGT.'
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QS
You are reviewing a 24-year-old man who has recently been diagnosed
with type 1 diabetes mellitus. He has no comorbidities and works as an
accountant. What HbA1 c target should he aim for initially?
42 mm ol/mol
45 mmol/mol
48 mmol/mol
50 mmol/ mol
52 mmol/mol
Submit answer
Reference ranges v
45 mmol/mol
48 mmol/ mol
50 mmol/mol
52 mmol/ mol
In type 1 diabetics, a general HbA 1c target of 48 mmol/mol (6.5%)

should be used
Importance: 50
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Diabetes mellitus: management of type 1
The long-term management of type 1 diabetics is an important and

complex process requiring the input of many different clin ical
specialties and members of the healthcare team. A diagnosis of type 1
diabetes can still reduce the life expectancy of patients by 13 years and
the micro and macrovascular complications are well documented.
NICE released guidelines on the diagnosis and management of type 1

diabetes in 2015. We've only highlighted a very select amount of the
guidance here which will be useful for any clinician looking after a
patient with type 1 diabetes.
HbA1c
• should be monitored every 3-6 months
• adults should have a target of HbA1c level of 48 mmol/mol (6.5%)
or lower. NICE do however recommend taking Into account factors
such as the person's daily activities, aspirations, likelihood of
complications, comorbidities, occupation and history of
hypoglycaemia
Self-monitoring of blood glucose

• recommend testing at least 4 times a day, including before each
meal and before bed
• more frequent monitoring is recommended if frequency of
hypoglycaemic episodes increases; during periods of illness;
before, during and after sport; when planning pregnancy, during
pregnancy and while breastfeeding
Blood glucose targets

• 5-7 mmol/I on waking and
• 4-7 mmol/I before meals at other times of the day
Type of insulin
• offer multiple daily injection basal-bolus insulin regimens, rather
than twice-daily mixed insulin regimens, as the insulin injection
regimen of choice for all adults
• twice-daily insulin detemir is the regime of choice. Once-daily
insulin glargine or insulin detemir is an alternative
• offer rapid-acting insulin analogues injected before meals, rather
than rapid-acting soluble human or animal insulins, for mealtime
insulin replacement for adults with type 1 diabetes
Metformin
• NICE recommend considering adding metformin if the BMI >= 25
kg/m 2
Q6
You are called to see a 34 year-old man in the late afternoon while you
are on-call. He suffers with type 1 diabetes mellitus and was admitted
after being diagnosed with diabetic ketoacidosis. He has been treated
with a fixed-rate insulin infusion with potassium replacement. He
usually takes Lantus glargine and Novorapid insulins, but the nurses
have not been administering these while he has been on his insulin
infusion. His latest arterial blood gas is shown:
pH 7.37
pC02 4.3 kPa
p02 11 .9kPa
Bicarbonate 26 mmol/L
Glucose 5.2 mmol/ L
What is the best course of action?
Stop insulin infusion now and restart normal insulin regimen
Give Novorapid insulin, then stop insulin Infusion with next meal
Continue insulin infusion overnight
Give 1Og oral glucose
Give Lantus glargine, then stop insulin infusion with next meal
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Reference ranges v
I Give Lantus glarglne, then stop Insulin Infusion with next meal
Stopping an insulin infusion in the context of an insulin-dependent

diabetic needs to be done with care. Long-acting insulins should be
continued throughout the duration of any insulin infusion, but in this
case this has not occurred - a not-uncommon problem on the wards.
The key focus here is that an Insulin-dependent diabetic should never

be without insulin as they risk precipitating diabetic ketoacidosis (DKA).
Option A will leave a gap in insulin therapy (the patient's next insulin
dose will be novorapid due with dinner) and risk recurrence of DKA.
Option B gives only a short acting insulin, which will have worn off by
the time the patient has his next meal. Option C is a safe choice, but
this patient no longer requires an insulin infusion as evidenced by his
normalised pH and blood glucose and continuing the infusion (with the
attendant hourly blood glucose checking) overnight is not in the
patient's best interests. Option D is inappropriate as the patient's blood
glucose is in the normal range. Option E is therefore the correct option -
it allows the patient's long-acting insulin to take effect before stopping
the insulin infusion. He should also restart his Novorapid insulin with
his next meal.
9' •t • Discuss (6) Improve
Next question )
Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) may be a complication existing type 1

diabetes mellitus or be the first presentation, accounting for around 6%
of cases. Rarely, under conditions of extreme stress, patients with type
2 diabetes mellitus may also develop DKA.
Whilst OKA remains a serious condition mortality rates have decreased

from 8% to under 1% in the past 20 years .
Pathophysiology
• DKA is caused by uncontrolled lipolysis (not proteolysis) which
results in an excess of free fatty acids that are ultimately
converted to ketone bodies
The most common precipitating factors of DKA are infection, missed

insulin doses and myocardial infarction.
Features
• abdominal pain
• polyuria, polydipsia, dehydration
• Kussmaul respiration (deep hyperventilation)
• Acetone-smelling breath ('pear drops' smell)
Diagnostic criteria
American Diabetes Joint British Diabetes Societies

Association (2009) (2013)
Key points Key points

• glucose > 13.8 • glucose > 11 mmol/1 or known
mmol/1 diabetes mellitus
• pH< 7.30 • pH< 7.3
• serum bicarbonate • bicarbonate < 1 5 m mol/1
<18 mmol/1 • ketones > 3 mmol/ 1or urine
• anion gap > 10 ketones ++ on dipstick
• ketonaemia
Management
• fluid replacement: most patients with OKA are deplete around 5-8
litres. Isotonic saline is used initially. Please see an example fluid
regime below.
• insulin: an intravenous infusion should be started at 0.1
unit/kg/hour. Once blood glucose is < 15 mmol/I an infusion of 5%
dextrose should be started
• correction of hypokalaemia
• long-acting insulin should be continued, short-acting insulin
should be stopped
JBDS example of fluid replacement regime for patient with a systolic

BP on admission 90mmHg and over
Fluid Volume
0.9% sodium chloride 1 L 1000ml over 1st hour
0.9% sodium chloride 1 L with potassium 1000ml over next 2

chloride hours

chloride hours

chloride hours

chloride hours

ch loride hours
Please note that slower infusion may be indicated in young adults (aged
18-25 years) as they are at greater risk of cerebral oedema.
JBDS potassium guidelines
Potassium level in first 24 Potassium replacement in mmol/L

hours (mmol/L} of infusion solution
Over 5.5 Nil
3.5-5.5 40
Below 3.5 Senior review as additional

potassium needs to be ,given
Complications of OKA and its treatment

• gastric stasis
• thromboembolism
• arrhythmi'as secondary to hyperkalaemia/iatrogenic hypokalaemia
• iatrogenic due to incorrect fluid therapy: cerebral oedema*,
hypokalaemia, hypoglycaemia
• acute respiratory distress syndrome
• acute kidney injury
* children/ young adults are particularly vulnerable to cerebral oedema

following fluid resuscitation in OKA and often need 1 :1 nursing to
monitor neuro-observations, headache, irritability, visual disturbance,
focal neurology etc. It usually occurs 4-12 hours following
commencement of treatment but can present at any time. If there is any
suspicion a CT head and senior review should be sought
Q7
Which one of the following is least characteristic of Addison's disease?
Hypoglycaemia
Metabolic alkalosis
Hyponatraemia
Hyperkalaemia
Positive short ACTH test
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Reference ranges v
Metabolic alkalosis
Hyponatraemia
Hyperkalaemia
Positive short ACTH test
Addison's disease is associated with a metabolic acidosis

Importance: 50
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Addison's disease: investigations
In a patient with suspected Addison's disease the definite investigation

is an ACTH stimulation test (short Synacthen test). Plasma cortisol ls
measured before and 30 minutes after giving Synacthen 250ug IM .
Adrenal autoantibodies such as anti-21-hydroxylase may also be
demonstrated.
If an ACTH stimulation test is not readily available (e.g. in primary care)

then sending a 9 am serum cortisol can be useful:
• > 500 nmol/I makes Addison's very unlikely
• < 100 nmol/1 is definitely abnormal
• 100-500 nmol/I shou ld prompt a ACTH stimulation test to be
performed
Associated electrolyte abnormalities are seen in around one-third of

undiagnosed patients:
• hyperkalaemla
• hyponatraemla
• hypoglycaemia
• metabolic acidosis
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Q8 fc:::J
Which of t he followi ng results est ablishes a diagnosis of diabetes

mellitus?
Asymptomatic patient with fast ing glucose 7. 9 mmol/L on one

occasion
Symptomatic patient with fasting glucose 6.8 mmol/L on two

occasions
Glycosuria +++
Asymptomatic patient with random glucose 22.0 mmol/ L on one

occasion
Symptomatic patient with random glucose 12.0 mmol/L on one

occasion
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Reference ranges v
Symptomatic patient with fasting glucose 6.8 mmol/L on two
occasions
Glycosuria +++
Asymptomatic patient with random glucose 22.0 mmol/L on one

occasion
Symptomatic patient with random glucose 12.0 mmol/ L on one

occasion
Diabetes diagnosis: fasting > 7.0, random > 11.1 - if

asymptomatic need two readings
Importance: 50
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Q9 Jc::l
A 43-year-old woman is referred to the endocrine clinic w ith symptoms

of weight gain, fatigue and headache. She was also recently diagnosed
with type two diabetes.
On examination, you note truncal obesity with proximal wasting of the

arms and legs. Hirsutism is present, and the skin appears thin with
multiple striae and bruises.
You suspect Cushing's syndrome and perform routine blood tests as

part of your investigations.
What biochemical abnormality would you expect to ftnd in this

condition?
Hypercalcaemia
Hyperkalaemic metabolic acidosis
Hyperkalaemic metabolic alkalosis
Hypokalaemic metabolic acidosis
Hypokalaemic metabolic alkalosis
Submit answer
Reference ranges v
I Hypokalaemic metabolic alkalosis
Cushing's syndrome - hypokalaemic metabolic alkalosis

Importance: 50
This patient has presented with several characteristic features of

Cushing's syndrome.
In terms of biochemical abnormalities seen on routine testing,

Cushing's syndrome often results in impaired glucose tolerance and
hyperglycaemia, as seen in this patient. A hypokalaemic metabolic
alkalosis can also be seen, as a result of increased renal
mineralocorticoid action from the excess cortisol. This results in an
increased exchange of sodium and water for potassium and H+, leading
to a hypokalaemic metabolic acidosis.
This picture is also seen in Conn's syndrome.
Hypercalcaemia is not usually associated with Cushing's syndrome.
116 1f • Discuss (1) Improve
Next question )
Cushing's syndrome: investigations
Investigations are divided into confirming Cushing's syndrome and then

localising the lesion. A hypokalaemic metabolic alkalosis may be seen,
along with impaired glucose tolerance. Ectopic ACTH secretion (e.g.
secondary to small cell lung cancer) is characteristically associated
with very low potassium levels. An insulin stress test is used to
differentiate between true Cushing's and pseudo-Cushing's
Tests to confirm Cushing's syndrome

The two most commonly used tests are:
• overnight dexamethasone suppression test (most sensitive)
• 24 hr urinary free cortisol
Localisation tests
The first-line localisation is 9am and midnight plasma ACTH (and

cortisol) levels. If ACTH is suppressed then a non-ACTH dependent
cause is likely such as an adrenal adenoma
Both low- and high-dose dexamethasone suppression tests may be

used to localise the pathology resulting in Cushing's syndrome. These
tests may be interpreted as follows:
Cortisol result Interpretation
Not suppressed by low-dose Cushing's syndrome not due to

dexamethasone primary causes, i.e. likely secondary
to corticosteroid therapy
Not suppressed by low- Cushing's disease

dose, but suppressed by
high-dose dexamethasone
Not suppressed by low- or Ectopic ACTH syndrome likely

CRH stimulation
• if pituitary source then cortisol rises
• if ectopic/ adrenal then no change in cortisol
Petrosal sinus sampling of ACTH may be needed to differentiate

between pituitary and ectopic ACTH secretion
0 Q10
A 41-year-old man presents with recurrent headaches. These typica lly

occur 2-3 times a day and are associated with sweating and
palpitations. As he was concerned that it may be due to blood pressure
he borrowed his fathers home monitor. During these episodes his blood
pressure is around 210/11 O mmHg. Given the likely diagnosis, what is
the most appropriate next test?
MRI adrenals
Phenoxybenzamine suppression test
24 hour urinary collection of vanillylmandelic acid
24 hour urinary collection of metanephrines
24 hour urinary collection of catecholamines
Submit answer
Reference ranges v
Phenoxybenzamine suppression test
24 hour urinary collection of vanillylmandelic acid
24 hour urinary collection of metanephrines
24 hour urinary collection of catecholamines
Phaeochromocytoma: do 24 hr urinary metanephrines, not

catecholam ines
Importance: 50
Three 24 hour collections are needed as some patients have

intermittently raised levels.
" If t9 Discuss (3) Improve ]

Phaeochromocytoma
Phaeochromocytoma is a rare catecholamine secreting tumour. About

10% are familial and may be associated with MEN type II,
neurofibromatosis and van Hippel-Lindau syndrome
Basics
• bilateral in 10%
• malignant in 10%
• extra-adrenal in 10% (most common site = organ of Zuckerkandl,
adjacent to the bifurcation of the aorta)
Features are typically episodic

• hypertension (around 90% of cases, may be sustained)
• headaches
• palpitations
• sweating
• anxiety
Tests
• 24 hr urinary collection of metanephrines (sensitivity 97%*)
• this has replaced a 24 hr urinary collection of catecholamines
(sensitivity 86%)
Surgery is the definitive management. The patient must first however be

stabilized with medical management:
• alpha-blocker (e.g. phenoxybenzamine), given before a
• beta-blocker (e.g. propranolol)
*BMJ 2012; 344 doi: http://dx.doi.org/ 10.1136/ bmj.e1042 (Published

20 February 2012)
Next uestion )
Q11
A 25-year-old man with a family history of multiple endocrine neoplasia

type 1 is reviewed in clinic. What is the single most useful investigation
to monitor such patients?
Short synacthen test
Urinary catecholamines
Serum calcium
Thyroid function tests
Serum prolactin
Submit answer
Reference ranges v
Urinary catecholamines
Serum calcium
Serum prolactin
Peptic ulceration, galactorrhoea, hypercalcaemia - multiple

endocrine neoplasia type I
Importance: 50
The high incidence of parathyroid tumours and hypercalcaemia make

serum calcium a useful indicator of MEN type 1 in suspected
individuals
9' at - Discuss Improve
Next question )
Multiple endocrine neoplasia
The table below summarises the three main types of multiple endocrine
neoplasia (MEN). MEN is inherited as an autosomal dominant disorder.
MEN type I MEN type Ila MEN type llb
Medullary thyroid Medull ary thyroid

3 P's
cancer {70%) cancer
Parathyroid (95%):
hyperpa rathyro id ism 2 P's 1p
due to parathyroid
hyperplasia Parathyroid (60%) Phaeochromocytom,
Pituitary (70%) Phaeochromocytoma
Pancreas (50%): e.g. Marfanoid body
insulinoma, habitus
gastrinoma (leading Neuromas
to recurrent peptic
ulceration)
Also: adrenal and

thyroid
MEN1 gene RET oncogene RET oncogene
Most common
presentation =
hypercalcaemia
MEN type 1
Pancreatic tumours
(e.g. gastrinoma,
insulinoma)
Pituitary tumours
(e .g. prolactinoma)
Primary
hyperparathyroidism
MEN type 2a MEN type 2b
Phaeochromocytoma
Marfanoid body habitus
Medullary thyroid
cancer
Neuromas
RET oncogene
C Passmed'C.ne com
Q12
You review a 47-year-old man one year after he was diagnosed with
prediabetes. Last year he had a HbA 1 c taken after being diagnosed as
having hypertension. This was recorded as being 43 mmol/ mol (6.1%).
His most recent blood test is recorded as being 45 mmol/mol (6.3%)
despite the patient reporting that he has changed his diet as instructed
and exercising three times a week. His body mass index (BMI) today is
26.5 kg/m 2 • Last year it was 27.5kg/m 2 . What is the most appropriate
course of action?
Start metformin
Start pioglitazone
Review again in 12 months
Start orlitstat
Do a oral glucose tolerance test
Submit answer
Reference ranges v
Start metformin
Start pioglitazone
Review again in 12 months
Start orlitstat
Do a oral glucose tolerance test
NICE recommend metformin for adults at high risk 'whose blood

glucose measure (fasting plasma glucose or HbA 1c) shows they are still
progressing towards type 2 diabetes, despite their participation in an
intensive lifestyle-change programme'.
116 11
Next question )
Prediabetes and impaired glucose regulation
Prediabetes is a term which is increasingly used where there is

impaired glucose levels which are above the normal range but not high
enough for a diagnosis of diabetes mellitus. The term includes patients
who have been labelled as having either impaired fasting glucose (IFG)
or impaired glucose tolerance (IGT). Diabetes UK estimate that around
1 in 7 adults in the UK have prediabetes. Many individuals with
prediabetes will progress on to developing type 2 diabetes mellitus
(T2DM) and they are therefore at greater risk of microvascular and
macrovascular complications.
Terminology
• Diabetes UK currently recommend using the term prediabetes
when talking to patients and impaired glucose regulation when
talkina to other healthcare orofessionals
• research has shown that the term 'prediabetes' has the most
impact and is most easily understood
Identification of patients with prediabetes

• NICE recommend using a validated computer based risk
assessment tool for all adults aged 40 and over, people of South
Asian and Chinese descent aged 25-39, and adults with
conditions that increase the risk of type 2 diabetes
• patients identified at high risk should have a blood sample taken
• a fasting plasma glucose of 6.1-6.9 mmol/1 or an HbA 1 c level of
42-47 mmol/mol (6.0-6 .4 %) indicates high risk
Fasting glucose: <s C.O mmol !I >• 7,0mmol l
~,c is ~l-AT n-rnol'mel Oo..e ~ l
" ~~
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gV.OM 6 1~ l> l'M'<CL1
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1e
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="lcw e comiocred nomwil
Management
• lifestyle modification: weight loss, increased exercise, change in
diet
• at least yearly follow-up with blood tests is recommended
• NICE recommend metformin for adults at high risk 'whose blood
glucose measure (fasting plasma glucose or HbA 1c) shows they
are still progressing towards type 2 diabetes, despite their
participation in an intensive lifestyle-change programme'
There are two main types of IGR:

• impaired fasting glucose (IFG) - due to hepatic insulin resistance
• impaired glucose tolerance (IGT) - due to muscle insulin
resistance
• patients with IGT are more likely to develop T2DM and
cardiovascular disease than patients with IFG
Definitions
• a fasting glucose greater than or equal to 6.1 but less than 7.0
mmol/ 1implies impaired fasting glucose (IFG)
• impaired glucose tolerance (IGT) is defined as fasting plasma
glucose less than 7.0 mmol/1 and OGTT 2-hour value greater than
or equal to 7.8 mmol/ 1but less than 11 .1 mmol/ 1
• people with IFG should then be offered an oral glucose tolerance
test to rule out a diagnosis of diabetes. A result below 11 .1
mmol/ 1but above 7.8 mmol/1 indicates that the person doesn't
have diabetes but does have IGT
Next question )
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Search
Q13
An 18-year-old male is reviewed due to concerns about delayed pubertal

development, despite being 1.77m tall. On examination he has scant
pubic hair and reduced testicular volume. The following blood results
are obtained:
Testosterone 6.7 nmol/I {9 - 30)
LH 3 .1 mu/I (3-10)
FSH 5.7 mu/I (3 -10)
What is the most likely diagnosis?
Klinefelter's syndrome
Acute lymphoblastic leukaemia
Testicular feminisation syndrome
Primary testicular failure
Kallman's syndrome
Submit answer
Reference ranges v
Acute lymphoblastic leukaemia
Testicular feminisation syndrome
Primary testicular failure
Kallman's syndrome
Klinefelter's - LH & FSH raised

Kallman's - LH & FSH low-normal
Importance: 50
The LH and FSH levels are inappropriately low-normal given the low
testosterone concentration, which points towards a diagnosis of
hypogonadotrophic hypogonadism. In Klinefelter's syndrome the LH
and FSH levels are raised
8' if • Discuss (6) Improve
Next question )
I
Next question )
Kallmann's syndrome
Kallmann's syndrome is a recognised cause of delayed puberty

secondary to hypogonadotrophic hypogonadism. It is usually inherited
as an X-linked recessive trait. Kallmann's syndrome is thought to be
caused by failure of GnRH-secreting neurons to migrate to the
hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy

with delayed puberty
Features
• 'delayed puberty'
• hypogonadism, cryptorchidism
• anosmia
• sex hormone levels are low
• LH, FSH levels are inappropriately low/normal
• patients are typically of normal or above average height
Cleft lip/palate and visual/hearing defects are also seen in some

patients
Next question)
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Save my notes
0 Q14
A 64-year-old man with a history of type 2 diabetes comes to the clin ic

for review. His HbA1c is elevated at 64 mmol/ mol despite taking 1g of
metformin 8D. On examination his blood pressure is 142/88 mmHg, his
pulse is 82 beats per minute and regular. His body mass index is
elevated at 33 kg/m 2 • A decision is made to start him on dapagliflozin.
Which of the fo llowing would you expect on starting therapy?
Hypoglycaemia
Increased blood pressure
Increased serum urate
Increased total cholesterol
Weight gain
Submit answer
Reference ranges v
Increased blood pressure
Increased serum urate
Increased total cholesterol
Weight gain
SGLT-2 inhibitors like dapagliflozin promote increased glucose excretion

because they inhibit glucose reabsorption in the kidney. This
corresponds to a calorie load of 200-400 kcal per day. In some patients,
this results in dramatic weight loss, although on average this equates to
1-2% reduction in weight over 6 months. SGLT-2 inhibitors are
recognised to increased total cholesterol, (both HDL and LDL), although
cardiovascular outcome studies as yet do not suggest this translates
into increased risk of MACE events. In fact, the EM PA-reg study with
empagliflozin demonstrated a reduction in overall mortality.
Hypoglycaemia is not a feature of SGLT2 inhibitor use and SGLT-2

inhibitors are associated with increased urate excretion rather than an
increase in serum uric acid.
https://www.evidence.nhs.uk/ formulary/ bnf/current/6-endocrine-

system/61-drugs-used-in-diabetes/612-antidiabetic-drugs/6123-other-
antidiabetic-drugs/ dapagliflozin
http://www.nejm.org/ doi/ full/ 10.1056/ NEJMoa1504720#t=article
,6 •• t9 Discuss (3) Improve ]
Next question )
9' •• • Discuss (3) Improve
Next question >
SGLT-2 inhibitors
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2

(SGLT-2) in the renal proximal convolut ed tubule to reduce glucose
reabsorption and increase urinary glucose excretion.
Examples include canagliflozin, dapagliflozin and empagliflozin.
Important adverse effects include

• urinary and genital infection (secondary to glycosuria). Fournier's
gangrene has also been reported
• normoglycaemic ketoacidosis
• increased risk of lower-limb amputat ion: feet shou ld be closely
monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial
in type 2 diabetes mellitus.
Next question >
B I A ... ·-
·- 1-
~
- - ...
Save my notes
Q15
A 18-year-old man with a background of Marfan syndrome presents to

the emergency department with palpitations and sweating. He was
hypertensive on admission at 198/ 101 mmHg. He Is also complaining
of the development of nodules on his torso and cheek which provide a
pins and needle like sensation. A 24 hour urinary catecholamine has
been sent and is currently pending.
What is the most likely underlying diagnosis?
Thyroid carcinoma
MEN type 2A
MEN type 1
MEN type 2B
Pheochromocytoma
Submit answer
Reference ranges v
MEN type 2A
MEN type 1
MEN type 2B
Pheochromocytoma
Medullary thyroid cancer, phaeochromocytoma, marfanoid body

habitus - multiple endocrine neoplasia type lib
Importance: 50
When differentiating between MEN 2A and 28, it is worth remembering

that MEN 28 has similar characteristics as MEN 2A (Thyroid
carcinoma's, Adrenal tumours, Parathyroid hyperplasia) but in addition
typically have a Marfanoid appearance and mucosa! neuromas, as well
as the absence of hyperparathyroidism.
MEN type 1 is characterised by pancreatic neuroendocrine tumours,

pituitary adenoma and parathyroid hyperplasia.
8' •• tt Discuss (5) Improve
Next question )
Q16
A 48-year-old lady is seen in the diabetes clinic with uncontrolled blood

sugars ranging from 14 mmol/L to 22 mmol/L. She has a past medical
history of type 2 diabetes, ischaemic heart disease, rheumatoid arthritis
and recurrent episodes of thrush alongside chronic obstructive
pulmonary disease. Her body mass index is 30. Which medical co-
morbidity is the strongest contraindication to starting an SGLT2
(sodium glucose transport protein 2) inhibitor class of drugs?
lschaemic heart disease
Chronic obstructive pulmonary disease
Type 2 diabetes
Rheumatoid arthritis
Recurrent thrush
Submit answer
Reference ranges v
Chronic obstructive pulmonary disease
Type 2 diabetes
Recurrent thrush
Dapagliflozin is a newer drug for the treatment of diabetes. It is a

member of the sodium-glucose transport protein 2 (SGLT2) inhibitor
class of drugs.
SGLT2 inhibitors prevent the resorption of glucose from the proximal

renal tubule, resulting in more glucose being secreted in the urine. Due
to an increased amount of glucose being secreted in the urine, these
medications are contra-indicated in patients with recurrent thrush. The
increased amount of glucose in the urine is thought to predispose to
bacterial growth. It should also be noted that urine dip sticks will test
positive for glucose.
The other medications in this class include: canagliflozin &

empagliflozin
The other answers are distractors with no known contraindication to

SGLT2 inhibitor use in ischaemic heart disease, chronic obstructive
pulmonary disease or rheumatoid arthritis. SGLT2's are indicated in
patients with type 2 diabetes. Note that although trials are ongoing,
SGLT2 inhibitors are not currently licensed as an adjunct in patients
with type 1 diabetes.
Q17
A 51-year-old woman who is known to have poorly controlled type 1

diabetes mellitus is reviewed. Her main presenting complaint is bloating
and vom iting after eating. She also notes that her blood glucose
readings have become more erratic recently. Which one of the following
medications is most likely to be beneficial?
He/icobacter pylori eradication therapy
Lansoprazole
Amitriptyline
Metoclopramide
Cyclizine
Submit answer
Reference ranges v
Lansoprazole
Amitriptyline
Metoclopramide
Cyclizine
The true prevalence of gastroparesis in patients with type 1 diabetes

mellitus is not known but most modern studies estimate around 5% are
affected. This leads to both upper gastrointestinal symptoms and
erratic glucose control due to gastric emptying dysfunction.
Metoclopramide is a pro-kinetic drug that can improve gastric emptying.
" •• _, Discuss (1) Improve ]
Next question )
Diabetic neuropathy
Diabetes typically leads to sensory loss and not motor loss in peripheral
neuropathy. Painful diabetic neuropathy is a common problem in
clinical practice.
NICE updated it's guidance on the management of neuropathic pain in

2013. Diabetic neuropathy is now managed in the same way as other
forms of neuropathic pain:
• first-line treatment: amitriptyline, duloxetine, gabapentin or
pregabalin
• if the first-line drug treatment does not work try one of the other 3
drugs
• tramadol may be used as 'rescue therapy' for exacerbations of
neuropathic pain
• topical capsaicin may be used for localised neuropathic pain (e.g.
post-herpetic neuralgia)
• pain management clinics may be useful in patients with resistant
problems
Gastrointestinal autonomic neuropathy
Gastroparesis
• symptoms include erratic blood glucose control, bloating and
vomiting
• management options include metoclopramide, domperidone or
erythromycin (prokinetic agents)
Chronic diarrhoea
• often occurs at night
Gastro-oesophageal reflux disease

• caused by decreased lower esophageal sphincter (LES) pressure
Q18 {CJ
A 53-year-old male presents to the Emergency Department complaining

of extreme fatigue. He has a background of treated Graves disease. On
examination his blood pressure is 103/ 58 mmHg, pulse 64/ min and
temperature 36.3°C. The following results are obtained:
Na+ 135 mmol/ 1
K+ 5.4 mmol/1
Urea 5.2 mmol/ 1
Creatinine 42 umol/1
TSH 3.5 mu/ I
Free thyroxine (T4) 12 pmol/ 1
You arrange for a random cortisol test however whilst awaiting the
result he becomes unresponsive. In addition to giving intravenous
steroid and fluid, what test is it imperative to check first given the likely
diagnosis?
Serum calcium
ECG
Arterial pH
Prolactin
Glucose
Submit answer
I
CamScanner -! W~ :.i.;,-~\
I Glucose l
's disease. The
This que stio n is alluding to a diag nos is of Addison
low bloo d pressure
auto imm une history, raised potassium, fatig ue and
are all clues to this .
ing hypoglycaemia
Patients with Addison 's disease are prone to develop
ids. Given the
due to loss of the gluc oge nic effe ct of gluc oco rtico
checked.
sudden deterioration in GCS, a glucose level mus t be
Addison 's disease:

Addison's is adre noc ortic al insu ffici enc y due to the
cts both
dys func tion /des truc tion of the adrenal cortex. It affe
eral oco rtico id (sal t
gluc oco rtico id (me tabo lism of gluc ose etc.) and rnin
eloped wor ld is
balance) function. The com mon est cause in the dev
tion of the cort ex
auto imm une adrenalitis. Other causes include des truc
by infe ctio ns such as TB, or met asta sis.
Signs/ sym ptom s of Addisonian cris is:
Neurological
• syncope
• con fusi on
• lethargy
• convulsions
Haemodynamic
• hypotension
• hypothermia
Biochemical
• hyponatraemia
• hyperkalaernia
• hypoglycaemia
Cu,,1Scilnr1cf _, L,J;.4 .i.> _........i..t.l'

Management of Addisonian crisis (medical emergency):
• intravenous fluids
• corticosteroids (e.g iv dexamethasone)
Note: iv dexamethasone is often preferred as this will not interfere with

cortisol assays needed for a short synacthen test, unlike
hydrocortisone.
a6 1f - Discuss (5) Improve ]
'
Next question )
Addisonian crisis
Causes
• sepsis or surgery causing an acute exacerbation of chronic
insufficiency (Addison's, Hypopituitarism)
• adrenal haemorrhage eg Waterhouse-Friderichsen syndrome
(fulminant meningococcemia)
• steroid withdrawal
Management
• hydrocortisone 100 mg im or iv
• 1 litre normal saline infused over 30-60 mins or with dextrose if
hypoglycaemic
• continue hydrocortisone 6 hourly until the patient is stable. No
fludrocortisone is required because high cortisol exerts weak
mineralocorticoid action
• oral replacement may begin after 24 hours and be reduced to
maintenance over 3-4 days
Next question )
C Q19 Jr::J
A 23-year-old woman presents for review. She has not had a normal
period for around 8 months now. A recent pregnancy test was negative.
Blood tests are ordered:
FSH 2.2 IU/ L (0-20 IU/ L)
Oestradiol 84 pmol/I (100-500 pmol/ 1)
Thyroid stimulating hormone 3.1 mlU/ L
Prolactin 2 ng/ ml (0-1 0 ng/ ml)
Free androgen index 3(< 7)
What is the most likely cause of her symptoms?
Prolactinoma
Premature ovarian failure
Polycystic ovarian syndrome
Addison's disease
Excessive exercise
Submit answer
Reference ranges v
CamScanne, -? Y.¥-> i.b. ~I

Addison's disease
Excessive exercise
The bloods show a hypothalamic amenorrhoea which may be caused

by stress or excessive exercise. The FSH would be raised in premature
ovarian failure.
[ ,6 'f • Discuss (5) Improve ]
Next question )
Amenorrhoea
Amenorrhoea may be divided into prima ry (failure to start mense s by
the age of 16 years) or secondary (cessation of established, regular
menstruation for 6 month s or longer).
Causes of primary amenorrhoea

• Turner's syndrome
• testicu lar feminisation
• congenital adrenal hyperplasia
• congenital malfo rmatio ns of the genital tract
Secondary amenorrhoea is defined as when menst ruatio n has

previously occurred but has now stopp ed for at least 6 month s.
Causes of secondary amenorrhoea (after excluding pregnancy)

• hypothalamic amenorrhoea (e.g. Stress, excessive exercise)
• polycystic ovarian syndrome (PCOS)
• hyperprolactinaemia
• premature ovarian failure
• thyrot oxicos is*
• Sheehan's syndrome
• Asherman's syndrome (intrauterine adhesions)
Initial investigations
• exclude pregnancy with urinary or serum bHCG
• gonadotrophins: low levels indica te a hypot halam ic cause where
as raised levels sugge st an ovarian problem (e.g. Premature
ovarian failure)
• prolactin
• androgen levels: raised levels may be seen in PCOS
• oestradiol
• thyroid functio n tests
*hypothyroidism may also cause amenorrhoea

Q20
A 56-year-old man is reviewed in the Cardiology outpatient clinic

following a myocardial infarction one year previously. During his
admission he was found to be hypertensive and diabetic. He complains
that he has put on 5kg in weight in the past 6 months. Which of his
medications may be contributing to his weight gain?
Metformin
Losartan
Clopidogrel
Gliclazide
Simvastatin
Submit answer
Reference ranges v
Losartan
Clopidogrel
Gliclazide
Simvastatin
Sulfonylureas often cause weight gain

Importance: 50
[ .. •• ,- Discuss (3) Improve ]
Next question )
Next question )
Sulfonylureas
Sulfonylureas are oral hypoglycaemic drugs used in the management of

type 2 diabetes mellitus. They work by increasing pancreatic insulin
secretion and hence are only effective if functional 8-cells are present.
On a molecular level they bind to an ATP-dependent K+(KArP) channel
on the cell membrane of pancreatic beta cells .
Common adverse effects

• hypoglycaemic episodes (more common with long-acting
preparations such as chlorpropamide)
• weight gain
Rarer adverse effects

• hyponatraemia secondary to syndrome of inappropriate ADH
secretion
• bone marrow suppression
• hepatotoxicity (typically cholestatic)
• peripheral neuropathy
Sulfonylureas shou ld be avoided in breastfeeding and pregnancy.
Next question >
B I l!!J A ...,
Q21
Which one of the following skin disorders is least associated with

hypothyroidism?
Xanthomata
Pruritus
Pretibial myxoedema
Eczema
Dry, coarse hair
Submit answer
Reference ranges v
I _ a_ ~ ~ - ~
Pretibial myxo_e_d_em
Eczema
Dry, coarse hair
is
For the purposes of postg radu ate exam s pretibial myxo edem a
of it
associated with thyrotoxicosis. There are however case repo rts
pittin g
been foun d in hypothyroid patients, especially the diffu se non-
variety
[ ,6 ,. • Discu ss (1) Im prove ]
Next ques tion )
Skin disorders associated with thyroid dis eas e
Skin man ifesta tions of hypo thyro idism

• dry (anhydrosis), cold, yellowish skin
• non-pitting oedema (e.g. hands, face)
• dry, coarse scalp hair, loss of lateral aspe ct of eyebrows
• eczema
• xanth oma ta
Skin man ifesta tions of hype rthyr oidis m

e
• pretibial myxoedema: erythematous, oede mato us lesions abov
the lateral malleoli
• thyroid acropachy: clubbing
• scalp hair thinning
• increased swea ting
Pruritus can occu r in both hyper- and hypo thyro idism

Q22
A 57-year-old man with a known history of type-2 diabetes presents to

clinic for a review. He currently takes metformln only for his diabetes
and reports following the regime as instructed.
His HbA 1c is 63 mmol/mol (target = 53mmol/mol) and the clinician and

patient decide he should start a sulfonylurea in addition to his
metformin.
Which of the following best describes the new treatment's mechanism

of action?
Increases stimulation of insulin secretion by pancreatic 8-cells

and decreases hepatic clearance of insulin
Inhibits sodium-glucose co-transporter-2 in the proximal

convoluted tubule of the nephron to stop glucose reabsorption,
meaning it is excreted in urine
Inhibits the principal enzyme that breaks down GLP-1 - an incretin

hormone that increases insulin secretion and suppresses
glucagon secretion
Reduces hepatic gluconeogenesis, increases peripheral glucose

uptake and also reduces the absorption of carbohydrate in the
gut
Upregulation of transcription of insulin responsive genes, leading

to an increase in glucose transporters and insulin receptors at
the surface of the cell
Submit answer
Increases stimulation of insulin secretion by pancreatic 8-cells and
decreases hepatic clearance of insulin
Inhibits sodium-glucose co-transporter-2 in the proximal convoluted

tubule of the nephron to stop glucose reabsorption, meaning it is
excreted in urine

hormone that increases insulin secretion and suppresses glucagon
secretion

uptake and also reduces the absorption of carbohydrate in the gut
Upregulation of transcription of insulin responsive genes, leading to

an increase in glucose transporters and insulin receptors at the
surface of the cell
Sulfonyureas increase stimulation of insulin secretion by

pancreatic 8-cells and decrease hepatic clearance of insulin
Importance: 50
The correct answer is option 1 as sulfonylureas are insulin

secretagogues - one of the classes of oral hypoglycaemic agents. [,]
Option 2 best describes the mechanism of action of SGLT-2 inhibitors

(dapagliflozin, canagliflozin).l2l
Option 3 best describes the mechanism of action of DPP-4 inhibitors

(sitagliptin, vildagliptin).l3l
Option 4 best describes the mechanism of action of metformin, an

insulin sensitiser.l4l
Option 5 best describes the mechanism of action of thiazolidinediones

(pioglitazone), also an insulin sensitiser,[41
di ,u I t:µu1 L~ 1u11owing 1ne regime as instructed.
His HbA 1 c is 63 mmol/mol (target = 53mmol/mol) and the clinician and

patient decide he should start a sulfonylurea in addition to his
metformin.
Which of the following best describes the new treatment's mechanism

of action?
Increases stimulation of insulin secretion by pancreatic B-cells and

decreases hepatic clearance of insulin
Inhibits sodium-glucose co-transporter-2 in the proximal convoluted

tubule of the nephron to stop glucose reabsorption, meaning it is
excreted in urine

hormone that increases insulin secretion and suppresses glucagon
secretion

uptake and also reduces the absorption of carbohydrate in the gut
Upregulation of transcription of insulin responsive genes, leading to

an increase in glucose transporters and insulin receptors at the
surface of the cell
Sulfonyureas increase stimulation of insulin secretion by

pancreatic 8-cells and decrease hepatic c learance of insulin
Importance: 50
Ca mSc.an,ner ~ '....,.i;lo-" ~ ~ I
Importance: 50
The corre ct answ er is optio n 1 as sulfonylureas are insulin

1
secre tago gues - one of the class es of oral hypo glyca emic agents. [ 1
Option 2 best desc ribes the mech anism of actio n of SGLT-2 inhibitors
2
(dap aglifl ozin, cana gliflo zin).[ 1
Optio n 3 best desc ribes the mech anism of actio n of DPP-4 inhibitors
3
( sitag liptin , vilda glipti n). [ ]
Optio n 4 best desc ribes the mech anism of actio n of metf ormi n, an
insul in sens itiser.[4]
es
Option 5 best desc ribes the mech anism of actio n of thiazolidinedion
4
(piog litazo ne), also an insul in sensitiser,[ 1
Acco rding to NICE, metf ormi n should be the first drug treat ment of
choic e for thos e peop le who can tolera te it. The second medication, to
be given in comb inatio n with metf ormi n, can be any one of the four
types of oral hypo glyca emic agents listed_[sJ
Q23
A 44-year-old woman presents with a neck lump. She reports tiredness

and fatigue and has put on around 3kilograms of weight recently; she
reports going up 3 belt notches. Her blood results show normocytic
anaemia.
On palpation of her neck, a hard, fixed, painless lump is felt.
Which one of the following complications is associated with her

condition?
Hyperthyroidism
Retroperitoneal fibrosis
Ascites
Atrial fibrillation
Photosensitivity
Submit answer
Reference ranges v
Retroperitoneal fibrosis
Ascites
Atrial fibrillation
Photosensitivity
Riedel's thyroiditis is associated with retroperitoneal fibrosis

Importance: 50
Riedel thyroiditis (RT) is characterized by the replacement of normal

thyroid parenchyma with dense fibrotic tissue and by the extension of
this fibrosis to adjacent structures of the neck. Most patients are
euthyroid, but hypothyroidism is noted in approximately 30% of cases.
Patient's may present with a painless neck lump and symptoms of

hypothyroidism such as weight gain, tiredness, fatigue and intolerance.
Riedel's thyroiditis is not associated with hyperthyroidism, ascites or

photosensitivity and therefore these answers are incorrect.
Atrial fibrillation is a complication of hyperthyroidism and patients with

AF should have their thyroid function assessed. However, there is no
evidence to suggest that Riedel's thyroiditis is associated with atrial
fibrillation .
[ ,6 'f tit Discuss (2) Improve
Next question )
Next question )
Riedel's thyroiditis
Riedel's thyroiditis is a rare cause of hypothyroidism characterised by

dense fibrous tissue replacing the normal thyroid parenchyma. On
examination a hard, fixed, painless goitre is noted. It is usually seen in
middle-aged women. It is associated with retroperitoneal fibrosis.
Hypothyroidism Hyperthyrodlsm
H sh tmo10'$
thyroid tlS Subaculti thyrokf
(d Ou rv n' )
Ri
--
rs lhyroid1t11
Postpartum thYTOkfius
Am:.odarone
Gr ves' dis a
Toxic mu t nodular g01tre
~ .......
Venn diagram showing how different causes of thyroid

dysfunction may manifest. Note how many causes of
hypothyroidism may have an initial thyrotoxic phase.
Next question )
B J I!!! A • ·- 2:
1- - - ....
Q24
A 93-year-old female who lives alone comes to see you regarding

troublesome urge incontinence. Over the past year, you have noted a
steady decline and she is becoming increasingly frail. She has had a
number of falls while rushing to the bathroom, resulting in attendance
at the local emergency department. She previously underwent a course
of bladder retraining with no significant improvement in symptoms.
What would be the most appropriate treatment of her urge

incontinence?
Pelvic floor exercises
Immediate release oxybutynin
Mirabegron
Doxazosin
Surgical repair
Submit answer
Reference ranges v
Mirabegron
Doxazosin
Surgical repair
Oxybutynin should not be used in frail older women with urinary

incontinence due to the risk of impairment of daily functioning,
confusion and acute delirium
Importance: 50
The correct answer here is mirabegron. According to the latest NICE

guidance, first line medical treatment of urge incontinence after bladder
retraining can be with oxybutynin, tolterodine or darifenacin. NICE has
1
issued a do not use' statement on the use of oxybutynin in frail elderly
women due to the risk of cognitive impairment, falls and general
decline. This is particularly the case with immediate release
preparations. There is no similar statement for tolterodine or
darifenacin. A trial or tolterodine or darifenacin, may have been an
appropriate answer if this option was given, although these are also
associated with anticholinergic side effects. Given the patients• history
of general decline and recurrent falls, avoidance of an anticholinergic
and treatment with mirabegron would, therefore, be a more appropriate
choice than oxybutynin.
Oxybutynin is normally the antimuscarinic of choice in urge

incontinence, however, has a high anticholinergic burden. Per NICE
guidance it should be avoided in frail older women due to an increased
risk of delirium, confusion and impaired function. Given the patients'
age, history of gradual decline and recurrent falls, oxybutynin should be
avoided. This is particularly the case, given that she lives alone and so
increased confusion or delirium may not be picked up straight away,
increasing her risk of falls.
Pelvic floor exercises are used in conservative management of stress

incontinence not urge incontinence.
and urinary
Doxazosin is used in the trea tme nt of hypertension
inco ntin enc e.
retention. It is likely to worsen her sym pto ms of urge
ntinence.
Surgery is indicated in stress as opposed to urge inco
[ ,. •• tt Discuss Improve ]
Next que stio n )
Urinary incontinence
ctin g around 4-5 %

Urinary incontinence (UI) is a com mon problem , affe
ales .
of the population. It is mor e com mon in elderly fem
Risk fact ors

• advancing age
• previous pregnancy and chil dbir th
• high body mas s index
• hysterectomy
• fam ily history
Classification
to detr uso r
• overactive bladder (OAB)/urge incontinence: due
overactivity
coughing or
• stress incontinence: leaking sma ll amo unts when
laughing
• mixed incontinence: both urge and stress
tion, e.g. due
• overflow incontinence: due to bladder out let obstruc
to prostate enlargement
Initial investigation
• bladder diaries should be compl eted for a minim um of 3 days
• vaginal examination to exclude pelvic organ prolapse and ability to
initiate voluntary contra ction of pelvic floor muscl es ('Kegel'
exercises)
• urine dipstic k and culture
• urodynamic studies
Management depends on wheth er urge or stress UI is the predo minan t

picture. If urge incontinence is predominant:
• bladder retraining (lasts for a minim um of 6 weeks, the idea is to
gradually increase the intervals between voiding)
• bladder stabilising drugs: antim uscar inics are first-line. NICE
recommend oxybutynin (imme diate release), toltero dine
(imme diate release) or darifenacin (once daily preparation).
Immediate release oxybutynin should, however, be avoided in 'frail
older women'
• mirabegron (a beta-3 agoni st) may be useful if there is concern
about anticholinergic side-e ffects in frail elderly patien ts
If stress incontinence is predominant:

• pelvic floor muscle training: NICE recom mend at least 8
contra ctions performed 3 times per day for a minim um of 3
month s
• surgical procedures: e.g. retropubic mid-urethral tape procedures
Next questi on >

r---------------------------
B I ~ A ...
Save my notes
Q25
th centre with
An 18-year-old man presents to the nurse at the local heal
has vague
a third episode of balanitis over the past 3 mon ths. He also
diag nose d with
sym ptom s of tiredness. His fathe r and gran dfath er were
He is slim with a
type 1 diabetes and take a basal-bolus insulin regimen.
ia on urine
body mas s index of 22 kg/m . He is note d to have glycosur
2
dips tick testi ng.
A fasti ng bloo d sample show s the follo wing :
Na+ 140 mmol/ 1
K+ 3.9 mmo l/ 1
Urea 6.1 mmol/ 1
Creatinine 91 µmol/ 1
Glucose 9.2 mmol/ 1
Which of the follo wing is the mos t likely diagnosis?
Latent auto imm une diabetes of adul ts (LADA)
Matu rity onse t diabetes of the young (MODY)
Renal glycosuria
Type 1 diabetes
Type 2 diabetes
Sub mit answer
Reference ranges v
CamScanne r ➔ •..;~ L - ~1
Maturity onset diabetes of the young (MODY)
Renal glycosuria
Type 1 diabetes
Type 2 diabetes
MODY is autosomal dominant diabetes mellitus which often presents

for the first time in young slim individuals without symptoms of polyuria
and polydipsia. Insidious onset with for instance with recurrent balanitis
as here is usual. It's important to recognise the diagnosis because
many patients with MODY including those with the HNF-7 alpha form of
the disease can be managed with sulphonylureas for many years before
needing to start insulin therapy. Evaluation of family history and testing
for antibodies for type 1 diabetes can help to differentiate MODY from
other forms of diabetes mellitus.
Type 1 diabetes isn't associated with such strong heritability as that

seen here, and given this patient's body habitus, type 2 diabetes is very
unlikely. LADA is associated with a body habitus similar to the
overweight / obese picture seen in type 2 diabetes for many patients,
although progression to insulin therapy occurs more quickly. Renal
glycosuria is ruled out by the elevated fasting glucose seen here.
[ " " - Discuss (6) Improve ]
Next question )
MODY
Maturity-onset diabetes of the young (MODY) is characterised by the

development of type 2 diabetes mellitus in patients< 25 years old. It is
typically inherited as an autosomal dominant cond ition. Over six
different genetic mutations have so far been identified as leading to
MODY.
It is thought that around 1-2% of patients with diabetes mellitus have

MODY, and around 90% are misclassified as having either type 1 or type
2 diabetes mellitus.
MODY3
• 60% of cases
• due to a defect in the HNF-1 alpha gene
• is associated with an increased risk of HCC
MODY2
• 20% of cases
• due to a defect in the glucokinase gene
MODY 5
• rare
• due to a defect in the HNF-1 beta gene
• liver and renal cysts
Features of MODY
• typically develops in patients < 25 years
• a family history of early onset diabetes is often present
• ketosis is not a feature at presentation
• patients with the most common form are very sensitive to
sulfonylureas, insulin is not usually necessary
Q26
A 61-year-old woman is investigated for hoarseness and dyspnoea

which has got progressively worse over the past month. ln the past she
has been diagnosed with toxic multinodular goitre which was
successfully treated with radioiodine. On examination she has a firm,
asymmetrical swelling of the thyroid gland. Laryngoscopy
demonstrates a right vocal cord paralysis and apparent external
compression of the trachea . What is the most likely diagnosis?
Follicular thyroid cancer
Papillary thyroid cancer
Medullary thyroid cancer
Lymphoma of the thyroid gland
Anaplastic thyroid cancer
Submit answer
Reference ranges v
( Anaplastic t hyroid cancer
---------
Anaplastic thyroid cancer - aggressive, difficult to treat and often

causes pressure symptoms
Importance: 50
9' if tt Discuss (3) Improve
Next question )
Thyroid cancer
Features of hyperthyroidism or hypothyroidism are not commonly seen

in patients with thyroid malignancies as they rarely secrete thyroid
hormones
Main points
Type Percentage
Papillary 70% Often young females - excellent

prognosis
Follicular 20%
Medullary 5% Cancer of parafollicular (C) cells,

secrete calcitonin, part of MEN-2
Anaplastic 1% Not responsive to treatment, can

cause pressure symptoms
Lymphoma Rare Associated w ith Hashimoto's

Papillary thyroid cancer
Medullary thyroid cancer
Lymphoma of the thyroid gland
IAnaplastic thyroid cancer
Anaplastic thyroid cancer - aggressive, difficult to treat and often

causes pressure symptoms
Importance: 50
[ ,. .. • Discuss (3) Improve ]
CamScanne, -? Y.¥-> i.b.~I

Thyroid cancer

hormones
Main points
Type Percentage

prognosis
Follicular 20%


Lymphoma Rare Associated with Hashimoto's

thyroiditis
Management of papillary and follicular cancer

• total thyroidectomy
• followed by radioiodine (1-131) to kill residual cells
• yearly thyroglobulin levels to detect early recurrent disease
Papillary • Usually contain a mixture of papillary and
carcinoma colloidal filled follicles
• Histologically tumour has papillary projections
and pale empty nuclei
• Seldom encapsulated
• Lymph node metastasis predominate
• Haematogenous metastasis rare
Follicular • Usually present as a solitary thyroid nodule

adenoma • Malignancy can only be excluded on formal
histological assessment
Follicular • May appear macroscopically encapsulated,

carcinoma microscopically capsular invasion is seen.
Without this finding the lesion is a follicular
adenoma.
• Vascular invasion predominates
• Multifocal disease raree
Medullary • C cells derived from neural crest and not thyroid

carcinoma tissue
• Serum calcitonin levels often raised
• Familial genetic disease accounts for up to 20%
cases
• Both lymphatic and haematogenous metastasis
are recognised, nodal disease is associated with
a very poor prognosis.
Anaplastic • Most common in elderly females

carcinoma • Local invasion is a common feature
• Treatment is by resection where possible,
palliation may be achieved through
isthmusectomy and radiotherapy.
Chemotherapy is ineffective.
Q27 JC::,
The fasting glucose for a patient is reported as follows:
Glucose (fasting) 6.3 mmol/1
What is the most likely underlying pathophysiological change?
Beta-cell hyperplasia
Beta-cell atrophy
Muscle insulin resistance
Hepatic insulin resistance
Adipose tissue insulin resistance
Submit answer
Reference ranges v
I Hepatic insulin resistance
Adipose tissue insulin resistance
"' •t • Discuss (1) Improve
Next question )

Terminology
talking to other healthcare professionals

• a fasting plasma glucose of 6.1-6. 9 mmol/1 or an HbA 1 c level of
42-47 mmol/mol (6.0-6.4%) indicates high risk
Fasting glucose: ea Omrno11 >-7,0mmol.'I
~.!.It 11 ,:...;?rm,ol mcl 16 o:.fl .1"-l

or
" no O'-'«>M ~ ,~ ~ mmo:,
HbA1c· oi 41 mmollmot >• 4' rnmol'mo4

15 ) I )
1 c Inc ~noitc
tnrc:shol:1 IOf b::'es
Management
diet

resistance
Definitions
mmol/1 implies impaired fasting glucose (IFG)
glucose less than 7.0 mmol/ 1and OGTT 2-hour value greater than
or equal to 7.8 mmol/1 but less than 11.1 mmol/ 1
test to rule out a diagnosis of diabetes. A result below 11.1
mmol/1 but above 7.8 mmol/ 1indicates that the person doesn't
Next question )
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Save my notes
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O. Google search on "Prediabetes and impaired glucose regulation"
Links
Q28
An obese 48-year-old man presents with lethargy and polydipsia. What

is the minimum HbA1c that wou ld be diagnostic of type 2 diabetes
mellitus?
Cannot use HbA1 c for diagnosis
6.0% (42 mmol/mol)
6.3% (45 mmol/mol)
6.5% (48 mmol/mol)
7.0% (53 mmol/mol)
Submit answer
Reference ranges v
Q29
A 42-year-old man presents to his GP feeling generally unwell. For the

past three months he has been experiencing daily frontal headaches
which have not been helped by regular paracetamol. He has also
noticed some unusual symptoms such as his wedding ring no longer
fitting, his shoe size apparently increasing and a small amount of milky
discharge from both nipples. On examination his blood pressure is
168/96 mmHg. What is the most likely diagnosis?
Phaeochromocytoma
Cushing's syndrome
Diabetes insipidus
Macroprolactinoma
Acromegaly
Submit answer
Reference ranges v
I Acrom egaly
[ ,t •• • Discu ss (1) Impro ve ]
Next quest ion )
Acromegaly: features
In acrom egaly there is exces s growt h hormo ne secon dary to a pituita ry

adeno ma in over 95% of cases . A minor ity of cases are cause d by
ectop ic GHRH or GH produ ction by tumou rs e.g. pancr eatic.
Features
• coarse facial appearance, spade-like hands, increa se in shoe size
• large tongue, progn athism , interd ental space s
• excessive sweat ing and oily skin: cause d by sweat gland
hyper trophy
• featur es of pituita ry tumou r: hypop ituitar ism, headaches,
bitemp oral hemia nopia
• raised prolac tin in 1 / 3 of cases -+ galact orrhoe a
• 6% of patien ts have MEN-1
Comp licatio ns
• hyper tensio n
• diabet es (>10%)
• cardio myopa thy
• colore ctal cance r
Next quest ion )

Q30
A 32-year-old male presents with a 10-day history of a worsening rash

on his back and chin . He does not complain of pain or pruritus but is
concerned as the rash is unsightly. His past medical history includes
ulcerative colitis which is being treated with prednisolone due to a
recent flare-up 7 weeks ago and is responding well. He does not smoke,
use tobacco nor alcohol and works as a gardener.
On examination, he has uniform papules with some small pustules with

moderate erythema over his upper trunk, back and jaw. There are no
comedones nor cysts. Vital signs are normal.
Which of the following is the most likely cause of this patient's skin
rash?
Acne vulgaris
Drug-induced adverse effect
Erythema nodosum
Occupational exposure to herbicides
Suppurative folliculitis ( Pseudomonas aeruginosa )
'
Submit answer
Drug-induced adverse effect
Erythema nodosum
Occupational exposure to herbicides
Suppurative folliculitis ( Pseudomonas aeruginosa )
Systemic glucocorticoids can cause drug-induced acne. This is

characterised as monomorphic papular rash without comedones
or cysts. This does not respond to acne treatment but improves
on drug discontinuation
Importance: 50
This patient has drug-induced acne is most commonly caused by

glucocorticoids and androgens but can also be precipitated by
1
azathioprine, phenytoin, antipsychotics, and isoniazid
This typically present s as monomorphic papules and pustules with no

comedones, cysts or nodules within 2 weeks of starting medication.
This subset of patients will not respond to standard acne treatment,
discontinuation of offending agents typical ly clears up the rash.
Acne vulgaris displays lesions in various stages of development and

typically occurs in the face in adolescence.
Dermal manifestations of 180 include erythema nodosum, pyoderma

and pyoderma gangrenosum. Erythema nodosum presents as tender
red nodules, typically on legs and arms.
Herbicides, fungicides, and insecticides contain halogenated aromatic

hydrocarbons. Halogenated compounds can cause occupational acne
(also known as chloracne). Th is rash is characterised by inflammatory
nodules and large comedones.
suppurative folliculitis is most often caused by Staphylococcus aureus,
it can also be caused by pseudomonas.
References
(1) 4. Du-Thanh A, Kluger N, Bensalleh H, Guillot B. Drug-Induced
Acneiform Eruption. American Journal of Clinical Dermatology.
2011 ;12(4):233-245.
a, Rf tt Discuss (1) Improve
Next question >
Corticosteroids: side-effects
Glucocorticoid side-effects
• endocrine: impaired glucose regulation, increased appetite/ weight
gain, hirsutism, hyperlipidaemia
• Cushing's syndrome: moon face, buffalo hump, striae
• musculoskeletal: osteoporosis, proximal myopathy, avascular
necrosis of the femoral head
• immunosuppression: increased susceptibility to severe infection,
reactivation of tuberculosis
• psychiatric: insomnia, mania, depression, psychosis
• gastrointestinal: peptic ulceration, acute pancreatitis
• ophthalmic: glaucoma, cataracts
• dermatological: acne
• suppression of growth in children
• intracranial hypertension
• neutrophilia
Mineralocorticoid side-effects
• fluid retention
• hypertension
Q31
A 54-year-old man w ith type 2 diabetes mellitus is reviewed in clinic. He

is currently taking pioglitazone, metformin, aspirin and simvastatin.
Which one of the following problems is most likely to be caused by
pioglitazone?
Photosensitivity
Thrombocytopaenia
Myalgia
Peripheral oedema
Hyponatraemia
Submit answer
Reference ranges v
I Peripheral oedema
Hyponatraemia
Pioglitazone may cause fluid retention

Important for me Less important
[ ,6 1f tit Discuss (3) Improve ]
Next question >
Thiazolidinediones
Thiazolidinediones are a class of agents used in the treatme nt of type 2

diabetes mellitus . They are agonists to the PPAR-gamma receptor and
reduce peripheral insulin resistance. Rosiglitazone was withdraw n in
201 O following concerns about the ca rdiovasc ular side-effe ct profile.
The PPAR-gamma receptor is an intracellular nuclear receptor. It's

natural ligands are free fatty acids and it is thought to control adipocy te
different iation and function.
Adverse effects
• weight gain
• liver impairment: monitor LFTs
• fluid retention - therefore contrain dicated in heart failure. The risk
of fluid retention is increased if the patient also takes insulin
• recent studies have indicated an increased risk of fracture s
• bladder cancer: recent studies have shown an increased risk of
bladder cancer in patients taking pioglitaz one (hazard ratio 2.64)
Next question >

0 Q32
A 55-year-old taxi driver with type 2 diabetes mellitus comes for review.
When he was diagnosed 12 months ago he was started on metformin
and the dose was titrated up. His IFCC-HbA 1 cone year ago was 75
mmol/mol (DCCT-HbA 1 c 9%) and is now 69 mmol/mol (8.5%). His body
mass index is 33 kg/m 2 . What is the most appropriate next step in
management?
Add exenatide
Add sitagliptin
Add glipizide
Make no changes t o his medication
Add insulin
Submit answer
Reference ranges v
Add sitagliptin
Add glipizide
Make no changes to his medication
Add insulin
His HbA1c is still significantly above target so some change to the

medication is indicated.
The NICE type 2 diabetes mellitus guidelines would generally advocate

the use of a sulfonylurea in this situation.
However. the patient is a taxi driver and overweight. A DPP-4 inhibitor

such as sitagliptin would be ideal in this situation. There is no risk of
hypoglycaemia and they DPP-4 inhibitors are weight neutral.
Next question )
NICE updated its guidance on the management of type 2 diabetes

mellitus (T2DM) in 2015. Key points are listed below:
• HbA 1c targets have changed. They are now dependent on what
antidiabetic drugs a patient is receiving and other factors such as
frailty
• there is more flexibility in the second stage of treating patients
(i.e. after metformin has been started) - you now have a choice of
4 oral antidiabetic aoents
It's worthwhile thinking of the average patient who is taking
metformin for T2DM, you can titrate up metformin and encourage
lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but
should only add a second drug if the HbA 1c rises to 58 mmol/mol
(7.5%)
Dietary advice
• encourage high fibre, low glycaemic index sources of
carbohydrates
• include low-fat dairy products and oily fish
• control the intake of foods containing saturated fats and trans
fatty acids
• limited substitution of sucrose-containing foods for other
carbohydrates is allowable, but care should be taken to avoid
excess energy intake
• discourage use of foods marketed specifically at people with
diabetes
• initial target weight loss in an overweight person is 5-10%
HbA1c targets
This is area which has changed in 2015

• individual targets should be agreed with patients to encourage
motivation
• HbA 1c should be checked every 3-6 months until stable, then 6
monthly
• NICE encourage us to consider relaxing targets on 'a case-by-case
basis, with particular consideration for people who are older or frail,
for adults with type 2 diabetes'
• in 2015 the guidelines changed so HbA1c targets are now
dependent on treatment:
Lifestyle or single drug treatment
HbA1c
Management of T2DM target
Lifestyle 48
mmol/mol
(6.5%)
Lifestyle+ metformin 48
mmol/mol
(6.5%)
Includes any drug which may cause hypoglycaemia 53

(e.g. lifestyle+ sulfonylurea) mmol/mol
(7.0%)
Practical examples
• a patient is newly diagnosed with HbA 1c and wants to try lifestyle
treatment first. You agree a target of 48 mmol/mol (6.5%)
• you review a patient 6 months after starting metformin. His
HbA 1c is 51 mmol/mol (6.8%). You increase his metformin from
500mg bd to 500mg tds and reinforce lifestyle factors
Patient already on treatment
Management of T2DM HbA1 c target
Already on one drug, but HbA1c has risen to 58 53 mmol/mol

mmol/mol (7.5%) (7.0%)
Metformin Metformin not tolerated or Cl
Mettorrmn Glitpln
OR
Sulfonylurea
OR
HbA1c > 58 mmol/mol (7.5%) PloglltaZone
Metformfn
i 1- gltpun
HbA1c > 58 mmolimol (7 5%)
OR I
Metrormln .., su1rony1urea
OR
Metformin • pioglrtazone Ghplln + p1oghtazone
OR OR
Metformln + SGLT-2 Inhibitor Gllptm + sulfonylurea
OR
Plogotazone + sulfonylUrea
HbA1c > 58 mmoL1mol (7 5~o)
Metformin 1- gllptm 1- sul1on\ lurea

OR
r.tetformm + p1091nazone + sulfonylurea HbA1c > 58 mmoVmol (7.5%}
OR
Metformin + sulfon~ lurea + SGLT -2 anh1b1tor
OR
Metform1n + p109lttazone + SGLT-2 inh1b1tor
lnsuun
Triple therapy ·nor effecwe, nor ro'eraced or conua•'ld caced·
AND
Br.tl > 35
i
Metform1n + sulfonylurea -+- GLP-1 muneuc 0 Passmed,cme corn
Drug treatment
The 2015 NICE guidelines introduced some changes into the

management of type 2 diabetes. There are essentially two pathways,
one for patients who can tolerate metformin, and one for those who
can't
Metroonln nO( tolerated or Cl

,-..uormln
Tolerates metformin:
• metformin is still first-line and should be offered if the HbA 1c
rises to 48 mmol/mol (6.5%)* on lifestyle interventions
• if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug
should be added from the following list:
• - sulfonylurea
• - gliptin
• - pioglitazone
• - SGLT-2 inhibitor
• if despite this the HbA1c rises to, or remains above 58 mmol/mol
(7.5%) then triple therapy with one of the following combinations
should be offered:
• - metformin + gliptin + sulfonylurea
• - metformin + pioglitazone + sulfonylurea
• - metformin + sulfonylurea + SGLT-2 inhibitor
• if despite this the HbA 1c rises to, or remains above 58 mmol/mol
should be offered:
• -. metformin + gliptin + sulfonylurea
• -. metf ormin + pioglitazone + sulfonylurea
• -. metformin + sulfonylurea + SGLT-2 inhibitor
• -. metformin + pioglitazone + SGLT-2 inhibitor
• -. OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic ( e.g. exenatide)

• if triple therapy is not effective, not tolerated or contraindicated
then NICE advise that we consider combination therapy with
metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1)
mimetic if:
• _. BMI >= 35 kg/ m 2 and specific psychological or other medical
problems associated with obesity or
• _. BMI < 35 kg/ m 2 and for whom insulin therapy would have
significant occupational implications or
weight loss would benefit other significant obesityrelated comorbidities

• only continue if there is a reduction of at least 11 rnmol/mol
[1.0%] in HbA1c and a weight loss of at least 3% of initial body
weight in 6 months
Practical examples
• you review an established type 2 diabetic on maximum dose
metformin. Her HbA1 c is 55 mmol/mol (7.2%). You do not add
another drug as she has not reached the threshold of 58
mmol/ mol (7.5%)
• a type 2 diabetic is found to have a HbA 1c of 62 mmol/ mol (7.8%)
at annual review. They are currently on maximum dose metformin.
You elect to add a sulfonylurea
Cannot tolerate metformin or contraindicated
• if the HbA1c rises to 48 mmol/ mol (6.5%)* on lifestyle
interventions, consid er one of the followi ng:
• -- sulfonylurea
• -- gliptin
• _. pioglitazone
• if the HbA1c has risen to 58 mmol/ mol (7.5%) then a one of the
followi ng combin ations should be used:
• -- gliptin + pioglitazone
• -- gliptin + sulfonylurea
• -- pioglitazone + sulfonylurea
• if despite this the HbA 1c rises to, or remains above 58 mmol/ mol
(7.5%) then consid er insulin therapy
Starting insulin
• metfor min should be continued. In terms of other drugs NICE
advice: 'Review the continu ed need for other blood glucos e lowerin g
therapies '
• NICE recommend starting with human NPH insulin (isopha ne,
intermediate acting) taken at bed-tim e or twice daily accord ing to
need
Risk factor modification
Blood pressure
• target is< 140/ 80 mmHg (or < 130/ 80 mmHg if end-organ
damage is present)
• ACE inhibitors are first-line
Anti platelets
• should not be offered unless a patient has existing cardiov ascula r
disease
CamScanner ~ '..J~ ~ j,,-,&a:'I

Lipids
• following the 2014 NICE lipid modification guidelines only patients
with a 10-year cardiovascular risk > 10% (using QRISK2) should be
offered a statin. The first-line statin of choice is atorvastatin 20mg
on
Primary pqvenUon Secondary prevention
10.yur catdiov'aKia risk • 10,. OR IIOWnlldlNmtc!w-,dilffMOR

fflClll t)1le 1 --..CS OR
CKD I eOFII IOdB•ilhl)
...,_.,.,....._
~ia,dleaNOR
Atorvaslatin 20mg od
Ator,rastatin IOmg od
d ron-HDL l'..at noc ,_,, by .,,. ~
CCNidlf n-.ig '4> IOIOmg
Graphic showing choice of statin.
*this is a bit confusing because isn't the diagnostic criteria for T2DM
HbA1c 48 mmol/mol (6.5%)? So shouldn't all patients be offered
metformin at diagnosis? Our interpretation of this is that some patients
upon diagnosis will elect to try lifestyle measures, which may reduce
their HbA1c below this level. If it then rises to the diagnostic threshold
again metformin should be offered
Next question >
Save my notes
Q33
A 34-year-old female presents with fever and lower abdominal pain.

Over the past five days she has noticed deep dyspareunia and some
post-coital bleeding. Her last period began 1 O days ago. She is diffusely
tender in the suprapubic area and vaginal examination reveals cervical
excitation. Endocervical swabs are taken. A diagnosis of pelvic
inflammatory disease Is suspected. What is the most appropriate
management?
Oral doxycycline
Await endocervical swab results
Oral amoxicillin + ciprofloxacin
Oral doxycycline + ciprofloxacin
Oral ofloxacin + metronidazole
Submit answer
Reference ranges v
I Oral ofloxac in + metronidazole
Treatment of pelvic inflammatory disease: oral ofloxacin + oral

metronidazole or intramuscular ceftriaxone + oral doxycycline +
oral metronidazole
Importance: 50
Consensus guidelines recommend treatment once a diagnosis of pelvic

inflammatory disease is suspected, rather than waiting for the results of
swabs
at 22 ,, 30
at f
1 tt Discuss (2) Improve
Next question >
Pelvic inflammatory disease
Pelvic inflammatory disease (PID) is a term used to describe infection

and inflammation of the female pelvic organs including the uterus,
fallopian tubes, ovaries and the surrounding peritoneum. It is usually the
result of ascending infection from the endocervix.
Causative organisms
• Chlamydia trachomatis
+ the most common cause

• Neisseria gonorrhoeae
• Mycoplasma genitalium
• Mycop/asma hominis
Peaiures
• lower abdominal pain
• fever
• deep dyspareunia
• dysuria and menstru al irregularities may occur
• vaginal or cervical discharg e
• cervical excitation
Investigation
• a pregnancy test should be done to exclude an ectopic pregnan cy
• high vaginal swab
o these are often negative
• screen for Chlamyd ia and Gonorrhoea
Manage ment
• due to the difficulty in making an accurate diagnosis, and the
potential complica tions of untreate d PIO, consens us guidelin es
recomm end having a low threshol d for treatme nt
• oral ofloxacin + oral metronid azole or intramus cular ceftriaxo ne +
oral doxycycline + oral metronid azole
• RCOG guidelines suggest that in m ild cases of PIO intrauter ine
contraceptive devices may be left in. The more recent BASHH
guidelines suggest that the evidence is limited but that 'Remova l
of the IUD should be considered and may be associat ed with better
short term clinical outcome s'
Complic ations
• perihepatitis (Fitz-Hugh Curtis Syndrome)
0 occurs in around 10% of cases
0 it is characte rised by right upper quadran t pain and may be
confuse d with cholecys titis

• infertility - the risk may be as high as 10-20% after a single
episode
• chronic pelvic pain
• ectopic pregnancy
Q34
A 25-year-old male develops type 2 diabetes mellitus. Which one of the

following genes is most likely to be responsible?
Glucokinase
HNF-1 alpha
HNF-4 alpha
HNF-1 beta
IPF-1
Submit answer
Reference ranges v
Q34 ,c
A 25-year-old male develops type 2 diabetes mellitus. Which one of the

following genes is most likely to be responsible?
Glucokinase
HNF-1 alpha
HNF-4 alpha
HNF-1 beta
IPF-1
116 11
Next question )
MODY
rised by the
Matu rity-o nset diabetes of the youn g (MODY) is char acte
years old. It is
deve lopm ent of type 2 diab etes mell itus in patie nts < 25
. Over six
typic ally inhe rited as an auto som al dom inan t cond ition
as lead ing to
diffe rent gene tic muta tions have so far been iden tified
MODY.
mell itus have

It is thou ght that around 1-2% of patie nts with diab etes
r type 1 or type
MODY, and around 90% are misc lass ified as having eithe
2 diab etes mell itus.
MOD Y3
• 60% of case s
• due to a defe ct in the HNF-1 alpha gene
• is asso ciate d with an increased risk of HCC
MODY2
• 20% of case s
• due to a defe ct in the gluc okin ase gene
MODY 5
• rare
• due to a defe ct in the HNF-1 beta gene
• liver and rena l cyst s
Features of MODY
• typic ally develops in patie nts < 25 years
• a fami ly histo ry of early onse t diab etes is ofte n pres ent
• keto sis is not a featu re at pres enta tion
to
• patie nts with the mos t com mon form are very sens itive
sulfo nylu reas, insu lin is not usua lly nece ssar y
Nex t ques tion )

CamSca nne r ➔ •..;~ L - ~1
Q35
A 33-year-old female is referred to endocrinology with thyrotoxicosis.

Following a discussion of management options she elects to have
radioiodine therapy. Which one of the following is the most likely
adverse effect?
Hypothyroidism
Thyroid malignancy
Agranulocytosis
Oesophagitis
Precipitation of thyroid eye disease
Submit answer
Reference ranges v
Q35
A 33-year-old female is referred to endocrinology with thyrotoxicosis.

Following a discussion of management options she elects to have
radioiodine therapy. Which one of the following is the most likely
adverse effect?
I Hypothyroidism
Thyroid malignancy
Agranulocytosis
Oesophagitis
Precipitation of thyroid eye disease
It is well documented that radioiodine therapy can precipitate thyroid

eye disease but a majority of patients will eventually require thyroxine
replacement
"' 'f t9 Discuss (3) Improve ]
Next question )
Graves• disease: management
Despite many trials there is no clear guidance on the optimal

management of Graves' disease. Treatment options include titration of
anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace
regimes, radioiodine treatment and surgery. Propranolol is often given
initially to block adrenergic effects
ATD titration
• carbimazole is started at 40mg and reduced gradually to maintain
euthyroidism
• typically continued for 12-18 months
• patients following an ATD titration regime have been shown to
suffer fewer side-effects than those on a block-and-replace
regime
Block-and-replace
• carbimazole is started at 40mg
• thyroxine is added when the patient is euthyroid
• treatment typically lasts for 6-9 months
The major complication of carbimazole therapy is agranulocytosis
Radioiodine treatment
• contraindications include pregnancy (should be avoided for 4-6
months following treatment) and age< 16 years. Thyroid eye
disease is a relative contraindication, as it may worsen the
condition
• the proportion of patients who become hypothyroid depends on
the dose given, but as a rule the majority of patient will require
thyroxine supplementation after 5 years
Next question )
Q36
A 54-year-old man with type 2 diabetes mellitus is started on exenatide.

Which one of the following statements regarding exenatide is
incorrect?
Typically results in weight loss
May be combined with a sulfonylurea
The major adverse effect is flu-like symptoms
May be combined with metformin
Must be given by subcutaneous injection
Submit answer
Reference ranges v
The major adverse effect is flu-like symptoms
May be combined with metformin
Must be given by subcutaneous injection
Exenatide causes vomiting

Importance: 50
The major adverse effect is nausea and vomiting
8' •t tt Discuss (4) Improve
Next question )

glucagon-like peptide-1 (GLP-1 ), a hormone released by the small
Whilst it is well known that insulin resistance and insufficient B-cell


Glucagon-like peptide-1 (GLP-1) mim etics (e.g. exenatide)
mim etic.
Exenatide is an example of a gluca gon- like peptide-1 (GLP-1)
tion.
These drugs increase insulin secretion and inhib it gluca gon secre
ally
One of the majo r advances of GLP-1 mim etics is that they typic
insulin,
result in weig ht loss, in cont rast to man y med icatio ns such as
in
sulfonylureas and thiaz olidin edion es. They are some time s used
comb inatio n with insulin in T2DM to minim ise weig ht gain.
minu tes
Exenatide mus t be given by subc utan eous injec tion withi n 60
after a
before the morn ing and evening mea ls. It shou ld not be given
meal.
the main
Liraglutide is the othe r GLP-1 mim etic curre ntly available. One
be given
advantages of liraglutide over exenatide is that it only needs to
once a day.
n and a
Both exenatide and lirag lutide may be comb ined with metf ormi
used
sulfonylurea. Standard release exenatide is also licensed to be
for a
with basal insulin alone or with metf ormi n. Please see the BNF
more comp lete list of licensed indication s.
NICE state the follow ing:
Consider adding exenatide to metf ormi n and a su/fony/urea if•

• BMI >= 35 kg/ m in people of European desc ent and there are
2
prob lems associated with high weight, or

• BMI < 35 kg/ m and insulin is unacceptable because of
2
occu patio nal impli catio ns or weig ht Joss woul d bene fit othe r
comorbidities.
HbA 1c and 3% weight loss after 6 months to justify the ongoing

Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points

Next question )
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Q37
A 36-year-old female with a BMI of 34 kg/m"2 is reviewed after

managing to lose 3 kg in the past month. She asks about the possibility
of starting a drug to help her lose weight. What is the primary mode of
action of orlistat?
Leptin antagonist
Pancreatic lipase inhibitor
Prevents intestinal absorption of low-density lipoproteins
HMG-CoA reductase inhibitor
Centrally-acting appetite suppressant
Submit answer
Reference ranges v
Pancreatic lipase inhibitor
Prevents intestinal absorption of low-density lipoproteins
HMG-CoA reductase inhibitor
Centrally-acting appetite suppressant
Orlistat works by jnhibiting gastric and pancreatic lipase to reduce

the digestion of fat
Importance: 50
The primary mode of action of orlistat is to inhibit pancreatic lipases,

which in turn will decrease the absorption of lipids from the intestine
[ ,. •t - Discuss (1) Improve ]
I
Next question )
Next question )
Obesity: therapeutic options
The management of obesity consists of a step-wise approach:

• conservative: diet, exercise
• medical
• surgical
Orlistat is a pancreatic lipase inhibitor used in the management of

obesity. Adverse effects include faecal urgency/ incontinence and
flatulence. A lower dose version is now available without prescription
('Alli'). NICE have defined criteria for the use of orlistat. It should only be
prescribed as part of an overall plan for managing obesity in adults who
have:
• BMI of 28 kg/ m"2 or more with associated risk factors, or
• BMI of 30 kg/ m"2 or more
• continued weight loss e.g. 5% at 3 months
• orlistat is normally used for< 1 year
Next question )
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Q38
A 72-year-old man is reviewed in the diabetes clinic. He has a history of

heart failure and type 2 diabetes mellitus. His current medications
include furosemide 40mg od, ramipri l 10mg ad and bisoprolol 5mg ad.
Clinical examination is unremarkable with no evidence of peripheral
oedema, a clear chest and blood pressure of 130/ 76 mm Hg. Recent
renal and liver function tests are normal. Which one of the following
medications is contraindicated?
Sitagliptin
Pioglitazone
Gliclazide
Exenatide
Metformin
Submit answer
Reference ranges v
Pioglitazone
Gliclazide
Exenatide
Metformin
Pioglitazone - contraindicated by: heart failure

Importance: 50
Thiazolidinediones are absolutely contraindicated in heart failure
9' 11
f tt Discuss (2) Improve
Next question >

0 Q39
A 45-year-old woman is investigated for weight gain. She had had been
unwell for around four months and described a combination of
symptoms including depression, facial male-pattern hair growth and
reduced libido. During the work-up she was found to be hypertensive
with a blood pressure of 170/ 100 mmHg. Which one of the following
tests is most likely to be diagnostic?
Renin:aldosterone levels
High-dose dexamethasone suppression test
Pelvic ultrasound
Overnight dexamethasone suppression test
24 hr urinary free cortisol
Submit answer
Reference ranges v
24 hr urinary free cortisol
The overnight dexamethasone suppression test is the best test to

diagnosis Cushing's syndrome
Importance: 50
This patient has Cushing's syndrome as evidenced by the weight gain,

hirsutism, depression and hypertension. Polycystic ovarian syndrome
may give some of these features but would not cause such an elevated
blood pressure.
[ ,t 'f - Discuss (1 D) Improve
'
Next question >
Investigations are divided into confirming Cushing's syndrome and then

differentiate between true Cushing's and pseudo-Cushing's

Localisation tests
Localisation tests
The first-line localisation is 9am and midn ight plasma ACTH (and
t
corti sol) levels. If ACTH is suppressed then a non-ACTH dependen
be
Both low- and high-dose dexamethasone suppression tests may
. These
used to localise the path olog y resulting in Cushing's syndrome
tests may be interpreted as follow s:

dexamethasone prim ary causes, i.e. likely seco ndar y
to corti coste roid therapy


CRH stimu lation

• if pituitary source then corti sol rises
• if ectopic/adrenal then no change in corti sol
Petrosal sinus sampling of ACTH may be needed to diffe renti ate

between pituit ary and ecto pic ACTH secretion
Next ques tion )

Q40
Which one of the following may be associated wit h galactorrhoea?
Primary hypothyroidism
Addison's disease
Cushing's syndrome
Grave's disease
Bromocriptine
Submit answer
Reference ranges v
Q40
Which one of the following may be associated with galactorrhoea?
Primary hypothyroidism
Addison's disease
Cushing's syndrome
Grave's disease
Bromocriptine
[ ,t •• tt Discuss (3) Improve
Next question)
Prolactin and galactorrhoea
Prolactin is secreted by the anterior pituitary gland with release being

controlled by a wide variety of physiological factors. Dopamine acts as
the primary prolactin releasing inhibitory factor and hence dopamine
agonists such as bromocriptine may be used to control galactorrhoea.
It is important to differentiate the causes of galactorrhoea (due to the
actions of prolactin on breast tissue) from those of gynaecomastia
Features of excess prolactin

• men: impotence, loss of libido, galactorrhoea
• women : amenorrhoea, galactorrhoea
Causes of raised prolactin

• prolactinoma
• pregnancy
• oestrogens
• physiological: stress, exercise, sleep
• acromegaly: 1/ 3 of patients
• polycystic ovarian syndrome
• primary hypothyroidism (due to thyrotrophin releasing hormone
(TRH) stimulating prolactin release)
Drug causes of raised prolactin

• metoclopramide, domperidone
• phenothiazines
• haloperidol
• very rare: SSRls, opioids
Next question >

Q41
Each one of the following is a feature of pseudohypoparathyroidism,

except:
Short fourth and fifth metacarpals
Round face
Normal calcium and phosphate levels
Cognitive impairment
Short stature
Submit answer
Reference ranges v
Round face
Normal calcium and phosphate levels
Cognitive impairment
Short stature
[ •• •• ,_ Discuss Improve ]
Next question )
Pseudohypoparathyroidism
Pseudohypoparathyroidism is caused by target cell insensitivity to

parathyroid hormone (PTH) due to a mutation in a G-protein. In type I
pseudohypoparathyroidism
there is a complete receptor defect whereas in type II the cell receptor is
intact. Pseudohypoparathyroidism is typically inherited in an autosomal
dominant fash ion*
Bloods
• PTH: high
• calcium: low
• phosphate: high
Features
• short fourth and fifth metacarpals
• short stature
• cognitive impairment
• obesity
• round face
Investigation
• infusion of PTH followed by measurement of urinary phosphate
and cAMP measurement - this can help differentiate between type
I (neither phosphate or cAMP levels rise) and II (cAMP rises but
phosphate levels do not change)
*it was previously thought to be an X-linked dominant condition
Next question )
01
Which one of the following is the most common non-iatrogenic cause

of Cushing's syndrome?
Ectopic ACTH production
Adrenal adenoma
Micronodular adrenal dysplasia
Adrenal carcinoma
Pituitary tumour
Submit answer
Reference ranges v
I ~ou_r____
Pituit ary tu_m
Cushing's disease is the most comm on, non-iatrogenic, cause of

Cushing's syndrome
[ ,t ,. t9 Discuss (5) Impro ve ]
Next ques tion )
Cushing's syndrome: causes
It should be noted that exogenous cause s of Cushing's syndr ome ( e.g.

gluco cortic oid therapy) are far more comm on than endo geno us ones.
ACTH dependent causes

• Cushing's disease (80%) : pituit ary tumo ur secre ting ACTH
produ cing adrenal hyperplasia
• ectop ic ACTH produ ction (5-10%): e.g. small cell lung canc er
ACTH indep ende ntcau ses

• iatrogenic: stero ids
• adrenal adenoma (5-10%)
• adrenal carcin oma (rare)
• Carney comp lex: syndr ome includ ing cardi ac myxo ma
• micro nodu lar adrenal dyspl asia (very rare)
Pseudo-Cushing 's
• mimi cs Cushing's
• often due to alcoh ol excess or severe depression
• causes false positi ve dexam ethas one suppr essio n test or 24 hr
urinary free cortis ol
• insulin stress test may be used to differ entia te
Next uestio n )
Q2
A 42-year-old woman presents to the GP with a 6-week history of

constipation, lethargy and cold intolerance. She tells you that these
symptoms are much the same as when was diagnosed with
hypothyroidism five years ago. Since then, she has been established on
a dose of levothyroxine 75 micrograms once daily.
She reports starting a new medication 8 weeks ago, but is unable to

recall what it was called .
Of the following, which is most likely to be the medication that the

patient has recently started?
Cholecalciferol
Ferrous sulphate
Leveti ra ceta m
Metronidazole
Sertraline
Submit answer
Reference ranges v
I Ferrous sulphate
Levetiracetam
Metronidazole
Sertraline
Iron / calcium carbonate tablets can reduce the absorption of

levothyroxine - should be given 4 hours apart
Importance: 50
Iron (ferrous sulphate and ferrous fumarate) and calcium carbonate

tablets can reduce the absorption of levothyroxine.
This interaction is be a common reason why patients do not respond to

increasing doses of levothyroxine (especially in the exam setting!).
The BNF recommends that these medications should be given at least

4 hours apart.
The remaining medications are not known to interact with

levothyroxine.
[ •• •• • Discuss Improve ]
Next question )
Key points
be checked after 8-1 2 weeks
TSH in this range

Interactions
apart
*source: NICE Clinical Knowledge Summaries

Q3
What chromosome abnormality is associated with Klinefelter's

syndrome?
47, XO
47, XXV
46, XXV
47, XYY
47, xxo
Submit answer
Reference ranges v
47, XXV
46, XXV
47, XYY
47, xxo
Klinefelter's - 47, XXY

Importance: 50
,t 'f - Discuss Improve ]
Next question >
Klinefelter's syndrome is associated with karyotype 47, XXY.
Features
• often taller than average
• lack of secondary sexual characteristics
• small, firm testes
• infertile
• gynaecomastia - increased incidence of breast cancer
• elevated gonadotrophin levels but low testosterone
Diagnosis is by karyotype (chromosomal analysis).
Next question )
Q4
A 65-year-old man with a background of chronic obstructive pulmonary

disease, rheumatoid arthritis and polymyalgia rheumatica presents with
difficulty in climbing the stairs, worsening bruising on his arms and
weight gain. These symptoms have been progressively getting worse
and he is concerned whether it could be due to the fact that he has
been taking long term steroids for his underlying conditions. He is
aware of the sick-day rules which he reports adhering to and denies
ever stopping his treatment.
If a venous blood gas was to be performed on this patient you would

most likely find which of the following?
Mixed metabolic acidosis
Submit answer
Mixed metabolic acidosis

Importance: 50
This patient has symptoms suggestive of Cushing's syndrome caused

by prolonged exposure to exogenous corticosteroids such as
Prednisolone for his medical conditions.
Cushing 's syndrome - hypokalaemic metabolic alkalosis. The metabolic

alkalosis is due to excess aldosterone which increases acid and
potassium excretion in the kidney.
Addison's disease - hyperkalaemic metabolic acidosis. The metabolic

acidosis is due to insufficiency of aldosterone which decreases acid
secretion in the kidney and leads to the retention of potassium.
,. ,. • Discuss Improve ]
Next question )
I
Q5
A 54-year-old man is reviewed shortly after being diagnosed with

hypertension. as part of his work-up he had a series of blood tests to
screen for other risk factors:
Na+ 142 mmol/ I
K+ 3.9 mmol/ 1
Urea 6.2 mmol/ 1
Creati nine 91 µmol/1
Fasting glucose 7.7 mmol/1
Total cholesterol 7.2 mmol/1
Based on the fasting glucose result you arrange a HbA1 c:
HbA1 c 31 mmol/ mol (5.0%)
Which one of the following would explain the discrepancy between the
HbA1c and fasting glucose levels?
Vitamin 812 deficiency
Conn's syndrome
Raised cholesterol level
Sickle-cell anaemia
A history of alcohol excess
Submit answer
R81S€0 Cl IOIESLEIOI IEVEI
Sickle-cell anaemia
A history of alcohol excess
"' •t tt Discuss (3) Improve
Next question )
Glycosylated haemoglobin
Glycosylated haemoglobin (HbA1c) is the most widely used measure of

long-term glycaemic control in diabetes mellitus. HbA 1c is produced by
the glycosylation of haemoglobin at a rate proportional to the glucose
concentration. The level of HbA1c therefore is dependant on
• red blood cell lifespan
• average blood glucose concentration
A number of conditions can interfere with accurate HbA1c

interpretation:
Lower-than-expected levels of Higher-than-expected levels of

HbA1c (due to reduced red HbA1c (due to increased red
blood cell lifespan) blood cell lifespan)
Sickle-cell anaemia Vitamin B12/ folic acid

GP6D deficiency deficiency
Hereditary spherocyt osis Iron-deficiency anaemia
Splenectomy
,, • • t
HbA 1c is generally thought to reflect the blood glucose over the
previous '3 months' although there is some evidence it is weighed more
strongly to glucose levels of the past 2-4 weeks. NICE recommend
'HbA 1c should be checked every 3-6 months until stable, then 6 monthly'.
The relationship between HbA1c and average blood glucose is complex

but has been studied by the Diabetes Control and Complications Trial
(DCCT). A new internationally standardised method for reporting HbA 1c
has been developed by the International Federation of Clinical
Chemistry (IFCC). This will report HbA1c in mmol per mol of
haemoglobin without glucose attached.
HBA1c Average plasma glucose

(%) (mmol/1) IFCC-HbA1 c (mmol/mol)
5 5.5
6 7 .5 42
7 9 .5 53
8 11 .5 64
9 13.5 75
10 15.5
11 17.5
12 19.5
From the above we can see that average plasma glucose = (2 * HbA1c)
-4.5
Q6
A 50 year-old woman presents with polyuria and polydipsia. She has

recently been started on cita lopram for depression, but is otherwise fit
and well. She has complained of constipation recently, but has put this
down to her new medication.
Calcium 2.8mmol/l
Phosphate 0.7mmol/l
Parathyroid hormone 5.0pmol/I (1.2-5.Bpmol/ l)
Renal function and ful l blood count are normal.
What is the most likely cause for these blood results?
Parathyroid adenoma
Myeloma
Metastatic cancer
Drug induced
Parathyroid hyperplasia
Submit answer
Parathyroid adenoma
Myeloma
Metastati c cancer
Drug induced
Parathyroid hyperplasia
The PTH level in primary hyperparathyroidism may be normal

Importance: 50
This woman has signs and symptoms of hypercalcaemia. Her

parathyroid hormone should be suppressed in the presence of
hypercalcaemia. Given that it is normal (inappropriately), this indicates
the parathyroid as the cause for the hypercalcaemia. The most
common cause of hyperparathyroidism is an adenoma.
11• 11f ta Discuss (7) Improve
Next question )
Primary hyperparathyroidism
In exams, primary hyperparathyroidism is stereotypically seen in elderly

females with an unquenchable thirst and an inappropriately normal or
raised parathyroid hormone level. It is most commonly due to a solitary
adenoma
Causes of primary hyperparathyroidism

• 80%: solitary adenoma
• 15%: hyperplasia
• 4%: multiple adenoma
• 1%: carcinoma
Features - 'bones, stones, abdominal groans and psychic moans'
• polydipsia, polyuria
• peptic ulceration/constipation/pancreatitis
• bone pain/ fracture
• renal stones
• depression
• hypertension
Associations
• hypertension
• multiple endocrine neoplasia: MEN I and II
Investigations
• raised calcium, low phosphate
• PTH may be raised or (inappropriately, given the raised calcium)
normal
• technetium-MIBI subtraction scan
• pepperpot skull is a characteristic X-ray finding of
hyperparathyroidism
Treatment
• the definitive management is total parathyroidectomy
• conservative management may be offered if the calcium level is
less than 0.25 mmol/L above the upper limit of normal AND the
patient is > 50 years AND there is no evidence of end-organ
damage
• calcimimetic agents such as cinacalcet are sometimes used in
patients who are unsuitable for surgery
Bilateral hand radiographs in a middle-aged woman
demonstrating generalised osteopenia, erosion of the terminal
phalangeal tufts (acro-osteolysis) and subperiosteal resorption
of bone particularly the radial aspects of the 2nd and 3rd middle
phalanges. These changes are consistent with a diagnosis of
hyperparathyroidism.
Q7
A 33-year-old woman presents with weight loss and excessive

sweating. her partner reports that she is 'on edge' all the time and
during the consultation you notice a fine tremor. Her pulse rate is
96/min. A large, non-tender goitre is noted. Examination of her eyes is
unremarkable with no evidence of exophthalmos.
Free T 4 26 pmoVI
Free T3 12.2 pmol/1 (3.0-7.5)
TSH < 0.05 mu/ I
Toxic multinodular goitre
Hashimoto's thyroiditis
T3-secreting adenoma
De Quervain's thyroiditis
Graves' disease
Submit answer
Graves a1sease
Graves' disease is the most common cause of thyrotoxicosis

Importance: 50
Only around 30% of patients with Graves' disease have eye disease so
the absence of eye signs does not exclude the diagnosis.
16 11
Next question )
Graves' disease: features
Graves' disease is the most common cause of thyrotoxicosis. It is

typically seen in women aged 30-50 years.
Features
• typical features of thyrotoxicosis
• specific signs limited to Grave's (see below)
Features seen in Graves' but not in other causes of thyrotoxicosis

• eye signs {30% of patients)
o exophthalmos
o ophthalmoplegia
• pretibial myxoedema
• thyroid acropachy, a triad of:
o digital clubbing
o soft tissue swelling of the hands and feet
o periosteal new bone formation
Autoantibodies
• TSH receptor stimulating antibodies {90%)
• anti-thyroid peroxidase antibodies (75%)
Q8
A 25-year-old female has type I diabetes. Her HbA 1c is 58 mmol/L. Her

blood pressure is 126/68 mmHg. Her BMI is 28 kg/m 2 • She is using a
basal-bolus regimen which she finds easy to manage. She is not keen to
increase her total insulin dose. Which of the following adjuncts could
you consider to help improve her glycaemic control?
Add metformin
Switch to a mixed insulin regime
Add sitagliptin
Add exenatide
Enrol in supported weight loss programme
Submit answer
Reference ranges v
A 25-year-old female has type I diabetes. Her HbA 1c is 58 mmol/ L. Her
blood pressure is 126/ 68 mmHg. Her BMI is 28 kg/m 2 • She is using a
basal-bolus regimen which she finds easy to manage. She is not keen to
increase her total insulin dose. Which of the following adjuncts cou ld
you consider to help improve her glycaemic control?
I Add metformin
,---------
Switch to a mixed insulin regime
Add sitagliptin
Add exenatide
Enrol in supported weight loss programme
Patients with type I diabetes and a BMI > 25 should be considered

for metformin in addition to insulin
Importance: 50
The correct answer is to add metformin. NICE recommends that adding

metformin should be considered in type I diabetics with a BMI > 25,
either on patient preference or to avoid the need to increase t heir insulin
therapy. The other oral diabetic medications are not currently
recommended. Weight loss is likely to be beneficial but there is greater
evidence for benefit with the use of metformin. A mixed insulin regime
might be used if a multiple injection basal-bolus regime was not suited
to the patient's lifestyle but is not usually chosen for better glycaemic
control.
NICE: Tvoe I diabetes in adults

The long-term management of type 1 diabetics is an important and

complex process requiring the input of many different clinical
specialties and members of the healthcare team. A diagnosis of type 1
diabetes can still reduce the life expectancy of patients by 13 years and
the micro and macrovascular complications are well documented.
NICE released guidelines on the diagnosis and management of type 1

diabetes in 201 5. We've only highlighted a very select amount of the
guidance here which will be useful for any clinician looking after a
patient with type 1 diabetes.
HbA1c
• should be monitored every 3-6 months
• adults should have a target of HbA1c level of 48 mmol/mol (6.5%)
or lower. NICE do however recommend taking into account factors
such as the person's daily activities, aspirations, likelihood of
complications, comorbidities, occupation and history of
hypoglycaemia
Self-monitoring of blood glucose

• recommend testing at least 4 times a day, including before each
meal and before bed
• more frequent monitoring is recommended if frequency of
hypoglycaemic episodes increases; during periods of illness;
before, during and after sport; when planning pregnancy, during
pregnancy and while breastfeeding
Blood glucose targets

• 5-7 mmol/I on waking and
• 4-7 mmol/I before meals at other times of the day
Type of insulin
• offer multiple daily injection basal-bolus insulin regimens, rather
than twice-daily mixed insulin regimens, as the insulin injection
regimen of choice for all adults
• twice-daily insulin detemir is the regime of choice. Once-daily
insulin glargine or insulin detemir is an alternative
• offer rapid-acting insulin analogues injected before meals, rather
than rapid-acting soluble human or animal insulins, for mealtime
insulin replacement for adults with type 1 diabetes
Metformin
• NICE recommend considering adding metformin if the BMI >= 25
kg/ m 2
Next question )
-------------------------------
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~ 1- --
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Q1
A 27-year-old female develops eye pain and reduced visual acuity

following the initiation of treatment for her recently diagnosed Grave's
disease. Which one of the following treatments is likely to have been
started?
Thyroidectomy
Propylthiouracil
Carbimazole and thyroxine
Carbimazole
Submit answer
Reference ranges v
Thyroidectomy
Propylthiouracil
Carbimazole and thyroxine
Carbimazole
Radioiodine treatment may lead to the development/ worsening of

thyroid eye disease in up to 15% of patients with Grave's disease
Next question )
Thyroid eye disease
Thyroid eye disease affects between 25-50% of patients with Graves'

disease.
Pathophysiology
• it is thought to be caused by an autoimmune response against an
autoantigen, possibly the TSH receptor - retro-orbital
inflammation
• the inflammation results in glycosaminoglycan and collagen
deposition in the muscles
Prevention
• smoking is the most important modifiable risk factor for the
development of thyroid eye disease
• radioiodine treatment may increase the inflammatory symptoms
seen in thyroid eye disease. In a recent study of patients with
Graves' disease around 15% developed, or had worsening of, eye
disease. Prednisolone mav help reduce the risk
Features
• the patient may be eu-, hypo- or hyperthyroid at the time of
presentation
• exophthalmos
• conjunctiva! oedema
• optic disc swelling
• ophthalmoplegia
• inability to close the eyelids may lead to sore, dry eyes. If severe
and untreated patients can be at risk of exposure keratopathy
Management
• topical lubricants may be needed to help prevent corneal
inflammation caused by exposure
• steroids
• radiotherapy
• surgery
Monitoring patients with established thyroid eye disease
For patients with established thyroid eye disease the following

symptoms/signs should indicate the need for urgent review by an
ophthalmologist (see EUGOGO guidelines):
• unexplained deterioration in vision
• awareness of change in intensity or quality of colour vision in one
or both eyes
• history of eye suddenly 'popping out' (globe subluxation)
• obvious corneal opacity
• cornea still visible when the eyelids are closed
• disc swelling
Next question >

Q1
Which one of the following drugs used in the management of type 2

diabetes mellitus has the Medicines and Healthcare products
Regulatory Agency warned is associated with an increased risk of
severe pancreatitis and renal impairment?
Rosiglitazone
Metformin
Acarbose
Exenatide
Sitagliptin
Submit answer
Reference ranges v
I Exenatide -~-- ---- ---'
Sitagliptin
[ ,6 •• • Discuss (4) Improve ]
Next quest ion )
A number of new drugs to treat diabetes mellit us have becom e

glucagon-like peptide-1 {GLP-1 ), a horm one released by the small
Whilst it is well known that insulin resistance and insuff icient B-cell
compensation occur other effect s are also seen in type 2 diabe tes
this known as the incretin effect. This effec t is largely mediated by GLP-
1 and is known to be decreased in T2DM .

(glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibi ting

One of the major advances of GLP-1 mimetics is that they typically
result in weight loss, in contrast to many medications such as insulln,
sulfonylureas and thiazolidinediones. They are sometimes used in

meal.
once a day.
Both exenatide and liraglutide may be combined with metformin and a

with basal insulin alone or with metformin. Please see the BNF for a
Consider adding exenatide to metformin and a sulfonylurea if

occupational implications or weight loss would benefit other
comorbidities.
I

HbA1c and 3% weight loss after 6 months to justify the ongoing

Dipeptidyl peptidase-4 {DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points

Next question )
Save my notes
Q2
A 32-year-old woman who is 24 weeks pregnant with her third child

comes to the clinic for review. She has been diagnosed with gestational
diabetes mellitus, and a fasting plasma glucose following 2 weeks of
adherence to lifestyle changes is still elevated at 6.8 mmol/1. Her blood
pressure is 122/82 mmHg, and her body mass index is 25 kg/m 2 • She is
reluctant to start insulin initially because her sister has Type 1 diabetes
and suffers from frequent hypoglycaemia.
Which of the following is the most appropriate next intervention?
Metformin
Glibenclamide
Insulin glargine
Dapagliflozin
Insulin pump therapy
Submit answer
Reference ranges v
Glibenclamide
Insulin glargine
Dapagllflozin
Insulin pump therapy
Metformin is the first line therapy of choice for diabetes in

pregnancy
Importance: 50
Metformin has been evaluated in a large Australasian trial for the

treatment of gestational diabetes mellitus. Versus insulin initiation at
the point of diagnosis, those patients treated with metformin gained
less weight during pregnancy and suffered slightly fewer episodes of
hypoglycaemia. There was no difference in the primary endpoint of
adverse foetal outcomes, and women treated with metformin first
preferred this option, even though most eventually progressed to insulin
in addition to oral therapy. This has precipitated NICE to recommend
metformin as a first line option where fasting glucose is less than 7.0
mmol/I despite dietary modification.
https://www.nejm.org/ doi/ full/10.1056/ NEJMoa0707193

https://www.nice.org.uk/guidance/ng3
Although glibenclamide is safe in pregnancy it does not limit weight

gain and control is inferior to insulin therapy. It's therefore only an
option in patients who refuse metformin and insulin. Out of the insulin
options listed, insulin pump therapy is preferred, although many women
find it more difficult to comply with pump therapy and are therefore
treated with a basal bolus regimen. There is no evidence to support the
use of SGLT-2 inhibitors such as dapagliflozin in pregnancy. One
problem which leads to diabetes is relative insulin resistance, which
SGLT-2 inhibitors will not significantly impact upon.
Next question ~
Pregnancy: diabetes mellitus
Diabetes mellitus may be a pre-existing problem or develop during

pregnancy, gestational diabetes. It complicates up to 1 in 20
pregnancies. NICE estimate the following breakdown:
• 87.5% have gestational diabetes
• 7.5% have type 1 diabetes
• 5% have type 2 diabetes
Risk factors for gestational diabetes

• BMI of> 30 kg/m 2
• previous macrosomic baby weighing 4.5 kg or above
• previous gestational diabetes
• first-degree relative with diabetes
• family origin with a high prevalence of diabetes (South Asian,
black Caribbean and Middle Eastern)
Screening for gestational diabetes

• women who've previously had gestational diabetes: oral glucose
tolerance test (OGTT) should be performed as soon as possible
after booking and at 24-28 weeks if the first test is normal. NICE
also recommend that early self-monitoring of blood glucose is an
alternative to the OGTTs
• women with any of the other risk factors should be offered an
OGTT at 24-28 weeks
Diagnostic thresholds for gestational diabetes

• these have recently been updated by NICE, gestational diabetes is
diagnosed if either:
• fasting glucose is >= 5.6 mmol/1
• 2-hour glucose is >= 7.8 mmol/1
Management of gestational diabetes
• newly diagnosed women should be seen in a Joint diabetes and
antenatal clinic within a week
• women should be taught about selfmonitoring of blood glucose
• advice about diet (including eating foods with a low glycaemic
index) and exercise should be given
• if the fasting plasma glucose level is < 7 mmol//I a trial of diet and
exercise should be offered
• if glucose targets are not met within 1-2 weeks of altering
diet/ exercise metformin shou ld be started
• if glucose targets are still not met insulin should be added to
diet/ exercise/ metformin
• if at the time of diagnosis the fasting glucose level is >= 7 mmol/I
insulin should be started
• if the plasma glucose level is between 6-6.9 mmol/I, and there is
evidence of complications such as macrosomia or hydramnios,
insulin should be offered
• glibenclamide should only be offered for women who cannot
tolerate metformin or those who fail to meet the glucose targets
with metformin but decline insulin treatment
Management of pre-existing diabetes

• weight loss for women with BMI of> 27 kg/m"2
• stop oral hypoglycaemic agents, apart from metformin, and
commence insulin
• folic acid 5 mg/ day from pre-conception to 12 weeks gestation
• aspirin 75mg/day from 12 weeks until the birth of the baby, to
reduce the risk of pre-eclampsia
• detailed anomaly scan at 20 weeks including four-chamber view
of the heart and outflow tracts
• tight glycaemic control reduces complication rates
• treat retinopathy as can worsen during pregnancy
CamScanne, -? Y.¥-> i.b. ~I

Targets for self monitoring of pregnant women (pre-existing and
gestational diabetes)
Time Target
Fasting 5.3 mmol/I
1 hour after meals 7.8 mmol/I, or:
2 hour after meals 6.4 mmol/I
Next question )
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Search
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Q Google search on "Pregnancy: diabetes mellitus''
Links
Q3
What is the mechanism of action of thiazolidinediones?
PPAR-gamma receptor antagonist
PPAR-alpha receptor antagonist
PPAR-alpha receptor agonist
PPAR-gamma receptor agonist
Increases endogenous insulin secretion
Submit answer
Reference ranges v
PPAR-gamma receptor agonist
Increases endogenous insulin secretion
Glitazones are agonists of PPAR-gamma receptors, reducing

peripheral insulin resistance
Importance: 50
116 •• tit Discuss Improve
Next question )
Thiazolidinediones
Thiazolidinediones are a class of agents used in the treatment of type 2

diabetes mellitus. They are agonists to the PPAR-gamma receptor and
reduce peripheral insulin resistance. Rosiglitazone was withdrawn in
201 O following concerns about the cardiovascular side-effect profile.

natural ligands are free fatty acids and it is thought to control adipocyte
differentiation and function.
Adverse effects
• weight gain
• fluid retention - therefore contraindicated in heart failure. The risk
• recent studies have indicated an increased risk of fractures
bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
A 29-year-old female who is 7 weeks into her first pregnancy is
investigated for excessive sweating and tremor. Blood tests reveal the
following:
TSH < 0.05 mu/ I
T4 188 nrnol/1
What is the most appropriate management?
Immediate surgery
Carbimazole
Surgery at start of third trimester
Propylthiouracil
Radioiodine
Submit answer
Reference ranges v
Propylthiouracil
Radioiodine
According to CKS:
Propy/thiouraci/ is used in the first trimester of pregnancy in place

of carbimazole, as the latter drug may be associated with an
increased risk of congenital abnormalities. At the beginning of the
second trimester, the woman should be switched back to
carbimazole, as propylthiouraci/ has been associated with a small
risk of severe hepatic injury
[ ,6 •• tt Discuss Improve ]
Next question )
Pregnancy: thyroid problems
In pregnancy, there is an increase in the levels of thyroxine-binding

globulin (TBG). This causes an increase in the levels of total thyroxine
but does not affect the free thyroxine level.
Thyrotoxicosis
Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart

failure and premature labour
Graves' disease is the most common cause of thyrotoxicosis in
pregnancy. It is also recognised that activation of the TSH receptor by
HCG may also occur - often termed transient gestational
hyperthyroidism. HCG levels will fall in the second and third trimester
Management
• propylthiouracil has traditionally been the antithyroid drug of
choice
• however, propylthiouracil is associated with an increased risk of
severe hepatic injury
• therefore NICE Clinical Knowledge Summaries advocate the
following : 'Propylthiouracil is used in the first trimester of pregnancy
in place of carbimazole, as the latter drug may be associated with
an increased risk of congenital abnormalities. At the beginning of
the second trimester, the woman should be switched back to
carbimazole'
• maternal free thyroxine levels should be kept in the upper th ird of
the normal reference range to avoid fetal hypothyroidism
• thyrotrophin receptor stimulating antibodies should be checked at
30-36 weeks gestation - helps to determine the risk of neonatal
thyroid problems
• block-and-replace regimes should not be used in pregnancy
• radioiodine therapy is contraindicated
Hypothyroidism
Key points
• thyroxine is safe during pregnancy
• serum thyroid stimulating hormone measured in each trimester
and 6-8 weeks post-partum
• some women require an increased dose of thyroxine during
pregnancy
• breast feeding is safe whilst on thyroxine
Next question >

QS
Which one of the following statements regarding maturity-onset

diabetes of the young (MODY) is true?
There is usually a strong family history
Body mass index is typically > 30
Doesn't respond to glimepiride
Autosomal recessive inheritance
Frequent episodes of diabetic ketoacidosis are typical
Submit answer
Reference ranges v
QS
Which one of the following statements regarding maturity-onset

diabetes of the young (MODY) is true?
IThere is usually a strong family history
Body mass index is typically > 30
Doesn't respond to glimepiride
Frequent epi sodes of diabetic ketoacidosis are typical
116 11
f tt Discuss Improve
Next question )
MODY
Maturity-onset diabetes of the young (MODY) is characterised by the

development of type 2 diabetes mellitus in patients< 25 years old. It is
typically inherited as an autosomal dominant condition. Over six
different genetic mutations have so far been identified as leading to
MODY.
It is thought that around 1-2% of patients with diabetes mellitus have

MODY, and around 90% are misclassified as having either type 1 or type
2 diabetes mellitus.
MODY3
• 60% of cases
• due to a defect in the HNF-1 alpha gene
• is associated with an increased risk of HCC
MODY2
• 20% of cases
• due to a defect in the glucokinase gene
MODY 5
• rare
• due to a defect in the HNF-1 beta gene
• liver and renal cysts
Features of MODY
• typically develops in patients < 25 years
• a family history of early onset diabetes is often present
• ketosis is not a feature at presentation
• patients with the most common form are very sensitive to
sulfonylureas, insulin is not usually necessary
Q6
Which one of the following is not associated with primary

hyperparathyroidism?
Hypotension
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 2a
Depression
Pancreatitis
Submit answer
Reference ranges v
r Hypotension
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 2a
Depression
Pancreatitis
Primary hyperparathyroidism is associated with hypertension
" 'f tit Discuss (3) Improve ]
Next question )

adenoma

• 15%: hyperplasia
• 1%: carcinoma
• peptic ulceration/constipation/pancreatitis
• bone pain/fracture
• renal stones
• depression
• hypertension
Associations
• hypertension
Investigations
• raised call cium, low phosphate
• PTH may be raised or (inappropriately, given the raised calcium)
normal
hyperparathyroidism
Treatment
damage
Q7
A 61-year-old man presents as he developed enlargement of his breast

tissue. He has become very self-conscious and is worried about going
on holiday in the summer. Which one of the following drugs is most
likely to be responsible?
Amitriptyline
lsoniazid
Verapamil
Methyldopa
Spironolactone
Submit answer
Reference ranges v
lsoniazid
Verapamil
Methyl dopa
Spironolactone
All the above drugs may cause gynaecomastia but spironolactone is the
most common cause.
" •• _. Discuss (2) Improve ]
Next question )
Gynaecomastia
Gynaecomastia describes an abnormal amount of breast tissue in

males and is usually caused by an increased oestrogen:androgen ratio.
Causes of gynaecomastia
• physiological: normal in puberty
• syndromes with androgen deficiency: Kallman's, Klinefelter's
• testicular failure: e.g. mumps
• liver disease
• testicular cancer e.g. seminoma secreting hCG
• ectopic tumour secretion
• hyperthyroidism
• haemodialysis
• drugs: see below
Drug causes of gynaecomastia

• spironolactone (most common drug cause)
• cimetidine
• digoxin
• cannabis
• fmasteride
• gonadorelin analogues e.g. Goserelin, buserelin
• oestrogens, anabolic steroids
Very rare drug causes of gynaecomastia

• tricyclics
• isoniazid
• calcium channel blockers
• heroin
• busulfan
• methyldopa
Q8
A 35-year-old gentleman is followed up in general practice after a

routine health check at work has Identified high blood pressure. He has
been started on initial anti-hypertensive therapy whi lst awaiting
investigation. He is otherwise well with no past medical history of note.
He reports that his grandfather had been previously diagnosed with

Conn's syndrome at an early age.
Which of the following can interfere with testing for primary

hyperaldosteronism?
Digoxi n
Amlodipine
lvabradine
Bisoprolol
Ramipril
Submit answer
Reference ranges v
( Kam1prn
The answer here is ramipril. The reason behind this is due to its
interference with the renin-angiotensin-aldosterone system, for which
the other medications do not.
Medications that can cause false negative renin:aldosterone ratio

results are the following:
• Angiotensin-converting enzyme inhibitors (e.g. ramipril or
lisinopril).
• Angiotensin receptor blockers (e.g. losartan).
• Direct renin inhibitors (e.g aliskiren).
• Aldosterone antagonists (e.g. spironolactone or eplerenone).
a6 if t9 Discuss (5) Improve
Next question )
Primary hyperaldosteronism
Primary hyperaldosteronism was previously thought to be most

commonly caused by an adrenal adenoma, termed Conn's syndrome.
However, recent studies have shown that bilateral idiopathic adrenal
hyperplasia is the cause in up to 70% of cases. Differentiating between
the two is important as this determines treatment. Adrenal carcinoma is
an extremely rare cause of primary hyperaldosteronism.
Features
• hypertension
• hypokalaemia
o e.g. muscle weakness
o this is a classical feature in exams but studies suggest this
is seen in only 10-40% of patients
• alkalosis
Investigations
• the 2016 Endocrine Society recommend that a plasma
aldosterone/renin ratio is the first-line investigation in suspected
primary hyperaldosteronism
o should show high aldosterone levels alongside low renin
levels (negative feedback due to sodium retention from
aldosterone)
• following this a high-resolution CT abdomen and adrenal vein
sampling is used to differentiate between unilateral and bilateral
sources of aldosterone excess
• Adrenal Venous Sampling (AVS) can be done to identify the gland
secreting excess hormone in primary hyperaldosteronism
Management
• adrenal adenoma: surgery
• bilateral adrenocortical hyperplasia: aldosterone antagonist e.g.
spironolactone
Q9
A 68-year-old man attends his GP surgery for his chronic disease annual
review following on from recent blood tests.
His past medical history includes hypertension, polymyalgia rheumatica

and type 2 diabetes mellitus.
He regularly takes amlodipine, bendroflumethiazide, prednisolone on a

reducing regimen, sitagliptin and metformin.
M ale: (135-180)
Hb 142 g/ L
Female: (115 - 160)
Plat elets 270 * 109 / L (150 - 400)
WBC 12.8 * 109 / L (4.0 - 11 .0)
Neuts 10.6 * 109 / L (2.0 - 7.0)
Which Is his medications is the most likely cause of his raised

neutrophil count?
Amlodipine
Bendroflumethiazide
Metformin
Prednisolone
Sitagliptin
Submit answer
Cam Sconner ...,, ',&~ .G. ~ I

Bendroflumethiazide
Metformin
Prednisolone
Sitagliptin
Glucocorticoid treatment can induce neutrophilia

Importance: 50
Amlodipine and bendroflumethiazide can cause leucopenia, not

neutrophilia.
Sitagliptin and metformin don't affect leukocytes.
Prednisolone can cause neutrophilia through:

• Demargination of neutrophils via the endovascular lining.
• Delayed migration of neutrophils into tissue.
• Release of immature neutrophils from bone marrow.
During bacterial infection, there is an increased 'left shift' seen on

microscopy. In 'left shift' neutrophils are produced and released from
the bone marrow at an equal rate to their consumption in the
circulation.
With steroid use, 'left shift' generally does not occur due to increased
production and release of neutrophils from the bone marrow but no
neutrophil consumption.
9' 11
f tt Discuss Improve
Next question )
Next question )
Corticosteroids: side-effects
• endocrine: impaired glucose regulation, increased appetite/ weight
• dermatological: acne
• neutrophilia
• fluid retention
• hypertension
Next question )
B J I!! A • ·-
·- 1-
~
- - ...
Q10
A 25-year-old Asian woman who is 26 weeks pregnant has an oral

glucose tolerance test (OGTT). This was requested due t o a
combination of her et hnicit y and a background of obesity. A recent
ult rasound shows that the fetus is large for dates. The f ollowing results
are obtained:
0 9.2
2 14.2
What is the most appropriate management ?
Start insulin
Give advice about a diabetic diet
Give advice about a diabetic diet + repeat OGTT in 4 weeks
Start gliclazide
Start metformin
Submit answer
A L~-year-u1u Asian woman wno 1s zo weeKs pregnan1 nas an oral
glucose tolerance test (OGTT). This was requested due to a
combination of her ethnicity and a background of obesity. A recent
ultrasound shows that the fetus is large for dates. The following results
are obtained:
Time (hours) Blood glucose (mmol/ 1)
0 9.2
2 14.2
I Start insulin
Give advice about a diabetic diet
Give advice about a diabetic diet+ repeat OGTT in 4 weeks
Start gliclazide
Start metformin
Insulin should be started straight away given the blood glucose levels
and evidence of macrosomia. Aspirin should also be considered as she
is at increased risk of pre-eclampsia.
9' •• tt Discuss Improve
Next question )
Q11
A 50-year-old female complains that she has put on weight around her
abdomen and th ighs in the last six months. She has a past medical
history of hypertension, high cholesterol, type II diabetes and asthma.
She has not changed her diet or lifestyle during the last six months.
Which of her medications may be contributing to her weight gain?
Atorvastatin
Tolbutamide
Exenatide
Chlortalidone
Saxagliptin
Submit answer
Reference ranges v
Tolbutamide
Exenatide
Chlortalidone
Saxagliptin
Sulfonylureas often cause weight gain

Importance: 50
The correct answer is 2. Tolbutamide is a member of the sulfonylurea

class, which ar,e known to often cause weight gain because they
stimulate the pancreas to release more insulin, therefore allowing for
the utilisation of more glucose. The gliptins are not associated with
weight gain.
BNF
https://bnf.nice.org.uk/ treatment-summary/ type-2-diabetes.html
116 t
11 • Discuss (2) Improve
Next question >

Next question )
Sulfonylureas

On a molecular level they bind to an ATP-dependent K+(KATP) channel

• weight gain

secretion
Sulfonylureas should be avoided in breastfeeding and pregnancy.
Next question )
B I A .. 2.=
1- -_ ....
~ c-:::>
Q12
A 59-year-old woman comes to the diabetes clinic for review. Current

medication incJudes metformin and sitagliptin, but her HbA1 c has
continued to rise and additional therapy is required . Her body mass
index is 35 kg/ m 2 • Blood pressure is 132/ 82 mmHg, her pulse is 74
beats per minute and regular. A decision is made to start her on
degludec liraglutide combination therapy.
Which of the following should you warn her about?
Patients often get skin nodules around the injection site
Pancreatitis is commonly associated with treatment
Risk of hypoglycaemia will increase when she starts treatment
She will lose approximately 5kg in weight when she starts

treatment
She will gain approximately 6kg in the first year of treatment
Submit answer
Reference ranges v
rdlll,;lt:dllll::> I::> l,;UIIIIIIUIIIY d::>::>Ul,;ldlt:U VVILII llt:dllllt:lll
Risk of hypoglycaemia will increase when she starts treatment
She will lose approximately 5kg in weight when she starts treatment
She will gain approximately 6kg in the first year of treatment
insulin and GLP-1 fixed dose combinations are increasingly attractive as

a treatment option for diabetologists because they combine the potent
glucose-lowering effect of GLP-1 agonists and long-acting insulin
analogues in one preparation. They are however associated with
increased risk of hypoglycaemia, Rates of confirmed hypoglycaemia
(<3.1 mmol/I), run at between 1.8 and 3.5 per patient year of exposure.
Skin nodules are most often seen around injection sites when modified
release systems are used for delivering GLP-1, such as those used in
weekly exenatide, (microspheres). Pancreatitis features in case reports
associated with the use of GLP-1 agonists, although no consistent link
has been established. Modest weight loss is seen when patients start
degludec / liraglutide against a background of oral agents, but this is
less than that seen for patients who start liraglutide alone.
https://www.evidence.nhs.uk/formulary/bnf/current/6-endocrine-
system/61-drugs-used-in-diabetes/612-antidiabetic-drug s/6123-other-
antidiabetic-drugs
8' ,., t9 Discuss (8) Improve ]
Next question )
Next question )





meal.
once a day.


comorbidities.

HbA 1c and 3% weight loss after 6 months to justify the ongoing

Dipeptidyl peptidase-4 {DPP-4) inhibitors ( e.g. Vildagliptin, sitagliptin)
Key points
no increased incidence of hypoglycaem ia

thiazolidinedione if further weight gain wou ld cause significant
Next question )
B I
Save my n ates
Search
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■
Q13
An 81-year old female is admitted with a 6-week history dysphagia to

both solids and liquids. She describes odynophagia, weight loss and
night sweats.
On examination there was firm irregular mass in the right side of the
anterior triangle of the neck. It was fixed, cold and painless. The mass
moved with swallowing and you note a faint stridor like sound on
inspiration. There was a further 3 irregular lymph nodes of note on
palpation.
Bloods:
Thyroid stimulating hormone 4.5 mu/I
Free T4 12 pmol/1
Total T4 99 nmol/1
An ultrasound-guided biopsy is likely to reveal which histological

tumour?
Papillary
Follicular
Medullary
Anaplastic
Lymphoma
Ana plastic
Lymphoma
Anaplastic thyroid cancer is a highly aggressive, locally invasive tumour.

It typically presents in older patients with a rapidly increasing mass or
lymph node. Anaplastic tumours invades local surrounding tissues
causing compression symptoms including: pain, shortness of breath
and dysphagia. The aggression of the tumour often leads to
lymphovascular invasion and subsequent bone and lung metastasis.
The cancer originates from follicular cells, which are poorly
differentiated and have a high mitotic rate. The prognosis is poor with a
5-year survival rate quoted between 7% and 14%. Treatment is usually
palliative, with a combination of radiotherapy and chemotherapy.
11• 11 f tt Discuss (5) Improve
Next question )
Thyroid cancer

hormones
Main points
Type Percentage

prognosis
Follicular 20%


thyroiditis

Further information
Type Notes



adenoma.
adenoma.

carcinoma tissue
cases

Next question )
Save my notes
Q14
Which of the following is least recognised as a potential complication

of acromegaly?
Colorectal cancer
Hypertension
Cardiomyopathy
Diabetes mellitus
Pulmonary hypertension
Submit answer
Reference ranges v
I Pulmonary hype_r_te_n_s_io_n_ _ _ _ _~ .
Acromegaly is associated with systemic rather than pulmonary

hypertension.
Secondary causes of pulmonary hypertension include COPD, congenital

heart disease (Eisenmenger's syndrome), recurrent pulmonary
embolism, HIV and sarcoidosis.
16 11
Next question >
In acromegaly there is excess growth hormone secondary to a pituitary

adenoma in over 95% of cases. A minority of cases are caused by
ectopic GHRH or GH production by tumours e.g. pancreatic.
Features
• coarse facial appearance, spade-like hands, increase in shoe size
• large tongue, prognathism, interdental spaces
• excessive sweating and oily skin: caused by sweat gland
hypertrophy
• features of pituitary tumour: hypopituitarism, headaches,
bitemporal hemianopia
• raised prolactin in 1/ 3 of cases _... galactorrhoea
• 6% of patients have MEN-1
Complications
• hypertension
• diabetes (>10%)
• cardiomyopathy
• colorectal cancer
Q15 [CJ
A 58-year-old gentleman with longstanding type 2 diabetes presents to

the acute medical take. Blood tests are demonstrated in the table
below. The blood test results are consistent with diabetic ketoacidosis.
He has no other past medical history other than type 2 diabetes and
obesity. He has not had episodes of diabetic ketoacidosis before and
does not drink alcohol. His medication history includes aspirin, losartan,
metformin, dapagliflozin and glimepiride. He is allergic to penicillin.
pH 7.26
Blood ketones 3.6 mmol/ L
Blood sugar 15 mmol/ L
Which of his medications is most likely to have contributed to

developing diabetic ketoacidosis?
Metformin
Dapagliflozin
Glimepiride
Aspirin
Losartan
Submit answer
Dapagliflozin
Glimepiride
Aspirin
Losartan
Dapagliflozin is a newer drug for the treatment of diabetes. It is a

member of the sodium-glucose transport protein 2 (SGLT2) inhibitor
class of drugs.
SGLT2 inhibitors prevent the resorption of glucose from the proximal

renal tubule, resulting in more glucose being secreted in the urine.
The other medications in this class include: canagliflozin &

empagliflozin
Importantly, whilst these medications represent an effective class of

drugs, there are reports of patients with type 2 diabetes presenting in
diabetic ketoacidosis whilst taking them. It essential that acute medical
teams are vigilant for such presentations as the prevalence of SGLT2
inhibitor prescribing increases.
The other possible answers (metformin / gllmepiride / aspirin /

losartan) are not associated with the development of diabetic
ketoacidosis. It should, of course, be noted that metformin can lead to a
lactic acidosis.
Source: UK Government Drug Safety Bulletin (https://www.gov.uk/drug-

safety-update/ sglt2-inhibitors-updated-advice-on-the-risk-of-diabetic-
ketoacidos is)

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SGLT-2 inhibitors

(SGLT-2) in the renal proximal convoluted tubule to reduce glucose
reabsorption aind increase urinary glucose excretion.

• increased risk of lower-limb amputation: feet should be closely
monitored
Next question )
B I A .... c-:::>
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Q16
Which one of the following statements regarding dipeptidyl peptidase-4

inhibitors in the management of type 2 diabetes mellitus is correct?
Metformin should always be co-prescribed
Do not cause weight gain
Is given via a subcutaneous injection
An example is exenatide
Patients should be warned that hypoglycaemia is the most

common side-effect
Submit answer
Reference ranges v
Do not cause weight gain
Is given via a subcutaneous injection
An example is exenatide
Patients should be warned that hypoglycaemia is the most common

side-effect
Hypoglycaemia is rare in patients taking dipeptidyl peptidase-4

inhibitors.
,t •• • Discuss (1) Improve
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glucagon-like peptide-1 (GLP-1 ), a hormone released by the small




meal.
once a day.

NICE state the following :
Consider adding exenatide to metformin and a sulfonylurea if

comorbidities.

Dipeptidyl peptidase-4 (DPP-4) inhibitors ( e.g. Vildagliptin, sitagliptin)
Key points

Next question >
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Q17 [CJ
A 6-year-old South Sudanese boy is admitted progressive worsening of

his hearing loss. His mother is extremely concerned with his lack of
progress at school. Systems review reveals a 2-month history of
malaise, arthralgia and constipation. He has a past medical history of
deafness. On examination he has dry skin and thin hair; there were no
thyroid eye signs, no ophthalmoplegia and no myxoedema. He appears
to have a smooth symmetrically enlarged goitre, which is not painful.
Thyroid function tests:
Thyroid stimulating hormone 5.7 (mu/ I)
Free T4 9 pmol/1
Total T4 67 nmol/1
Which of the following causes of hypothyroidism is the patient suffering

from?
Iodine deficiency
Pendred syndrome
Thyroid agenesis
Atrophic hypothyroidism
Submit answer
Thyroid agenesis
Atrophic hypothyroidism
The patient is suffering from mild signs of hypothyroidism and

progressive bilateral deafness. Out of the following answers only
Pendred syndrome presents with signs of deafness and
hypothyroidism.
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Next question )
Pendred's syndrome
Pendred is an autosomal recessive genetic disorder that is

characterised by bilateral sensorineural deafness, with mild
hypothyroidism and a goitre. The patients tend to present with
progressive hearing loss and delay in academic progression. Often
head trauma tends to make the sensorineural deafness worse, leading
to patients having to avoid contact sports.
In Pendred syndrome there is a defect in the organification of iodine,

leading to dyshormonogenesis. However thyroid symptoms in pendred
syndrome are often mild and patients are often clinically euthyroid,
presenting only with a goitre. Thyroid function tests are also often
normal, requiring the perchlorate discharge test to aid diagnosis.
The syndrome can be diagnosed via genetic testing (Pendred syndrome

(PDS) gene, chromosome 7), audiometry and MRI imaging to look for
characteristic one and a half turns in the cochlea, compared to the
normal two and a half turns.
Treatment is with thvroid hormone replacement and cochlear implants.

Q18
A General Practitioner refers a 45-year-old fema le patient to the

endocrinology department with hypercalcaemia and raised parathyroid
hormone levels. Her blood tests are highly suggestive of primary
hyperparathyroidism. Her past medical history includes type 2 diabetes,
which is well controlled on metformin alone.
Which feature would be the strongest indication for referral of the

patient for consideration of parathyroid surgery?
Co-existing type 2 diabetes
Post menopausal patient
Persistent hypercalcaemia over 4 years
Vitamin D deficiency
Age of 45
Submit answer
Reference ranges v
Persistent hypercalcaemia over 4 years
Vitamin D deficiency
l Age of 45
NICE guidelines clearly stipulate the circumstances under which

parathyroidectomy should be considered in primary
hyperparathyroidism. These are listed below:
• Age under 50 years.

• Adjusted serum calcium concentration that is 0.25 mmol/L or
more above the upper end of the reference range.
• Estimated glomerular filtration rate (eGFR) less than 60
ml/ min/ 1.73 m2 although this threshold depends on other
factors, such as age.
• Renal stones or presence of nephrocalcinosis on ultrasound or CT.
• Presence of osteoporosis or osteoporotic fracture.
• Symptomatic disease
From the potential answers offered, the patient's age under 50 is the
only answer that meets the NICE criteria.
(Source: NICE guidelines, hyperparathyroidism -

http://cks. nice. org. u k/hyperca lcaem ia)
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adenoma

• 1 5%: hyperplasia
• 1%: carcinoma

• peptic ulceration/constipation/ pancreatitis
• bone pain/fracture
• renal stones
• depression
• hypertension
Associations
• hypertension
Investigations
• raised calcium, low phosphate
• PTH may be raised or (inappropriately, given the raised ca lcium)
normal
hyperparathyroidism
Treatment
damage
Q19
A 58-year-old man comes for review in the diabetes clinic. He was

diagnosed as having type 2 diabetes mellitus (T2DM) around 1 O years
ago and currently only takes gliclazide and atorvastatin. Three years
ago he was successfully treated for bladder cancer. A recent trial of
metformin was unsuccessful due to gastrointestinal side-effects. He
works as an accountant, is a non-smoker and his BMI is 31 kg/ m 2 • His
annual bloods show the following:
Na+ 138 mmol/I
K+ 4 .1 mmol/1
Urea 4.3 mmol/1
Creatinine 104 µmol/1
HbA1c 62 mmol/mol (7.8%)
What is the most appropriate next step in management?
Add pioglitazone
Add exenatide
Add acarbose
Add repaglinide
Add sitagliptin
Submit answer
Add sitagliptin
Pioglitazone is contraindicated by his history of bladder cancer and may

contribute to his obesity. A DPP-4 inhibitor such as sitagliptin is
therefore the best option.
Exenatide generally causes weight loss and is therefore useful in obese

diabetics but he does not meet the NICE body mass index criteria of 35
kg/m 2 •
16 •t tt Discuss (4) Improve
Next question >

• HbA 1c targets have changed. They are now dependent on what
frailty
4 oral antidiabetic agents

(7. 5%)
Dietary advice
• encourag1e high fibre, low glycaemic index sources of
carbohydrates
fatty acids
diabetes
HbA1c targets

motivation
• HbA 1 c should be checked every 3-6 months until stable, then 6
monthly
• in 2015 the guidelines changed so HbA 1 c targets are now
HbA1c
Lifestyle 48
mmol/mol
(6.5%)
mmol/mol
(6.5%)

(7.0%)
Practical examples
• a patient is newly diagnosed with HbA 1c and wants to try lifestyle
HbA 1c is 51 mmol/mol (6.8%). You increase his metformin from
Management of T2DM HbA1c target

mmol/mol (7.5%) (7.0%)
Drug treatment

can't
tMtrotmln not tolerate-a or Cl
• if the HbA 1c has risen to 58 mmol/mol (7.5%) then a second drug
should be added from the following list
• - sulfonylurea
• - gliptin
• - pioglitazone
• if despite this the HbA1 c rises to, or remains above 58 mmol/mol
should be offered:
• if despite this the HbA1c rises to, or remains above 58 mmol/mol
should be offered:
• - metformin + pioglitazone + SGLT-2 inhibitor
• - OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)

metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1 )
mimetic if:
• - BMI >= 35 kg/ m 2 and specific psychological or other medical
• - BMI < 35 kg/ m 2 and for whom insulin therapy would have

• only continue if there is a reduction of at least 11 mmol/mol
[1.0%] in HbA1c and a weight loss of at least 3% of initial body
weight in 6 months
Practical examples
metformin. Her HbA1c is 55 mmol/ mol (7.2%). You do not add
mmol/ mol (7.5%)
• a type 2 diabetic is found to have a HbA1c of 62 mmol/mol (7.8%)

• if the HbA1 c rises to 48 mmol/ mol (6.5%)* on lifestyle
interventions, consider one of the following :
• - sulfonylurea
• _. gliptin
• -+ pioglitazone
• if the HbA 1c has risen to 58 mmol/mol (7.5%) then a one of the
following combinations should be used:
• -+ gliptin + pioglitazone
• -+ gliptin + sulfonylurea
• _. pioglitazone + sulfonylurea
(7.5%) then consider insulin therapy
Starting insulin
• metformin should be continued. In terms of other drugs NICE
advice: 'Review the continued need for other blood glucose lowering
therapies'
• NICE recommend starting with human NPH insulin (isophane,
intermediate acting) taken at bed-time or twice daily according to
need
Blood pressure
• target is < 140/ 80 mm Hg (or < 130/ 80 mm Hg if end-organ
damage is present)
Antiplatelets
• should not be offered unless a patient has existing cardiovascular
disease
Lipids
• following the 2014 NICE lipid modification guidelines only patients
with a 10-year cardiovascular risk > 10% (using QRISK2) should be
offered a statln. The first-line statin of choice is atorvastatin 20mg
on
Pnmary pnr,enuon &teond.lry ~ventton

10.yu. Ca'dio'laltlDf ~ n 10'!<. CA 1thH1rt0HN,tOR
moat type 1 clalletlcs OR IC!Mr . . . . OR
CKDIIGf'R 1011~ -..twall . . . . . . . . . .
- - - - -•- - - - - - - - -•- - - - -
Atorva5taun 20mg od
AtotVastat n IOmg oa
noM-iDL tl • noc fMn DY u .& 1tltn
CCl'l.lid9f lmlli!lg ~ to 80n,g
*this is a bit confusing because isn't the diagnostic criteria for T2DM
HbA1c 48 mmol/ mol (6.5%)? So shouldn't all patients be offered
again metformin should be offered
Next question )
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Q20
Each one of the following is associated with

pseudohypoparathyroidism, except:
Low calcium levels
Low PTH levels
Shortened 4th and 5th metacarpals
Low IQ
Short stature
Submit answer
Reference ranges v
I Low PTH levels
Shortened 4th and 5th metacarpals
Low IQ
Short stature
Next question )
Hypoparathyroidism
Primary hypoparathyroidism
• decrease PTH secretion
• e.g. secondary to thyroid surgery*
• low calcium, high phosphate
• treated with alfacalcidol
The main symptoms of hypoparathyroidism are secondary to

hypocalcaemia:
• tetany: muscle twitching, cramping and spasm
• perioral paraesthesia
• Trousseau's sign: carpal spasm if the brachia I artery occluded by
inflating the blood pressure cuff and maintaining pressure above
systolic
• Chvostek's sign: tapping over parotid causes facial muscles to
twitch
• if chronic: depression, cataracts
• ECG: prolonged QT interval
• target cells being insensitive to PTH
• due to abnormality in a G protein
• associated with low IQ, short stature, shortened 4th and 5th
metacarpals
• low calcium, high phosphate, high PTH
• diagnosis is made by measuring urinary cAMP and phosphate
levels following an infusion of PTH. In hypoparathyroidism this
will cause an increase in both cAMP and phosphate levels. In
pseudohypoparathyroidism type I neither cAMP nor phosphate
levels are increased whilst in pseudohypoparathyroidism type II
only cAMP rises.
Pseudopseudohypoparathyroidism
• similar phenotype to pseudohypoparathyroidism but normal
biochemistry
*this may seem an oxymoron, but most medical textbooks classify

hypoparathyroidism which is secondary to surgery as being 'primary
hypoparathyroidism'
Next question )
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Search textbook ...

-
Q21
A 68-year-old woman is found to have the following blood tests:
TSH 0.05 mu/ I
Free T4 19 pmol/ 1(range 9-25 pmol/1)
Free T3 7 pmol/1 (range 3-9 pmol/1)
If left untreated, what are the most likely possible consequences?
Supraventricular arrhythmias and osteoporosis
Supraventricular arrhythmias and hyperlipidaemia
Hypothyroidism and impaired glucose tolerance
Myasthenia gravis and hypothyroidism
Impaired glucose tolerance and hyperlipidaemia
Submit answer
Reference ranges v
Q21
A 68-year-old woman is found to have the following blood tests:
TSH 0.05 mu/ I
Free T4 19 pmol/I (range 9-25 pmol/ 1)
Free T3 7 pmol/1 (range 3-9 pmol/ I)
If left untreated, what are the most likely possible consequences?
I Supraventricular arrhythmias and osteoporosis
Supraventricular arrhythmias and hyperlipidaemia
Hypothyroidism and impaired glucose tolerance
Myasthenia gravis and hypothyroidism
Impaired glucose tolerance and hyperlipidaemia
,. ,. • Discuss (2) Improve ]
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Next question )
Subclinical hyperthyroidism
Subclinical hyperthyroidism is an entity which is gaining increasing

recognition. It is defined as:
• normal serum free thyroxine and triiodothyronine levels
• with a thyroid stimulating hormone (TSH) below normal range
(usually< 0.1 mu/I)
Causes
• multinodular goitre, particularly in elderly females
• excessive thyroxine may give a similar biochemical picture
The importance in recognising subclinical hyperthyroidism lies in the

potential effect on the cardiovascular system (atrial fibrillation) and
bone metabolism (osteoporosis). It may also impact on quality of life
and increase the likelihood of dementia
Management
• TSH levels often revert to normal - therefore levels must be
persistently low to warrant intervention
• a reasonable treatment option is a therapeutic trial of low-dose
antithyroid agents for approximately 6 months in an effort to
induce a remission
Next question )
B I A ... ·-
·- 2,-: -- . . . T I""
Q22
A 45-year-old woman who has a history of Graves' disease presents

with visual problems. She is known to have Graves' ophthalmopathy
and does not currently smoke. Her most recent thyroid function tests
are shown below:
Free T4 15 pmol/1
TSH 1.6 mu/I
Which one of the following features is the strongest indicator of the

need for urgent ophthalmology review?
Sensitivity of eyes to light
Diplopia
Troublesome eyelid retraction
Awareness of change in intensity or quality of colour vision
Erythema of the conjunctiva
Submit answer
Awareness of change in intensity or quality of colour vision
Erythema of the conjunctiva
The other symptoms/signs indicate the need for non-urgent review by

an opthalmologist. Please see the EUGOGO guidelines for more details.
" 'f - Discuss (2) Improve ]
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Thyroid eye disease

disease.
Pathophysiology
inflammation
Prevention
disease. Prednisolone may help reduce the risk

Features
presentation
• exophthalmos
• ophthalmoplegia
Management
• steroids
• radiotherapy
• surgery

or both eyes
• disc swelling
Next question )
BI !!f A~
Q23
A 53-year-old man with a history of type 2 diabetes mellitus is reviewed

in the diabetes clinic. Twelve months ago his HbA1 c was 9 .7% despite
maximal oral hypoglycaemic therapy. Insulin was started and his most
recent HbA1c is 8.2%. He is considering applying for a HGV licence and
asks for advice. What is the most appropriate advice?
He cannot drive a heavy goods vehicle if he is taking insulin
He may be able to apply for a HGV licence if he meets strict

criteria relating to hypoglycaemia
He should stop insulin and start meglitinide
As under 55 years of age there is no requirement to inform the

DVLA
He needs to have been stable on insulin for at least 5 years

before applying
Submit answer
Reference ranges v
He may be able to apply for a HGV licence if he meets strict criteria
relating to hypoglycaemia
He should stop insulin and start meglitinide
As under 55 years of age there is no requirement to inform the DVLA
He needs to have been stable on insulin for at least 5 years before

applying
Patients on insulin may now hold a HGV licence if they meet strict
DVLA criteria
Importance: 50
116 11
Next question )
DVLA: diabetes mellitus
Until recently people with diabetes who used insulin could not hold a
HGV licence. The DVLA changed the rules in October 2011. The
following standards need to be met (and also apply to patients using
other hypoglycaemic inducing drugs such as sulfonylureas):
• there has not been any severe hypoglycaemic event in the
previous 12 months
• the driver has full hypoglycaemic awareness
• the driver must show adequate control of the condition by regular
blood glucose monitoring*, at least twice daily and at times
relevant to driving
• the driver must demonstrate an understanding of the risks of
hypoglycaemia
• here are no other debarring complications of diabetes
From a practical point of view patients on insulin who want to apply for
a Group 2 (HGV) licence need to complete a VDIAB1 I form.
Other specific points for group 1 drivers:

• if on insulin then patient can drive a car as long as they have
hypoglycaemic awareness, not more than one episode of
hypoglycaemia requiring the assistance of another person within
the preceding 12 months and no relevant visual impairment.
Drivers are normally contacted by DVLA
• if on tablets or exenatide no need to notify DVLA. If tablets may
induce hypoglycaemia (e.g. sulfonylureas) then there must not
have been more than one episode of hypoglycaemia requiring the
assistance of another person within the preceding 12 months
• if diet controlled alone then no requirement to inform DVLA
*to demonstrate adequate control, the Secretary of State's Honorary

Medical Advisory Panel on Diabetes Mellitus has recommended that
applicants will need to have used blood glucose meters with a memory
function to measure and record blood glucose levels for at least 3
months prior to submitting their application
Next question )
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Q24
Which one of the following types of oral steroid has the least amount of
mineralocorticoid activity?
Fludrocortisone
Hydrocortisone
Dexamethasone
Prednisolone
Cortisone
Submit answer
Reference ranges v
Dexamethasone
Prednisolone
Cortisone
This is clinically relevant as there are some situations where it is

important to combine high glucocorticoid (anti-inflammatory) activity
with minimal mineralocorticoid (fluid-retention) effects. A good
example is the use of dexamethsone for patients with raised
intracranial pressure secondary to brain tumours .
116 11
f • Discuss Improve
Next question )
Corticosteroids
Corticosteroids are amongst the most commonly prescribed therapies

in clinical practice. They are used both systemically (oral or
intravenous) or locally (skin creams, inhalers, eye drops, intra-articular).
They augment and in some cases replace the natural glucocorticoid
and mineralocorticoid activity of endogenous steroids.
The relative glucocorticoid and mineralocorticoid activity of commonly

used steroids is shown below:
The relative glucocorticoid and mineralocorticoid activity of commonly used steroids is shown
below:
Minimal Predominant Very high

glucocorticoid Glucocorticoid glucocorticoid glucocorticoid
activity, very high activity, high activity, low activity, minimal
mineralocorticoid mineralocorticoid mineralocorticoid mineralocorticoid
activity, activity, activity activity
Fludrocortisone Hydrocortisone Prednisolone Dexamethasone

Betmethasone
Side-effects
The side-effects of corticosteroids are numerous and represent the single greatest limitation on
their usage. Side-effects are more common with systemic and prolonged therapy.
• endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism,
hyperlipidaemia
Cam Scanner -, I.&~ a.:..~ I

• endocrine: impaired glucose regulation, increased appetite/weight
• neutrophilia
• fluid retention
• hypertension
Selected points on the use of corticosteroids:

• patients on long-term steroids should have their doses doubled
during intercurrent illness
• the BNF suggests gradual withdrawal of systemic corticosteroids
if patients have: received more than 40mg prednisolone daily for
more than one week, received more than 3 weeks treatment or
recently received repeated courses
Next question )
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.t. l ,..
== 1-
i:
=..,.
Save my notes
Q25
A 45-year-old man with a history of depression and gastro-oesophageal

reflux disease presents due to a milky discharge from his nipples. The
following blood results are obtained :
Prolactin 700 mu/ I
Which one of his medications is most likely to be responsible?
Omeprazole
Fluoxetine
Metoclopramide
Cimetidine
Amitriptyline
Submit answer
Reference ranges v
Fluoxetine
Metoclopramide
Cimetidine
Amitriptyline
Causes of raised prolactin - the p's

• pregnancy
• prolactinoma
• physiological
• primary hypothyroidism
• phenothiazines, metoclopramide, domperidone
Importance: 50
Selective serotonin reuptake inhibitors such as fluoxetine have rarely

been associated with hyperprolactinaemia but the most likely cause in
this patient is metoclopramide. Cimetidine is generally associated with
gynaecomastia, rather than galactorrhoea.
"' If • Discuss (3) Improve
Next question )
Next question )
Prolactin is secreted by the anterior pituitary gland w ith release being

controlled by a wide variety of physiological factors . Dopamine acts as
the primary prolactin releasing inhibitory factor and hence dopamine
agonists such as bromocriptine may be used to control galactorrhoea.
Features of excess prolactin

• men: impotence, loss of libido, galactorrhoea
• women: amenorrhoea, galactorrhoea
Causes of raised prolactin

• prolactinoma
• pregnancy
• oestrogens
• acromegaly: 1/3 of patients
• primary hypothyroidism (due to thyrotrophin releasing hormone
(TRH) stimulating prolactin release)
Drug causes of raised prolactin

• metoclopramide, domperidone
• phenothiazines
• haloperidol
• very rare: SSRls, opioids
Next question )
B / ~ A "" := ~= ="" T I"" !ffl "" ~ c-:,

Q26 [Cl
A 54-year-old woman who has had a hysterectomy presents for advice

about hormone replacement therapy. Which one of the follow ing would
result from the use of a combined oestrogen-progest ogen preparat ion
compared to an oestrogen-only preparation?
Decreased risk of venous thromboembolism
Increased risk of a stroke
Increased risk of breast cancer
Increased risk of endometrial cancer
Better control of symptoms
Submit answer
Reference ranges v
Increased risk of a stroke
Better control of symptoms
HRT: adding a progestogen increases the risk of breast cancer

Importance: 50
This is the rationale behind giving women who've had a hysterectomy

oestrogen-only treatment. The BNF states that the stroke risk is the
same regardless of whether the HRT preparation contains
progesterone.
116 •t • Discuss (2) Improve
Next question )
Hormone replacement therapy: adverse effects
Hormone replacement therapy {HRT) involves the use of a small dose

of oestrogen (combined with a progestogen in women with a uterus) to
help alleviate menopausal symptoms.
Side-effects
• nausea
• breasttenderness
• fluid retention and weight gain
Potential complications
• increased risk of breast cancer: increased by the addition of a
progestogen
• increased risk of endometrial cancer: reduced by the addition of a
progestogen but not eliminated completely. The BNF states that
the additional risk is eliminated if a progestogen is given
continuously
• increased risk of venous thromboembolism: increased by the
addition of a progestogen
• increased risk of stroke
• increased risk of ischaemic heart disease if taken more than 1 O
years after menopause
Breast cancer
• In the Women's Health Initiative (WH I) study there was a relative
risk of 1.26 at 5 years of developing breast cancer
• the increased risk relates to duration of use
• breast cancer incidence is higher in women using combined
preparations compared to oestrogen-only preparations
• the risk of breast cancer begins to decline when HRT is stopped
and by 5 years it reaches the same level as in women who have
never taken H RT
Next question )
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Q27
A 52-year-old woman who was diagnosed as having primary atrophic

hypothyroidism 12 months ago is reviewed following recent thyroid
function tests (TFTs):
TSH 12.5 mU/ 1
Free T4 14 pmol/ 1
She is currently taking 75mcg of levothyroxine once a day. How should

these results be interpreted?
Poor compl iance with medication
Her thyroxine dose needs to be increased
Evidence of recent systemic steroid therapy
She is on the correct dose
T 4 to T3 conversion disorder
Submit answer
Reference ranges v
A 52-year-old woman who was diagnosed as having primary atrophic
hypothyroidism 12 months ago is reviewed following recent thyroid
function tests (TFTs):
TSH 1 2. 5 mU/ 1
Free T4 14 pmol/1
She is currently taking 75mcg of levothyroxine once a day. How should

these results be interpreted?
I Poor compliance with medication
Her thyroxine dose needs to be increased
Evidence of recent systemic steroid therapy
She is on the correct dose
T 4 to T3 conversion disorder
The TSH level is high. This implies that over recent days/ weeks her
body is thyroxine deficient. However, her free T 4 is within normal range.
The most likely explanation is that she started taking the thyroxine
properly just before the blood test. This would correct the thyroxine
level but the TSH takes longer to norma lise.
16 11, tl Discuss (5) Improve
Next question )
The interpretation of thyroid function tests is usually straightforward:
Free
Diagnosis TSH T4 Notes
Thyrotoxicosis (e.g. Low High In T3

Graves' disease) thyrotoxicosis
the free T 4 will
be normal
Primary hypothyroidism High Low

(primary atrophic
hypothyroidism)
Secondary hypothyroidism Low Low Replacement

steroid therapy
is required prior
to thyroxine
Sick euthyroid syndrome* Low** Low Common in

hospital
inpatients
T3 is particularly
low in these
patients
Subclinical hypothyroidism High Normal
Poor compliance with High Normal

thyroxine
Steroid therapy Low Normal

Hypothyroid ism Hyperthyrodfsm
H s.h1moto's
Rt
--
th~ro;dr IS
ri lhyrotd1US
Subacule lh~ ro1d I.is
(de Ou rv n's)
Amx>darone
Graves' a,s as.e
Toxic mu I nodular gc)llre

Postpartum thyroktrtis
lodme defic1 nc ,.,...~tt.- -
Lllhlum

*now referred to as non-thyroidal illness

**TSH may be normal in some cases
Next question )
B / l!J
Save my notes
Q28
A 20-year-old man presents with a nine month history of weight gain.

Prior to this he was of a normal weight and cannot identify any obvious
lifestyle changes that would account for his obesity. On examination he
is noted to have abdominal striae and a degree of proximal myopathy.
Blood pressure is 130/80 mmHg. Bloods show the following:
Na+ 141 mmol/1
K+ 3.3 mmol/1
Bicarbonate 26 mmol/1
Urea 3.3 mmol/1
What is the most appropriate next test?
High-dose dexamethasone suppression test
Plasma ACTH
Short ACTH test
24 hour urinary free cortisol
Renin:aldosterone ratio
Submit answer
Reference ranges v
Plasma ACTH
Short ACTH test
24 hour urinary free cortisol
The overnight dexamethasone suppression test is the best test to

diagnosis Cushing's syndrome
Importance: 50
There is some debate as to whether a 24 hour urinary free cortisol or an

overnight dexamethasone suppression test should be used to screen
patients for Cushing's. The overnight (not high-dose) dexamethasone
suppression test has however been shown to be more sensitive and is
now much more commonly used in clinical practice. As this is not
offered then 24 hour urinary free cortisol is the next best answer
For a review comparing diagnostic methods see 'Specificity of first-line

tests for the diagnosis of Cushing's syndrome: assessment in a large
series, J Clin Endocrinol Metab. 2007 Nov;92(11 ):4123-9'
The high-dose dexamethasone suppression test is used to help

differentiate the cause of Cushing's syndrome
[ ,6 ,. - Discuss (9) Improve ]
Next question )
Q29
A 44-year-old woman presents to her GP as she is feeling 'hot an the

t ime' and is consequently worried she is going through an early
menopause. Her husband has also noticed a 'fullness' of her neck
which has become apparent over the past few weeks. On examination
her pulse is 90/minute and she has a small, non-tender goitre. Blood
tests are arranged:
TSH < 0.05 mu/I
Free T4 24 pmol/I
Anti-thyroid peroxidase antibodies 102 IU/ml (< 35 IU/ml)
ESR 23 mm/hr
Thyroid cancer
Graves' disease
I
Submit answer
Q29
A 44-year-old woman presents to her GP as she is feeling 'hot all the

time' and is consequently worried she is going through an early
menopause. Her husband has also noticed a 'fullness' of her neck
which has become apparent over the past few weeks. On examination
her pulse is 90/minute and she has a small, non-tender goitre. Blood
tests are arranged:
TSH < 0.05 mu/ I
Free T4 24 pmol/1
Anti-thyroid peroxidase antibodies 102 IU/ ml (< 35 IU/ml )
ESR 23 mm/ hr
Thyroid cancer
Graves' disease
Submit answer
Reference ranges v
Thyroid cancer
Graves' disease
The thyrotoxic symptoms and blood tests, goitre and anti-thyroid

peroxidase antibodies suggest a diagnosis of Graves' disease.
Whilst anti-thyroid peroxidase antibodies are seen in 90% of

Hashimoto's disease they are also seen in 75% of patients with Graves'
disease. Hashimoto's thyroiditis is also generally associated with
hypothyroidism, which is not in keeping with this presentation.
The ESR result is within normal range.
11• at • Discuss (6) Improve
Next question )
Next question )

Features
• typica l features of thyrotoxicosis

• eye signs (30% of patients)
o exophthalmos
o ophthalmoplegia
o digital clubbing
Autoantibodies
• TSH receptor stimulating antibodies (90%)
Next question )
B / f!!j
Q30 Jc:::1
Which one of the following is most likely to be found in a patient with

Hashimoto's thyroiditis?
Raised ESR
Anti-TSH receptor stimulating antibodies
Anti-thyroid peroxidase antibodies
Decreased TSH
Co-existing type 2 diabetes mellitus
Submit answer
Reference ranges v
Anti-TSH receptor stimulating antibodies
Anti-thyroid peroxidase antibodies
Decreased TSH
Co-existing type 2 diabetes mellitus
Hashimoto's thyroiditis =hypothyroidism+ goitre+ anti-TPO

Importance: 50
"' .. t9 Discuss (1) Improve ]
Next question )

Next question )
Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is an

autoimmune disorder of the thyroid gland. It is typically associated with
hypothyroidism although there may be a transient thyrotoxicosis in the
acute phase. It is 1 Otimes more common in women
Features
• features of hypothyroidism
• goitre: firm, non-tender
• anti-thyroid peroxidase and also anti-Tg antibodies
Hashrmoto's
thyroidius &lbacute thyroid tis
(da Querva:n's) Graves· disease
0.
Anuodarone lox1c mu t nodular goitre

Riedel's thyroid1 s
Postpartum thyrotd,tis
..

Next question )
Q1
You review a 68-year-old man who has chron ic obst ructive pulmonary
disease (COPD). Each year he typically has around 7-8 courses of ora l
prednisolone to treat infective exacerbations of his COPD. Which one of
the following adverse effects is linked to long-term steroid use?
Osteomalacia
Enophthalmos
Leucopaenia
Avascular necrosis
Constipation
Submit answer
Reference ranges v
Enophthalmos
Leucopaenia
Avascular necrosis
Constipation
Long-term corticosteroid use is linked to osteopaenia and osteoporosis,

rather than osteomalacia.
[ "' If • Discuss Improve ]
Next question )
r,. - _ ... : - - - .a. - - - : J -
Q2
A 75-year-old woman with a history of hypothyoidism is admitted to the

Emergency Department following an episode of chest pain. She is
diagnosed as having an acute coronary syndrome and iron-deficiency
anaemia. A percutaneous coronary intervention is performed and a
coronary artery stent is inserted. Endoscopies of the upper and lower
gastrointestinal tract are performed and reported as normal. She is
discharged on the following drugs in addition to her regular
levothyroxine: aspirin, clopidogrel, ramipril, lansoprazole, simvastatin
and ferrous sulphate. Six weeks later she complains of feeling tired all
the time. Her GP arranges some routine blood tests:
Hb 11 .9 g/ dl
Platelets 1 55 * 1o9/ I
WBC 5.2 * 109 / 1
Free T 4 8.1 pmol/ 1
TSH 8.2 mu/ I
Prior to her recent admission the TSH has been within range for the
past two years. Which one of the following new drugs most likely
explains the raised TSH?
Simvastatin
Clopidogrel
Ferrous sulphate
Ramipril
Lansoprazole
Clopidogrel
Ferrous sulphate
Ramipril
Lansoprazole
Iron reduces the absorption of thyroxine

Importance: 50
[ ,t •t • Discuss (3) Improve ]
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I I _ __ _ _ _._ 1 _ _ • I•
Key points
TSH in this range

Interactions
apart
Q3 fc::J
A 42-year-old man presents to the emergency department complaining

of long-standing muscle weakness and headaches. His blood pressure
is 176/78 mmHg, but all other observations are within normal limits.
Examination is unremarkable.
Blood results are as follows:
Na+ 145 mmol/L (135 - 145)
K+ 2.8 mmol/L (3.5- 5.0)
Bicarbonate 34 mmol/L (22 - 29)
Urea 4 mmol/L (2.0 - 7.0)
Creatinine 72 µmol/L (55 - 120)
What is the most appropriate first-li ne investigation?
Adrenal vein sampling
CTabdomen
Dexamethasone suppression test
Plasma aldosterone/ renin ratio
Submit answer
Reference ranges v
CTabdomen
Dexamethasone suppression test
Plasma aldosterone/ renin ratio
A plasma aldosterone/renin ratio is the first-line investigation in

suspected primary hyperaldosteronism
Importance: 50
Features of hypokalaemia coupled with hypertension are suggestive of

primary hyperaldosteronism. This can be caused by an adrenal
adenoma (Conn's syndrome) or bilateral idiopathic adrenal hyperplasia.
The first line investigation for this is a plasma aldosterone/renin ratio,
which should show high aldosterone levels alongside low renin levels.
Adrenal vein sampling and CT abdomen can be useful in differentiating

between the different causes of primary hyperaldosteronism, but would
not be appropriate first-line investigations.
The short synacthen test is the first-line investigation for adrenal

insufficiency. This would typically present with hyponatraemia and
hypotension.
Dexamethasone suppression tests are useful in the investigation

adrenal gland function and is typically used to investigate for Cushing's
disease.
a6 f
Next question )

Features
• hypertension
• hypokalaemia
• alkalosis
Investigations
aldosterone)
Management
spironolactone
Q4
Which one of the following increases the risk of developing peripheral

oedema in a patient taking pioglitazone?
Concomitant use with gliclazide
Serum sodium < 140 mmol/1
Concomitant use with insulin
Concomi1ant use with metformin
Serum potassium< 4.0 mmol/1
Submit answer
Reference ranges v
I Concomitant use with insulin
Concomitant use with metformin
Serum potassium < 4.0 mmol/1
•• •• • Discuss (5) Improve
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Thiazolidinediones
Thiazol idinediones are a class of agents used in the treatment of type 2

diabetes mellitus. They are agonists to the PPAR-gamma receptor and
reduce peripheral insulin resistance. Rosiglitazone was withdrawn in
201 0 following concerns about the cardiovascular side-effect profile.

natural ligands are free fatty acids and it is t hought to control adipocyte
differentiation and function.
Adverse effects
• weight gain
• fluid retention - therefore contraindicated in heart failu re. The risk
• recent studies have indicated an increased risk of fractures
bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
Next question )
QS
A 67-year-old man who has a history of type 2 diabetes mellitus and

benign prostatic hypertrophy presents with burning pain in his feet. This
has been present for the past few months and is getting gradually
worse. He has tried taking duloxetine but unfortunately has received no
benefit. Clinical examination is unremarkable other than diminished
sensation to fine touch on both soles. What is the most suitable initial
management?
Carbamazepine
Amitriptyline
Pregabalin
Fluoxetine
Sodium valproate
Submit answer
Reference ranges v
Pregabalin
Fluoxetine
Sodium valproate
Amitriptyllne would normally be first choice but given his history of

benign prostatic hyperplasia it is better to avoid amitriptyline due to the
risk of urinary retention.
•• •• • Discuss (1) Improve
Next question )
Diabetic neuropathy
cliniical practice.

pregabalin
drugs
neuropathic pain
problems
Gastroparesis
vomiting
Chronic diarrhoea

Next question )
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Q6
A 45-year-old man is investigated following referra l to the endocrinology

clinic with polydipsia. Plasma glucose and calcium are normal. A water
deprivation test is performed with the following results:
Starting plasma osm. 319 mOsmol/ 1(275-295 mOsmol/ 1)
Final urine osm. 142 mOsmol/1
Urine osm. post-DOAVP 885 mOsmol/ 1
Psychogenic polydipsia
Nephrogenic diabetes insipidus
Cranial diabetes insipidus
Submit answer
Reference ranges v
I Cranial diabetes insipid_u_s _ _ _ _ ~
A dramatic improvement is seen in the ability of the kidneys to
concentrate urine following the administration of DDAVP. This points
towards a diagnosis of cranial diabetes insipidus
"' •• tt Discuss (3) Improve
Next question )
Water deprivation test
Method
• prevent patient drinking water
• ask patient to empty bladder
• hourly urine and plasma osmolalities
Final
Starting urme Urine osm.
plasma osm. osm. post-DDAVP
Normal Normal > 600 > 600
Psychogenic Low > 400 > 400

polydipsia
Cranial DI High < 300 > 600
Nephrogenic DI High < 300 < 300
Next question )
Q7
An 24-year-old woman is reviewed due to facial hirsutism. You suspect

a diagnosis of polycystic ovarian syndrome (PCOS). Which one of the
following features would suggest the need for further investigations
before confidently making a diagnosis of PCOS?
Clitoromegaly
Acanthosis nigricans
Obesity
Amenorrhoea
Acne
Submit answer
Reference ranges v
Q7
An 24-year-old woman is reviewed due to facial hirsutism. You suspect

a diagnosis of polycystic ovarian syndrome (PCOS). Which one of the
following features would suggest the need for further investigations
before confidently making a diagnosis of PCOS?
I Clitoromegaly
---------
Acanthosis nigricans
Obesity
Amenorrhoea
Acne
Clitoromegaly is seen occasionally in PCOS but is normally associated

with very high androgen levels. If clitoromegaly is found then further
investigations to exclude an ovarian or adrenal androgen secreting
tumour are required.
[ ,, .. t9 Discuss (2) Improve ]

• f
1 • Discuss (2) Improve
Next question )
Polycystic ovarian syndrome: features and

investigation
Polycystic ovary syndrome (PCOS) is a complex condition of ovarian

dysfunction thought to affect between 5-20% of women of reproductive
age. The aetiology of PCOS is not fully understood. Both
hyperinsulinaemia and high levels of luteinizing hormone are seen in
PCOS and there appears to be some overlap with the metabolic
syndrome.
Features
• subfertility and infertility
• menstrual disturbances: oligomenorrhea and amenorrhoea
• hirsutism, acne (due to hyperandrogenism)
• obesity
• acanthosis nigricans (due to insulin resistance)
Investigations
• pelvic ultrasound: multiple cysts on the ovaries
• FSH, LH, prolactin, TSH, and testosterone are useful
investigations: raised LH:FSH ratio is a 'classical' feature but is no
longer thought to be useful in diagnosis. Prolactin may be normal
or mildly elevated. Testosterone may be normal or mildly elevated
- however, if markedly raised consider other causes
• check for impaired glucose tolerance
Next question )
'
QB
A 66-year-old man attends clinic for review of his diabetic control. He

has a history of type 2 diabetes mellitus, and was commenced on
metformin six months' ago. The patient's HbA1c today is 60mmol/ mol.
You discuss the patient with your consultant, who recommends
addition of empagliflozin for glycaemic control.
What is the mechanism of action of this medication?
Biguanide
Sulfonylurea
GLP-1 mimetic
SGLT-2 inhibitor
DPP-4 inhibitor
Submit answer
Reference ranges v
SGLT-2 inhibitor
DPP-4 inhibitor
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter

2 (SGLT-2) in the renal proximal convoluted tubule
Importance: 50

(SGLT-2) in the renal proximal convoluted tubule. In doing so, they
reduce glucose reabsorption and increase urinary glucose excretion.
This mechanism explains their main side effects - increased urine
output, weight loss and urinary infections. Examples include
canagliflozin, dapagliflozin and empagliflozin.
SGLT-2 inhibitors are often the best option in patients with ischaemic
heart disease and heart failure who have not achieved adequate
glycaemic control on metformin alone.
Important adverse effects include:

• Urinary and genital infection (secondary to glycosuria).
• Normoglycaemic ketoacidosis
• Increased risk of lower-limb amputation: feet should be closely
monitored
Biguanides (such as metformin) act to decrease gluconeogenesis in the

liver and increase insulin sensitivity.
Sulfonylureas (such as gliclazide) act to increase insulin release from

beta-cells in the pancreas.
GLP-1 mimetics (such as exenatide) mimic incretin which is usually

released in the gastrointestinal tract, and has the effect of increasing
insulin production.
DPP-4 inhibitors (such as sitagliptin) act to block the action of DPP-4,
an enzyme which breaks down incretin.
11• If tt Discuss Improve
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SGLT-2 inhibitors


monitored
Next question )
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Q9
A 29-year-female, who is 4 months post-partum, presents with a 3-week

history of weight loss, heat intolerance, tremor, palpitation and
diarrhoea. Pregnancy and birth were uncomplicated. On further
questioning, she admits having taken off-license weight loss
medication bought from the internet 1 month ago. Past medical history
and family history are insignificant. She does not smoke or drink
alcohol.
On physical examination, she has exophthalmos, brisk reflexes and fine

tremor. Her vital signs were heart rate 98/minute, blood pressure
136/76 mmHg, temperature 36.5°C. The thyroid gland was diffusely
enlarged.
Thyroid Stimulating Hormone (TSH) 0.02 mU/1
Free thyroxine (T4) 24 pmol/1
Total thyroxine (T4) 1 SO nmol/1
Exogenous thyroxine
Graves' Disease
Post-partum thyroiditis
Submit answer
I Graves' Disease
Post-partum thyroiditis
Graves' disease may present first or become worse during the

post-natal period
Importance: 50
This is a case of hyperthyroidism due to Graves' disease. Graves'

disease may manifest itself or worsen during pregnancy and the post-
natal period.
Exophthalmos is a specific sign seen in Graves' disease and not in other

hyperthyroid conditions.
Hashimoto's thyroiditis leads to hypothyroidism.
In post-partum thyroiditis, the woman initially develops hyperthyroidism

immediately after birth followed by normal or sometimes decreased
thyroid levels.
De Quervain's thyroiditis can present with pain and dysphagia and may
lead to high, normal or low thyroid levels.
[ ,. •• • Discuss (4) Improve ]
Next question )
l 'f CJ\l \.{ UC.:>l l UI I r

Thyrotoxicosis
Untreated thyrotoxicosis increases the risk of feta! loss, maternal heart


Management
choice
following: 'Propylthiouracil is used in the first trimester of pregnancy
in place of carbimazo/e, as the latter drug may be associated with
carbimazole'
• maternal free thyroxine level s should be kept in the upper third of
thyroid problems
Hypothyroid ism
Key points
pregnancy
Next question )
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Q10
A 72-year-old male is seen in clinic complaining of pain in both feet. He

reports the pain is burning in nature and worse at night when sitting
watching TV. It can often be severe and he is struggling to manage this
with paracetamol alone. He has a past medical history of poorly
controlled diabetes, hypertension and high cholesterol. On examination,
he has normal power bilaterally but reduced sensation. Pedal pulses are
present and there are no vascular related skin changes.
What is the most appropriate first line treatment for his pain?
Tramadol
Topical capsaicin
Codeine
Duloxetine
Naproxen
Submit answer
Reference ranges v
Topical capsaicin
Codeine
Duloxetine
Naproxen
First line treatment in diabetic neuropathy is with amitriptyline,

duloxetine, gabapentin or pregabalin
Importance: 50
The correct answer is duloxetine. This patient has a history of poorly

controlled diabetes and combined with the examination findings of
reduced sensation and normal pulses a diagnosis of diabetic
neuropathy is most likely. NICE guidelines suggest first-line treatment
for diabetic neuropathy is the same as for other causes of neuropathic
pain with amitriptyline, duloxetine, gabapentin or pregabalin.
Topical capsaicin can be used for localised neuropathic pain such as

postherpetic neuralgia but would not be first-line for this patient.
Tramadol is also not the first line treatment but can be used as rescue
therapy for exacerbations.
Neither codeine or naproxen are recommended in neuropathic pain.
a6 Rf t9 Discuss Improve
Next question >

Diabetic neuropathy
clinical practice.

pregabalin
drugs
neuropathic pain
problems
Gastroparesis
vomiting
Chronic diarrhoea

Q11
A 41-year-old woman presents with palpitations and heat intolerance.

On examination her pulse is 90/min and a small, diffuse goitre is noted
which is tender to touch. Thyroid function tests show the following :
Free T 4 24 pmoVI
TSH < 0.05 mu/ I
Grave's disease
Sick thyroid syndrome
Submit answer
Reference ranges v
Thyrotoxicosis with tender goitre= subacute (De Quervain's)

thyroiditis
Importance: 50
Whilst Grave's disease is the most common cause of thyrotoxicosis it

would not cause a tender goitre. In the context of thyrotoxicosis this
finding is only really seen in De Quervain's thyroiditis.
Hashimoto's thyroiditis is an autoimmune disorder of the thyroid gland.

It is typically associated with hypothyroidism although there may be a
transient thyrotoxicosis in the acute phase. The goitre is non-tender in
Hashimoto's.
116 •t - Discuss Improve
Next question >
Subacute (De Quervain's) thyroiditis

Subacute thyroiditis (also known as De Quervain's thyroiditis and
subacute granulomatous thyroiditis) is thought to occur following viral
infection and typically presents with hyperthyroidism.
There are typically 4 phases;

• phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised
ESR
• phase 2 (1-3 weeks) : euthyroid
• phase 3 (weeks - months): hypothyroidism
• phase 4: thyroid structure and function goes back to normal
Investigations
• thyroid scintigraphy: globally reduced uptake of iodine-131
Management
• usually self-limiting - most patients do not require treatment
• thyroid pain may respond to aspirin or other NSAIDs
• in more severe cases steroids are used, particularly if
hypothyroidism develops
Hypothyroidism .«yperthyrodlsm
H hlfflOto's
thyroid us
__
Subacute thyroid I.ls
(de Ouervam's) ..,
Anuodarone Tox c mull nodular 110«lre

R s 1hyroid1 tS
Postpartum lhynMditrs
lod~ de tciency ~ ··~·- · ..
L1th1Um

Q12
A 31-year-old female is under investigation for Addison's disease after

presenting with feeling tired all the time, weight loss and postural
hypotension. A 9 am cortisol result has returned at 150 nmol/1.
What is the most appropriate interpretation of this result?
Inconclusive result - should be repeated
Confirms a diagnosis of Addison's disease
Confirms a diagnosis of Conn's disease
Inconclusive result - should be referred for short Synacthen test
Excludes a diagnosis of Addison's disease
Submit answer
Reference ranges v
Confirms a diagnosis of Conn's disease
Inconclusive result - should be referred for short Synacthen test
Excludes a diagnosis of Addison's disease
9 am cortisol between 100-SOOnmol/l is inconclusive and requires

further investigation with a short synacthen test
Importance: 50
The correct answer is that this is an inconclusive result and the patient
should be further investigated with a short Synacthen test. 9 am
cortisol results between 100-500nmol/l are inconclusive and patients
should be referred to secondary care for further investigation. A result
less than 1 oonmol/I makes Addison's disease or hypoadrenalism likely,
whilst a result >S00nmol/1 makes a diagnosis of Addison's disease very
unlikely.
Simply repeating the test would not be the correct answer unless there
was concern that the test was not taken at the correct time.
A result of 150nmol/l would not confirm a diagnosis of Addison's

disease. A result <1 00nmol/I would suggest a definite abnormality but
the definitive investigation is a short Synacthen test.
A 9 am cortisol of 1 S0nmol/I would not confirm a diagnosis of Conn's

syndrome. Whilst 9 am cortisol can be useful in the diagnosis of Conn's,
patients typically require plasma renin:aldosterone level.
A 9 am cortisol above S00nmol/ I not below would make a diagnosis of

Addison's very unlikely.
16 .. • Discuss (2) Improve
Next question )
Next question )

is an ACTH stimulation test (short Synacthen test) . Plasma cortisol is
measured before and 30 minutes after giving Synacthen 250ug IM .
demonstrated.

• > 500 nmol/ I makes Addison's very unlikely
• < 100 nmol/ I is definitely abnormal
• 100-500 nmol/ I should prompt a ACTH stimu lation test to be
performed

• hyperkalaemia
• hyponatraemia
• hypoglycaemia
Next question )
B / ~ T I•
Q13
A 43-year-old man is admitted to hospital with pneumonia. His past

medical history includes Addison's disease for which he takes
hydrocortisone (20mg in the mornings and 10mg in the afternoon).
What is the most appropriate action with respect to his steroid dose?
Continue to take the same dose
Double hydrocortisone to 40mg mornings and 20mg afternoon
Halve hydrocortisone to 10mg mornings and 5mg afternoon
Continue to take the same dose + prescribe a proton pump

inhibitor
Continue the same morning dose + stop the afternoon dose
Submit answer
Reference ranges v
I Double hydrocortisone to 40mg mornings and 20mg afternoon
Halve hydrocortisone to 10mg mornings and 5mg afternoon
Continue to take the same dose + prescribe a proton pump inhibitor
Continue the same morning dose + stop the afternoon dose
Patients on long-term steroids should have their doses doubled

during intercurrent illness
Importance: 50
" •t • Discuss (4) Improve ]
Next question )
Q14
A 34-year-old female with a history of Addison's disease presents for

review in endocrinology clinic. She is generally well but complains of a
decrease in her libido. On examination there is a slight loss of pubic
hair. What is the most likely cause?
Adverse effect of hydrocortisone therapy
11-hydroxylase deficiency
Diethylstilbestrol deficiency
Oestrogen deficiency
Dehydroepiandrosterone (DHEA) deficiency
Submit answer
Reference ranges v
Diethylstilbestrol deficiency
Oestrogen deficiency
Dehydroepiandrosterone (DHEA) deficiency
Dehydroepiandrosterone is the most abundant circulating adrenal

steroid. Adrenal glands are the main source of dehydroepiandrosterone
in females - loss of functioning adrenal tissue as in Addison's disease
may result in symptoms secondary to androgen deficiency, such as loss
of libido. Research is ongoing as to whether routine replacement of
DHEA is beneficial
[ ,6 "f • Discuss (1) Improve ]
'
Next question )
1'4CJU ~UC~l l UI I r
Addison's disease
Autoimmune destruction of the adrenal glands is the commonest cause

of primary hypoadrenalism in the UK, accounting for 80% of cases. This
is termed Addison's disease and results in reduced cortisol and
aldosterone being produced.
Features
• lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-
craving'
• hyperpigmentation (especially palmar creases)*, vitiligo, loss of
pubic hair in women, hypotension, hypoglycaemia
• hyponatraemia and hyperkalaemia may be seen
• crisis: collapse, shock, pyrexia
Other causes of hypoadrenalism
Primary causes
• tuberculosis
• metastases (e.g. bronchial carcinoma)
• meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
• HIV
• antiphospholipid syndrome
Secondary causes
• pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
*Primary Addison's is associated with hyperpigmentation whereas

secondary adrenal insufficiency is not
Next question )
0 Q15
A 51-year-old woman is reviewed in the diabetes clinic. She was

diagnosed with type 2 diabetes mellitus 12 months ago and still has
poor glycaemic control (63 mmol/mol). She has recently had to stop
taking gliclazide due to repeated episodes of hypoglycaemia and is only
taking maximum dose metformin. Her BMI is 26 kg/mA2. What is the
most appropriate next step in management?
Add either pioglitazone, a DPP-4 inhibitor or a SGLT-2 inhibitor
Refer her for a laparoscopic gastric band
Refer her for insulin therapy
Add either a thiazolidinedione or exenatide
Add either a DPP-4 inhibitor or exenatide
Submit answer
Reference ranges v
Add either pioglitazone, a DPP-4 inhibitor or a SGLT-2 inhibitor
Refer her for a laparoscopic gastric band
Refer her for insulin therapy
Add either a thiazolldinedione or exenatide
Add either a DPP-4 inhibitor or exenatide
a6 •t tt Discuss (5) Improve
Next question )

• HbA1c targets have changed. They are now dependent on what
frailty

(7.5%)
Dietary advice
carbohydrates
fatty acids
diabetes
HbA1c targets
This is area which has changed in 201 5

motivation
• HbA 1c should be checked every 3-6 months until stable, then 6
monthly
• in 2015 the guidelines changed so HbA1 c targets are now
HbA1c
Lifestyle 48
mmol/mol
(6.5%)
mmol/mol
(6.5%)

(7.0%)
Practical examples
• a patient is newly diagnosed with HbA1 c and wants to try lifestyle
HbA 1c is 51 mmol/ mol (6.8%). You increase his metformin from
Management of T2DM HbA1c target

mmol/ mol (7. 5%) (7.0%)
Drug treatment

can't:
,..t1orm1n not tolerated or Cl
• if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug
• - sulfonylurea
• - gliptin
• - pioglitazone
• if despite this the HbA1c rises to, or remains above 58 mmol/ mol
should be offered:
• - metformin + pioglitazone + SGLT-2 inhibitor
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)

metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1)
mimetic if:
• - BMI >= 35 kg/ m 2 and specific psychological or other medical
• - BMI < 35 kg/ m 2 and for whom insulin therapy wou ld have

• only continue if there is a reduction of at least 11 mmol/mol
[1 .0%] in HbA1c and a weight loss of at least 3% of initial body
weight in 6 months
Practical examples
metformin. Her HbA1 c Is 55 mmol/ mol (7.2%). You do not add
mmol/mol (7.5%)
• a type 2 diabetic is found to have a HbA1c of 62 mmol/mol (7.8%)

• if the HbA1 c rises to 48 mmol/ mol (6.5%)* on lifestyle
interventions, consider one of the following:
• .... sulfonylurea
• .... gliptin
• .... pioglitazone
• if the HbA1 c has risen to 58 mmol/mol (7.5%) then a one of the
following combinations should be used:
• .... gliptin + pioglitazone
• .... gliptin + sulfonylurea
• -- pioglitazone + sulfonylurea
(7.5%) then consider insulin therapy
Starting insulin
• metformin should be continued. In terms of other drugs NICE
advice: 'Review the continued need for other blood glucose lowering
therapies'
• NICE recommend starting with human NPH insulin (isophane,
intermediate acting) taken at bed-time or twice daily according to
need
Blood pressure
• target is< 140/ 80 mmHg (or< 130/ 80 mmHg if end-organ
damage is present)
Antiplatelets
• should not be offered unless a patient has existing cardiovascular
disease
Lipids
• following the 2014 NICE lipid modification guidelines on ly patients
with a 10-year cardiovascular risk> 10% (using QRISK2) shou ld be
offered a statin. The first-line statin of choice is atorvastatin 20mg
on
Primary prevention Secondary prevention

10 yur CM:iiovntiar risk•• 10% OR nown IICMlffllC heawt OM-. OR
mott rp i clalletit1 OR ~ovnc-.._.OR
PII......,.,__,..._
CICDI~ ~
Atorva,tat111 20mg od
! non-HOL t1a1 not ~ by ,.,. , thin AtOfVHtat " IOmg od
c0f!Sidsr llhllllg up to 81lm;
"1his is a bit confusing because isn't the diagnostic criteria for T2DM
HbA 1c 48 mmol/ mol (6.5%)? So shouldn't all patients be offered
again metformin shou ld be offered
Next question )
B I !!J A .... ·-
·- 2=
1- -- 'IP'
01
Which one of the following features is least common ly seen in

Gitelman's syndrome?
Hypokalaemia
Hypertension
Metabolic alkalosis
Hypocalciuria
Hypomagnesaemia
Submit answer
Reference ranges v
Hypertension
Metabolic alkalosis
Hypocalciuria
Hypomagnesaemia
Gitelman's syndrome: normotension, hypokalaemia +

hypocalciuria
Importance: 50
9' f
11
• Discuss (3) Improve
Next question >
Gitelman's syndrome
Gitelman's syndrome is due to a defect in the thiazide-sensitive Na+ Cl-

transporter in the distal convoluted tubule.
Features
• normotension
• hypokalaemia
• hypocalciuria
• hypomagnesaemia
• metabolic alkalosis
Q2
Which one of the following is not part of the diagnostic criteria for the
metabolic syndrome?
High triglycerides
Low HDL
High LDL
Central obesity
Hypertension
Submit answer
Reference ranges v
LUVV nuL
High LDL
Central obesity
Hypertension
High LDL levels are not part of the World Health Organization or
International Diabetes Federation diagnostic criteria
[ ,6 •• tt Discuss Improve
Next question )
Metabolic syndrome
Unfortunately there are a number of competing definitions of the

metabolic syndrome around at the present time. It is thought that the
key pathophysiological factor is insulin resistance.
SIGN recommend using criteria similar to those from the American

Heart Association . The similarity of the International Diabetes
Federation criteria should be noted. For a diagnosis of metabolic
syndrome at least 3 of the following should be identified:
• elevated waist circumference: men > 102 cm, women > 88 cm
• elevated triglycerides: > 1.7 mmol/L
• reduced HDL: < 1.03 mmol/L in males and < 1.29 mmol/L in
females
• raised blood pressure: > 130/85 mmHg, or active treatment of
hypertension
• raised fasting plasma glucose > 5.6 mmol/L, or previously
diagnosed type 2 diabetes
s set of
The International Diabetes Federation produced a cons ensu
These require
diag nost ic criteria in 2005, whic h are now widely in use.
ence > 94cm
the presence of central obes ity (defined as wais t circu mfer
icity spec ific
for Europid men and > 80cm for Europid women, with ethn
facto rs:
values for othe r groups) plus any two of the follo wing four
tmen t for
• raised triglycerides level : > 1.7 mmo l/L, or spec ific trea
this lipid abnormality
< 1.29
• reduced HDL cholesterol: < 1.03 mm ol/L in male s and
rma lity
mmo l/L in females, or spec ific trea tmen t for this lipid abno
tmen t of
• raised blood pressure : > 130/ 85 mm Hg, or active trea
hypertension
ly
• raised fasti ng plas ma gluc ose> 5.6 mmo l/L, or previous
diagnosed type 2 diab etes
ic crite ria
In 1999 the World Health Organization produced diag nost
gluc ose
which required the presence of diabetes mellitus, impaired
AND two of
tolerance, impaired fasti ng gluc ose or insulin resistance,
the follo wing :
• blood pressure: > 140/ 90 mmH g
-den sity
• dyslipidaemia : trigly cerid es: > 1.695 mm ol/L and/ or high
mm ol/L
lipoprotein cholesterol (HDL-C) < 0.9 mm ol/L (male),< 1.0
(female)
ale),
• central obes ity: wais t:hip ratio > 0.90 (male), > 0.85 (fem
and/ or body mas s index > 30 kg/ m2
mg/ min or
• microalbuminuria: urinary albumin excretion ratio > 20
albumin:creatinine ratio > 30 mg/ g
Other associated features include:

• raised uric acid levels
• non-alco holic fatty liver disease
• polycystic ovarian synd rome
Nex t ques tion )

0 Q3
A 45-year-old woman presents with weight gain and recurrent 'dizzy'

episodes. Over the past four months she has gained 20 kg. The
episodes occur on an almost daily basis and are characterised by
blurred vision, sweating, headaches and palpitations. Her GP checked a
blood sugar during one of these episodes which was record as being
1.4 mmol/1. What is the single most useful test?
Glucagon stimulation test
Oral glucose tolerance test with growth hormone measurements
Insulin + C-peptide levels during a hypoglycaemic episode
Sh art ACTH test
Insulin tolerance test
Submit answer
Reference ranges v
Oral glucose tolerance test with growth hormone measurements
Insulin + C-peptide levels during a hypoglycaemic episode
Short ACTH test
This patient has symptoms typical of an insulinoma. Whilst supervised

fasting is normally the investigation of choice if this option is not given
then insulin + C-peptide levels during an acute hypoglycaemic episode
are useful.
,t If t9 Discuss (1) Improve ]
Next question )
Next question >
lnsulinoma
An insulinoma is a neuroendocrine tumour deriving mainly from

pancreatic Islets of Langerhans cells
Basics
• most common pancreatic endocrine tumour
• 10% malignant, 10% multiple
• of patients with multiple tumours, 50% have MEN-1
Features
• of hypoglycaemia: typically early in morning or just before meal,
e.g. diplopia, weakness etc
• rapid weight gain may be seen
• high insulin, raised proinsulin:insulin ratio
• high C-peptide
Diagnosis
• supervised, prolonged fasting (up to 72 hours)
• CT pancreas
Management
• surgery
• diazoxide and somatostatin if patients are not candidates for
surgery
Next question )
Q4
A 60-year-old man who is known to have lung cancer comes for review.
For the past three weeks he has lost his appetite, has been feeling sick
and generally feels tired. On examination he appears to be mildly
dehydrated. You order some blood tests:
Calcium 3.12 mmol/I
Albumin 40 g/ I
Glucose (random) 6.7 mmol/I
Urea 10.2 mmol/1
Which one of his existing medications is most likely to be contributing

to his presentation?
Amlodipine
Simvastatin
Bendroflu methiazide
Aspirin
Lisinopril
Submit answer
Simvastatin
Bendroflumethiazide
Aspirin
Lisinopril
Thiazides cause hypercalcaemia

Importance: 50
16 .. • Discuss Improve
Next question )
- -.... ......., .....""!II,.....- - --,-- . .,
Next quest ion )
Hypercalcaemia: causes
Two condit ions accou nt for 90% of cases of hypercalcaemia:

• 1. Primary hyperparathyroidism: comm onest cause in non-
hospitalised patien ts
• 2. Malignancy: the comm onest ca use in hospit alised patien ts.
This may be due to numb er of processes, including; bone
metastases, myeloma, PTHrP from squam ous cell lung cance r
Other causes include

• sarco idosis *
• vitamin D intoxic ation
• acromegaly
• thyrotoxicosis
• Milk-alkali syndrome
• drugs: thiazides, calciu m contai ning antac ids
• dehydration
• Addison's disease
• Paget's disease of the bone* *
*other causes of granulomas may lead to hypercalcaemia e.g.

Tuberculosis and histop lasmo sis
**usually normal in this condi tion but hypercalcaemia may occur with
prolonged immob ilisatio n
Next quest ion )

QS
A 40-year-old man presents to the GP concerned about his risk of

developing cancer. You notice that he has large spade-like hands, a
prominent forehead and nose, and thick skin. Which of the following
cancers is he at increased risk of developing?
Pancreatic carcinoma
Colorectal carcinoma
Adrenal carcinoma
Malignant melanoma
Lung cancer
Submit answer
Reference ranges v
Colorectal carcinoma ]
Adrenal carcinoma
Malignant melanoma
Lung cancer
Patients with acromegaly have an increased risk of colorectal

carcinoma
Importance: 50
Patients with acromegaly have an increased incidence of colorectal

polyps and carcinoma. This is a fairly recent finding, now that patients
with acromegaly are surviving longer due to better management of their
other complications, particularly diabetes and cardiovascular disease. It
is recommended that patients with acromegaly have an initial
colonoscopy at age 40, and enter a surveillance program based on the
resu lts of the colonoscopy.
Guidelines for colorectal cancer screening and surveillance in moderate

and high risks. Update
https:// www.ncbi.nlm.nih.gov/pubmed/20427401
[ ,. ,. - Discuss Improve ]
Next question )
In acromegaly 1there is excess growth hormone secondary to a pituitary

Features
hypertrophy
• raised prolactin in 1/ 3 of cases - galactorrhoea
Complications
• hypertension
• diabetes (>10%)
• cardiomyopathy
Next question )
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~
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Q6
A 23-year-old woman is diagnosed with Graves' disease. Which one of

the following statements regarding treatment is correct?
Block-and-replace regimes are usually of a shorter duration than

carbimazole titration therapy
Concurrent administration of propranolol and carbimazole should

be avoided
Patients on block-and-replace regimes have fewer side-effects

than those using titration therapy
Carbimazole should be started at no higher than 1Omg/ day for

patients commencing a titration regime
In the block-and-replace regime levothyroxine should be started

at the same time as carbimazole
'
Submit answer
Reference ranges v
A 23-year-old woman is diagnosed with Graves' disease. Which one of
the following statements regarding treatment is correct?
Block-and-replace reg imes are usually of a shorter duration than

carbimazole titration therapy
Concurrent administration of propranolol and carbimazole should be

avoided
Patients on block-and-replace regimes have fewer side-effects than

those using t itration therapy
Carbimazole should be started at no higher than 1Omg/ day for

patients commencing a titration regime
In the block-and-replace regime levothyroxine should be started at

the same time as carbimazole
a6 •• - Discuss (6) Improve
Next question )
Graves' disease: ma nag em ent
al
Despite man y trials there is no clea r guid ance on the optim
de titra tion of
man agem ent of Graves' dise ase. Trea tmen t optio ns inclu
k-and-replace
anti-thyroid drugs (ATDs, for exam ple carbimazole), bloc
is ofte n given
regimes, radioiodine trea tmen t and surgery. Propranolol
initially to bloc k adrenergic effe cts
ATD titra tion

to main tain
• carbimazole is start ed at 40m g and reduced grad ually
euthyroidism
• typic ally continued for 12-18 mon ths
show n to
• patie nts follo wing an ATD titra tion regim e have been
e
suffe r fewe r side -effe cts than thos e on a bloc k-and-replac
regime
Block-and-replace
• carbimazole is start ed at 40m g
• thyroxine is added when the patie nt is euthyroid
• trea tmen t typic ally lasts for 6-9 mon ths
nulo cyto sis

The majo r com plica tion of carb imaz ole ther apy is agra
Radioiodine trea tmen t

for 4-6
• cont raind icati ons include pregnancy (should be avoided
eye
mon ths follo wing trea tmen t) and age < 16 years. Thyr oid
the
disease is a relative cont raind icati on, as it may wors en
cond ition
nds on
• the prop ortio n of patie nts who beco me hypothyroid depe
require
the dose given, but as a rule the majo rity of patie nt will
thyroxine supp leme ntati on afte r 5 years
Nex t ques tion )
CamScanne r ➔ •..;~ L - ~1
Q7
Which one of the following is least associat ed with gynaecomastia?
Seminoma
Liver disease
Puberty
Hypothyroidism
Submit answer
Reference ranges v
Seminoma
Liver disease
Puberty
Hypothyroidism
Gynaecomastia is seen in up to a third of men with thyrotoxicosis, but is

not a feature of hypothyroidism
[ "' .. • Discuss (1) Improve ]
Next question )
Gynaecomastia

causes of gynaecomastia
• syndromes with androgen deficiency: Ka llman's, Klinefelter's
• liver disease
• hyperthyroidism
• haemodialysis

• cimetidine
• digoxin
• cannabis
• finasteride

• tricyclics
• isoniazid
• heroin
• busulfan
• methyldopa
Next question )
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Q8
A 25-year-old woman presents for her first cervical smear. What is the
most important aetiological factor causing cervical cancer?
Human papilloma virus 6 & 11
Herpes simplex virus 2
Smoking
Combined oral contraceptive pill use
Submit answer
Reference ranges v
Herpes simplex virus 2
Smoking
Combined oral contraceptive pill use
Cervical cancer: Human papillomavirus infection (particularly

16,18 & 33) is by far the most important risk factor
Importance: 50
Whilst a number of the above are known to contribute to the

development of cervica l cancer infection with human papilloma virus 16
& 18 is by far the most important factor.
116 .. • Discuss (1) Improve
Next question )
Cervical cancer
Around 50% of cases of cervical cance r occur in wome n under the age
of 45 years, with incidence rates for cervical cance r in the UK are
highes t in people aged 25-29 years, accord ing to Cancer Research UK. It
may be divided into:
• squam ous cell cancer (80%)
• adenocarcinoma (20%)
Features
• may be detected during routine cervical cance r screen ing
• abnormal vaginal bleeding: postco ital, interm enstru al or
postm enopa usal bleeding
• vaginal discharge
Human papillomavirus (HPV), partic ularly serotypes 16,18 & 33 is by far

the most impor tant factor in the develo pmen t of cervical cancer. Other
risk factor s include:
• smoki ng
• human immun odefic iency virus
• early first intercourse, many sexual partne rs
• high parity
• lower socioe conom ic status
• combi ned oral contra ceptiv e pill*
Mecha nism of HPV causin g cervical cance r

• HPV 16 & 18 produces the oncog enes E6 and E7 genes
respectively
• E6 inhibit s the p53 tumou r suppr essor gene
• E7 inhibit s RB suppr essor gene
*the strength of this assoc iation is some times debated but a large
study published in the Lancet (2007 Nov 10;370 (9599 ):1609-21)
confir med the link
0 Q9
A 45-year-old man is reviewed in the diabetes clinic. The following

results are obtained:
Urinalysis NAO
HbA1 c 69 mmol/ mol
Gliclazide is added to the metformin he already takes. What is the

minimum time period after which the HbA 1c should be repeated?
6 months
1 month
2 weeks
3 months
4 months
Submit answer
Reference ranges v
13months
4 month s
A more accurate answe r would proba bly be 2 month s but this is not
given as an option . See the explan ation below
[ ,t 'f • Discuss (4) Impro ve ]
Next quest ion )
Glycosylated haemoglobin
Glycosylated haemo globin (HbA1c) is the most widely used measu re of

long-t erm glycae mic contro l in diabet es mellitu s. HbA1 c is produ ced by
the glycos ylation of haem oglobi n at a rate propo rtiona l to the gluco se
conce ntratio n. The level of HbA 1c theref ore is depen dant on
• red blood cell lifespan
• average blood glucos e conce ntratio n
A numb er of condit ions can interfe re with accur ate HbA 1c

interp retatio n:
Lower-than-expected levels of Highe r-than -expe cted levels of

HbA1 c ( due to reduced red HbA1 c (due to increased red
blood cell lifespan) blood cell lifespan)
Sickle-cell anaemia Vitam in 812/ folic acid

GP6D deficie ncy deficie ncy
Hereditary spher ocytos is Iron-d eficien cy anaemia
Splen ectom y
over the
HbA1c is generally thou ght to refle ct the bloo d gluc ose
is weig hed mor e
previous '3 mon ths' altho ugh ther e is som e evidence it
mme nd
stron gly to gluc ose levels of the past 2-4 weeks. NICE reco
then 6 mon thly' .
'HbA 1c shou ld be chec ked every 3-6 mon ths until stable,
ose is com plex

The relationship between HbA 1c and average bloo d gluc
tions Trial
but has been studied by the Diabetes Control and Com plica
repo rting HbA1c
(DCCT). A new inter natio nally stan dard ised meth od for
cal
has been developed by the International Federation of Clini
of
Chemistry (IFCC). This will repo rt HbA 1c in mm ol per mol
haem oglo bin with out gluc ose attac hed.
HBA 1c Average plas ma gluc ose

(%) (mm ol/I) IFCC -HbA1 c (mm ol/m ol)
5 5.5
6 7.5 42
7 9.5 53
8 11 .5 64
9 13.5 75
10 15.5
11 17.5
12 19.5
= (2 * HbA 1c)
From the above we can see that average plas ma gluc ose
-4.5

Q10
Dynamic pituitary function tests may be used to assess each one of the
following, except:
Cortisol
Prolactin
Growth hormone
Follicular stimulating hormone
Antidiuretic hormone
Submit answer
Reference ranges v
I Antldi uretic hormo ne
[ ,6 ,. tit Discuss (4) Impro ve ]
Next quest ion )
Dynamic pituitary function tests
A dynam ic pituita ry functi on test is used to asses s patien ts with

suspe cted prima ry pituita ry dysfun ction
Insulin, TRH and LHRH are given to the patien t follow ing which the
serum glucose, cortiso l, growt h hormo ne, TSH, LH and FSH levels are
recorded at regular interva ls. Prolactin levels are also some times
measu red*
A norma l dynam ic pituita ry functi on test has the follow ing

chara cterist ics:
• GH level rises > 20mu / l
• cortis ol level rises > 550 mmol/1
• TSH level rises by> 2 mu/ I from baseli ne level
• LH and FSH should doubl e
*dopa mine antag onist tests using metoc lopram ide may also be used in
the invest igation of hyper prolac tinaem ia. A norma l respo nse is at least
a twofo ld rise in prolactin. A blunte d prolac tin respo nse sugge sts a
prolac tinoma
Next question )
Q11
A 49-year-old man with type 2 diabetes mellitus is reviewed. Despite

weight loss and therapy with metformin and gliclazide his last HbA 1c is
7.2%. Which one of t he following factors would suggest that the patient
may benefit from a meglitinide?
Obesity
Not adhering to diabetic diet
Problems with hypoglycaemia from gliclazide
Erratic lifestyle
Elderly and frail patients
Submit answer
Reference ranges v
Erratic lifestyle
Elderly and frail patients
Meglitinides - stimulate insulin release - good for erratic lifestyle

Importance: 50
Meglitinides stimulate insulin release and are particularly useful for

post-prandial hyperglycaemia or an erratic eating schedule, as patients
take them shortly before meals
•• .. tt Discuss (7) Improve
Next question )

• HbA 1 c targets have changed. They are now dependent on what
frailty

lifestyle changes to aim for a HbA1c of 48 mmol/mol (6. 5%), but
should only add a second drug if the HbA 1 c rises to 58 mmol/mol
(7.5%)
Dietary advice
carbohydrates
• control the intake of foods containing saturated fats and t rans
fatty acids
diabetes
• initial target weight loss in an overweight person is 5-1 0%
HbA1c targets

motivation
• HbA1c should be checked every 3-6 months until stable, then 6
monthly
• in 207 5 the guidelines changed so HbA1 c targets are now
Lifestyle or single drug treatme nt
HbA1c
target
Manage ment of T2DM
48
Lifestyle
mmol/ mol
(6.5%)
Lifestyle + metform in 48
mmol/m ol
(6.5%)

(e.g. lifestyle + sulfonylurea) mmol/m ol
(7.0%)
Practical examples
• a patient is newly diagnosed with HbA 1 c and wants to try lifestyle
treatme nt first. You agree a target of 48 mmol/m ol (6.5%)
• you review a patient 6 months after starting metform in. His
HbA 1 c is 51 mmol/m ol (6.8%). You increase his metform in from
Patient already on treatme nt
Manage ment of T2DM HbA1c target
Already on one drug, but HbA1 c has risen to 58 53 mmol/ mol

mmol/m ol (7.5%) (7.0%)
Drug treatment

can't:
Mettormtn not tolerated or e1

M4tform n
• if the HbA1c has risen to 58 mmol/ mol (7.5%) then a second drug
• - sulfonylurea
• - gliptin
• - pioglitazone
• if despite this the HbA1 c rises to, or remains above 58 mmo l/mo l
(7.5%) then triple therapy with one of the follow ing comb inatio ns
should be offered:
• -+ metfo rmin + glipti n + sulfo nylur
ea
• -+ metfo rmin + piogl itazo ne + sulfo
nylurea
• -+ metfo rmin + sulfo nylur ea + SGLT
-2 inhib itor
• - metfo rmin + pioglitazone + SGLT-2 inhib itor
Criteria for glucagon-like peptide1 (GLP1) mime tic (e.g. exenatide)

• if triple therapy is not effective, not tolera ted or contr aindi cated
then NICE advise that we cons ider comb inatio n thera py with
metfo rmin, a sulfonylurea and a gluca gonli ke peptide1 (GLP1)
mime tic if:
• BMI >= 35 kg/ m 2 and spec ific psyc holog ical or othe r medi cal
-+
problems associated with obes ity or

• - BMI < 35 kg/ m and for whom insulin therapy woul d have
2
signi fican t occu patio nal impli catio ns or
weight loss would benefit other signi fican t obesityrelated como rbidit ies
• only continue if there is a reduction of at least 11 mmo l/mo l
[1 .0%] in HbA1c and a weig ht loss of at least 3% of initial body
weig ht in 6 mont hs
Practical examples
• you review an established type 2 diabe tic on maxi mum dose
metfo rmin . Her HbA 1c is 55 mmo l/ mol (7.2%). You do not add
another drug as she has not reached the thres hold of 58
mmo l/ mol (7.5%)
• a type 2 diabetic is found to have a HbA 1c of 62 mmo l/mo l (7.8%)
at annual review. They are currently on maxi mum dose metfo rmin.
• if the HbA1crises to 48 mmol /mol (6.5%) * on lifesty le
interventions, consid er one of the follow ing:
• _. sulfonylurea
• _. gliptin
• _. pioglitazone
• if the HbA 1c has risen to 58 mmol / mol (7.5%) then a one of the
follow ing combi nation s should be used:
• _. gliptin + pioglitazone
• -+ gliptin + sulfon ylurea
• _. pioglitazone + sulfonylurea
• if despite this the HbA 1c rises to, or remains above 58 mmol /mol
(7.5%) then consid er insulin therapy
Starting insulin
• metfo rmin should be contin ued. In terms of other drugs NICE
advice : 'Review the contin ued need for other blood glucos e loweri ng
therapies '
• NICE recommend startin g with huma n NPH insulin (isophane,
intermediate acting) taken at bed-tim e or twice daily accor ding to
need
Blood pressure
• target is< 140/8 0 mmHg (or< 130/ 80 mmHg if end-organ
damage is present)
Antiplatelet s
• should not be offered unless a patien t has existin g cardio vascu lar
disease
Lipids
• following the 2014 NICE lipid modifica tion guidelines only patients
with a 10-year cardiova scular risk > 10% (using QRISK2) should be
offered a statin. The first-line statin of choice is atorvast atin 20mg
on
Prtmary p,wventton Sec~ry prevention
10.,..,~1A afrisi••1 OR t.nown CNwtOIMeM

masl~1 ~0ft ~iat.._OR
CKD I eQfR c ~ papal ............
Atorvastatln 20mg od
Atorvastatin IOmg od
non-HOL nn noc t by .,. ,o,. tnen
cCtlllder wnng I.IP IO 81),,g
-kthis is a bit confusin g because isn't the diagnos tic criteria for T2DM
HbA 1c 48 mmol/m ol (6.5%)? So shouldn 't all patients be offered
metform in at diagnosis? Our interpret ation of this is that some patients
upon diagnos is will elect to try lifestyle measures, which may reduce
their HbA 1c below this level. If it then rises to the diagnos tic threshol d
again metform ln should be offered
Next question )
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0 Q12
Which of the fo llowing statements is true regarding the

pathophysiology of diabetes mellitus?
Concordance between identical twins is higher in type 2 diabetes

mellitus than type 1
Patients with type 1 diabetes mellitus are rarely HLA-DR4 positive
Type 2 diabetes mellitus is associated with HLA-DR3
Haemochromatosis is an example of primary diabetes
Type 1 diabetes mellitus is thought to be inherited in an

autosomal dominant fashion
Submit answer
Reference ranges v
Concordance between identical twins is higher in type 2 diabetes
mellitus than type 1
Patients with type 1 diabetes mellitus are rarely HLA-DR4 posiitive
Type 2 diabetes mellitus is associated with HLA-DR3
Haemochromatosis is an example of primary diabetes
Type 1 diabetes mellitus is thought to be inherited in an autosomal

dominant fashion
Type 1 diabetes mellitus is caused by autoimmune destruction of the

Beta-cells of the pancreas. Identical twins show a genetic concordance
of 40%. It is associated with HLA-DR3 and DR4. It is inherited in a
polygenic fashion
Type 2 diabetes mellitus is thought to be caused by a relative deficiency

of insulin and the phenomenon of insulin resistance. Age, obesity and
ethnicity are important aetiological factors. There is almost 100%
concordance in identical twins and no HLA associations.
Haemochromatosis is an example of secondary diabetes
[ ,. ,. - Discuss (3) Improve ]
Next question )
Next question )
Diabetes: pathophysiology
Type 1 OM
• autoimmune disease
• antibodies against beta cells of pancreas
• HLA OR4 > HLA DR3
• various antibodies such as islet-associated antigen (IAA) antibody
and glutamic acid decarboxylase (GAD) antibody are detected in
patients who later go on to develop type 1 OM - their prognostic
significance is not yet clear
Next question )
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Q13
Liddle's syndrome is associated with each one of the following, except
Alkalosis
Response to treatment with amiloride
Hypertension
Hypokalaemia
Submit answer
Reference ranges v
Response to treatment with amiloride
Hypertension
Hypokalaemia
•• f
11
• Discuss (1) Improve
Next question )
Liddle's syndrome
Liddle's syndrome is a rare autosomal dominant condition that causes

hypertension and hypokalaemic alkalosis. It is thought to be caused by
disordered sodium channels in the distal tubules leading to increased
reabsorption of sodium.
Treatment is with either amiloride or triamterene
Next question >
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Q14
Which one of the following types of thyroid cancer is associated with

the RET oncogene?
Anaplastic
Lymphoma
Follicular
Medullary
All types of thyroid cancer
Submit answer
Reference ranges v
Medullary
All types of thyroid cancer
The RET oncogene encodes a receptor tyrosine kinase and is

associated with MEN type 2.
Papillary thyroid cancer also appears to be associated with the RET

oncogene
116 f
11 tt Discuss Improve
Next question >
Multiple endocrine neoplasia
The table below summarises the three main types of multiple endocrine
neoplasia (MEN). MEN is inherited as an autosomal dominant disorder.
MEN type I MEN type Ila MEN type llb
Medullary thyroid Medullary thyroid

3 P's
cancer (70%) cancer
Parathyroid (95%):
hyperparathyroidism 2 P's 1P
due to parathyroid
hyperplasia Parathyroid (60%) Phaeochromocytomc
Pituitary (70%) Phaeochromocytoma
Pancreas (50%): e.g. Marfanoid body
insulinoma, habitus
gastrinoma (leading Neuromas
to recurrent peptic
ulceration)
Also: adrenal and
thyroid
MENl gene RET oncogene RET oncogene
Most common
presentation =
hypercalcaemia
MEN type 1
P oc, he tumours
(e g gastnnoma
su!inoma)
Pitultary tumours
<• g PfO cunornaJ
Primary
hyperparathyroidrsm
MEN type 2a MEN type 2b
PhaeocPuomocytoma
Medullaiy thyroid
ca!lCer
Neuromas
RE T oncogene
Venn diagram showing the different types of MEN and their

associated features
Next question )
B J ~ A ...
Q15
A 30-year-old female is started on carbimazole 20mg bd following a

diagnosis of Grave's disease. What is the best biochemical marker to
assess her response to treatment?
Total T4
TSH
Free T4
ESR
Free T3
Submit answer
Reference ranges v
Free T4
ESR
Free T3
The answer the College are loo kin g for is TSH

. The re is how eve r a
sig nifi can t proportion of pat ien ts for wh om
TSH mo nito ring alo ne is
insufficient. TSH ma y remain suppressed for
several we eks as
continued production of thy roid stim ula ting
imm uno glo bul ins seen in
Grave's disease reduces the need for the pitu
itar y to sec rete TSH
[ ,. •• tt Discuss (7) Imp rov e ]
Ne xt que stio n )
Thyrotoxicosis: causes and investigation
Graves' disease accounts for around 50-60%of cases of thyrotoxicosis.
Causes
• Graves' disease
• toxic nodular goitre
• acute phase of subacute (de Quervain's) thyroiditis
• acute phase of post-partum thyroiditis
• acute phase of Hashimoto's thyroiditis (later results in
hypothyroidism)
• amiodarone therapy
Investigation
• TSH down, T4 and T3 up
• thyroid autoantibodies
• other investigations are not routinely done but includes isotope
scanning
Hypothyroidism Hyperthyrodism
H st11moo's
Chyroidi,:,s &lblacute th~roicl t.s
(de Ouervarn's) Graves' disease
Ill
Amiodarone Toxic muttinodular goitre

RI S lhyroid1lJS
Postpartum thYf01di1L~

Q16
A 24-year-old female with a history of type 1 diabetes mellitus presents

to the Emergency Department with vom iting and abdominal pain.
Finger-prick testing estimates the blood sugar to be 25 mmol/1. Arterial
blood gases record a pH of 7.22. On examination the patient is
dehydrated and weighs 80 kg . An intravenous line is sited and bloods
are sent. One litre of 0.9% saline is infused and an intravenous insulin
pump is set-up . What rate should insulin be initially given?
1O unit / hour
1 unit / hour
2 unit / hour
6 unit / hour
8 unit / hour
Submit answer
Reference ranges v
I 8 unit/ hour
The Joint British Diabetes Societies produced guidelines in 201 0

recommending starting the insulin infusion at a rate of 0.1 unit/kg/hour.
Next question )
Diabetic ketoacidosis (DKA) may be a complication existing type 1

2 diabetes mellitus may also develop DKA.
Whilst DKA remains a serious condition mortality rates have decreased

from 8% to under 1% in the past 20 years.
Pathophysiology
• DKA is caused by uncontrolled lipolysis (not proteolysis) which
The most common precipitating factors of DKA are infection, missed

Features
• abdominal pain
Diagnostic criteria


• glucose > 13.8 • glucose > 11 mmol/ 1or known
mmol/ 1 diabetes mellitus
• pH< 7.30 • pH< 7.3
• serum bicarbonate • bicarbonate < 1 5 mmol/ 1
<18 mmol/ 1 • ketones > 3 mmol/ 1or urine
• anion gap > 1 O ketones ++ on dipstick
• ketonaemia
Management
regime below.
unit/ kg/ hour. Once blood glucose is < 15 mmol/ 1an infusion of 5%
should be stopped

BP on admission 9UmmHg and over
Fluid Volume
0.9% sodium chloride 1 L 1000ml over 1 st hour

chloride hours

chloride hours
0. 9% sodium chloride 1 L with potassium 1000ml over next 4

ch loride hours

chloride hours
0.9% sodium chloride 1 L with potassium 1 000ml over next 6

ch loride hours
18-25 years) as they are at greater risk of cerebral oedema .

hours (mmol/L) of infusion solution
Over 5.5 Nil
3.5-5.5 40

potassium needs to be given
• gastric stasis
• thromboembolism
• arrhythmias secondary to hyperkalaemia/ iatrogenic hypokalaemia
* children/ young adults are particularly vulnerable to cerebral oedema

following fluid resuscitation in OKA and often need 1 :1 nursing to
Next question )
B I = ...
- T I ...
Save my notes
Search
Q17
A 54-year-old female presents to the Emergency Department concerned

about double vision . She is noted to have exophthalmos and
conjunctiva! oedema on examination and a diagnosis of thyroid eye
disease is suspected. What can be said regarding her thyroid status?
Hyper- or euthyroid
Hypothyroid
0 Hyperthyroid
Hypo- or euthyroid
Eu-, hypo- or hyperthyroid
Submit answer
Reference ranges v
I Eu-, hypo- or hyperthyro-id~
Whilst thyroid eye disease is mostly associated with hyperthyroidism

secondary to Graves' disease there is not always an association. A
minority of patients will either be euthyroid or hypothyroid.
It is also known that the severity of thyroid eye disease is not related to
the degree of thyrotoxicosis in Graves' disease.
16 if • Discuss (4) Improve
Next question )
Thyroid eye disease

disease.
Pathophysiology
autoantigen, possibly the TSH receptor -- retro-orbital
inflammation
Prevention
disease. Prednisolone may help reduce the risk
Features
presentation
• exophthalmos
• ophthalmoplegia
Management
• steroids
• radiotherapy
• surgery

or both eyes
• disc swelling
Next question )
Q18
A 16-year-old male is reviewed in the endocrinology clinic due to lack of

pubertal development. On examination his testes are undescended and
there is only scanty pubic hair. What is the most likely diagnosis?
Down's syndrome
Kallman's syndrome
Dubin-Johnson syndrome
Turner's syndrome
Submit answer
Reference ranges v
Dubin-Johnson syndrome
Turner's syndrome
Cryptorchidism is more suggestive of Kallman's than Klinefelter's

syndrome
116 •• • Discuss (3) Improve
Next question )
Kallmann's syndrome
Kallmann's syndrome is a recognised cause of delayed puberty

secondary to hypogonadotrophic hypogonadism. It is usually inherited
as an X-linked recessive trait. Kallmann's syndrome is thought to be
caused by failure of GnRH-secreting neurons to migrate to the
hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy

with delayed puberty
Features
• 'delayed puberty'
• hypogonadism, cryptorchidism
• anosmia
• sex hormone levels are low
• LH, FSH levels are inappropriately low/ normal
• patients are typically of normal or above average height
Cleft lip/ palate and visual/hearing defects are also seen in some
Q19
Which one of the following statements regarding impaired glucose

regulation is correct?
All patient should have a repeat oral glucose tolerance test every
2 years
Patients with impaired glucose tolerance are more likely to

develop diabetes than patients with impaired fasting glycaemia
Impaired glucose tolerance (IGT) is defined as a fasting glucose

greater than or equal to 6.1 but less than 7.0 mmol/1
Around 1 in 20 adults in the UK have impaired glucose regulation
Patients should be offered pioglitazone if lifestyle changes fail to

improve their glucose profile
Submit answer
Reference ranges v
Patients with impaired glucose tolerance are more likely to develop
diabetes than patients with impaired fasting glycaemia
Impaired glucose tolerance (IGT) is defined as a fasting glucose

greater than or equal to 6.1 but less than 7.0 mmol/1
Around 1 in 20 adults in the UK have impaired glucose regulation
Patients should be offered pioglitazone if lifestyle changes fail to

improve their glucose profile
8' .. • Discuss (3) Improve
Next question >

Terminology
talking to other healthcare professionals
• a fasting plasma glucose of 6.1-6. 9 mmol/ 1or an HbA1c level of
42-47 mmol/ mol (6 .0-6.4%) indicates high risk
Fasting glucose: <= o mmol+1 >= 1.0 nnnol.11
,rediabetH
Normal g~m•c control Diabnn meliilus
.,.'bi\ le ~2....&7 rrm:,lmci 6 ~ -I
1$
or '
C: n~ g\leow 6 1-6 Pm~,
HbA1c· ,,=•s rt'mot•mot

<a •1
..mmol!mot
) I 5
I e ....,, $ eq 10 lhlS or i ~ C d gno$lC

tclo'N re com;idcred n I t,reS.~~ for o bees
Management
diet

resistance
Definitions
mmol/1 implies impaired fasting glucose (IFG)
glucose less than 7.0 mmol/1 and OGTT 2-hour value greater than
or equal to 7.8 mmol/1 but less than 11.1 mmol/1
test to rule out a diagnosis of diabetes. A result below 11 .1
mmol/1 but above 7.8 mmol/1 indicates that the person doesn't
Next question )
B I A ... ·-
·- 21-: - - ...
0 Q20
A 37-year-old lady presents with weight gain and bruising. On

examination, she is hypertensive and has proximal myopathy. A low
dose dexamethasone suppression test showed a lack of appropriate
suppression of plasma cortisol. However, cortisol was suppressed
during a high dose dexamethasone suppression test. Plasma ACTH
was elevated. A pituitary MRI was normal.
Cushing's disease
Exogenous steroid use
Small cell lung can cer
Conn's syndrome
Adrenal hyperplasia
Submit answer
Reference ranges v
Cushing's disease
Exogenous steroid use
Small cell lung cancer
Conn's syndrome
Adrena I hyperplasia
In Cushing's disease, cortisol is not suppressed by low-dose

dexamethasone but is suppressed by high-dose dexamethasone
Importance: 50
Cushing's disease is when there is an ACTH secreting pituitary

adenoma. In Cushing's disease, cortisol is not suppressed by low-dose
dexamethasone but is suppressed by high-dose dexamethasone. The
adenoma in Cushing's disease is often too small to be picked up on CT
or MRI imaging. A negative scan does not rule out this diagnosis.
There is no evidence from the history of exogenous steroid use. With

exogenous steroid use, the plasma ACTH would be decreased.
With ectopic ACTH from small cell lung cancer, cortisol would not be
suppressed by low dose or high-dose dexamethasone.
Conn's syndrome is an aldosterone secreting adrenal adenoma.
With cortisol secretion from an adrenal adenoma, cortisol would not be

suppressed by low-dose or high-dose dexamethasone.
r "' I 11
, I tt Discuss (2) I Improve l
Investigations are divided into confirming Cushing's synd rome and then
differentrate between true Cushing's and pseudo-Cushing's

Localisation tests
The first-line localisation is 9am and midnight plasma ACTH (and

cortisol) levels. If ACTH is suppressed then a non-ACTH dependent


dexamethasone primary causes, i.e. likely secondary
to corticosteroid therapy


CRH stimulation
• if pituitary source then cortisol rises
• if ectopic/adrenal then no change in cortisol
Petrosal sinus sampling of ACTH may be needed to differentiate

between pituitary and ectopic ACTH secretion
Next question )
B / A ,.. 1-
~
- - ,..
1..:1 c-:::,
01
In patients with suspected insulinoma, which one of the following is

considered the best investigation?
Oral glucose tolerance test
Early morning C-peptide levels
Supervised fasting
Submit answer
Reference ranges v
Early morning C-peptide levels
Supervised fasting
lnsulinoma is diagnosed with supervised prolonged fasting

Importance: 50
CT of the pancreas is also useful in demonstrating a lesion
[ ,6 ,. t9 Discuss (2) Improve ]
Next question )
CamScanner -! W~ :.i.;,-~ \
lnsulinoma

Basics
Features
• high C-peptide
Diagnosis
• CT pancreas
Management
• surgery
surgery
Next question )
I T l ....
0 Q2
A 32-year-old woman presents to the emergency department drowsy.

On examination, she scores 12/ 1 5 on the Glasgow coma scale.
Capillary blood glucose is 1.9 mmol/L.
Which is the first hormone secreted physiologically in this scenario?
Cortisol
Glucagon
Growth hormone
lncretin
Insulin
Submit answer
Reference ranges v
Glucagon
Growth hormone
lncretin
Insulin
Glucagon is the first hormone secreted in response to

hypoglycaemia
Importance: 50
Low blood glucose can be caused by a number of factors, including

self-administration of insulin or alcohol. The first response to
hypoglycaemia physiologically is decreased insulin secretion, followed
by glucagon secretion from alpha cells of the pancreas. This causes the
liver to convert stored glycogen into glucose, thus raising circulating
blood glucose levels.
Growth hormone and cortisol are released later in response. Addison's

disease, where cortisol production is reduced, can therefore cause
hypoglycaemia. This understanding forms the basis of the insulin
tolerance test. Here, insulin is administered to induce hypoglycaemia
and an inadequate rise in serum cortisol suggests adrenal insufficiency.
lncretins, in contrast, are hormones which stimulate a decrease in blood

glucose levels, especially after eating. One particular incretin, glucagon-
like peptide 1 (GLP-1) is used in the treatment of type 2 diabetes;
exenatide is an example of an injectable GLP-1 analogue medication.
8' 1f 49 Discuss (1) Improve
Next question )
9' 11
Next question )
Hypoglycaemia
Causes
• insulinoma - increased ratio of proinsulin to insulin
• self-administration of insulin/sulphonylureas
• liver failure
• alcohol
Other possible causes in children

• nesidioblastosis - beta cell hyperplasia
Physiological response to hypoglycaemia

• hormonal response: the first response of the body is decreased
insulin secretion. This is followed by increased glucagon
secretion . Growth hormone and cortisol are also released but later
• sympathoadrenal response: increased catecholam ine-mediated
(adrenergic) and acetylcholine-mediated (cholinergic)
neurotransmission in the peripheral autonomic nervous system
and in the central nervous system
Next question )
B /
Q3
A 55-year-old female is reviewed in the diabetes clinic. The following

Urinalysis protein+
HbA 1c 86 mmol/mol (10.0%)
What average blood glucose level for the past 2 months is this most
likely to represent?
10
11
15
There is no relation between HbA 1c and average blood glucose
Submit answer
Reference ranges v
A 55-year-old female is reviewed in the diabetes clinic. The following
Urinalysis protein +
HbA1c 86 mmol/ mol (10.0%)
What average blood glucose level for the past 2 months is this most
likely to represent?
10
11
15
There is no relation between HbA 1c and average blood glucose
[ "' •• tll Discuss (4) Improve
Next question )
Q4
A diabetic man is diagnosed as having painful diabetic neuropathy in

his feet. He has no other medical history of note. What is the most
suitable first-line treatment to relieve his pain?
Duloxetine
Sodium valproate
Carbamazepine
Referral to pain management clinic
Tramadol
Submit answer
Reference ranges v
Q4
A diabetic man is diagnosed as having painful diabetic neuropathy in

his feet. He has no other medical history of note. What is the most
suitable first-line treatment to relieve his pain?
Duloxetine
Sodium valproate
Carbamazepine
Referral to pain management clinic
Tramadol
16 1f • Discuss (1) Improve
Next question )
Diabetic neuropathy
clinical practice.

pregabalin
drugs
neuropathic pain
problems
Gastroparesis
vomiting
Chronic diarrhoea

QS
A 35-year-old female is referred to the endocrine clinic due to weight

loss and palpitations. The following results are obtained:
TSH < 0.05 mu/ I
T4 178 mmol/1
Which one of the following features would most suggest a diagnosis of

Grave's disease?
Atrial fibrillation
Lid lag
Family history of radioiodine treatment
Pretibial myxoedema
Multinodular goitre
Submit answer
Reference ranges v
Pret161al myxoedema
Multinodular goitre
Pretibial myxoedema is not seen in other causes of thyrotoxicosis and

points towards a diagnosis of Graves'
•• If tt Discuss (8) Improve
Next question )

Features

o exophthalmos
o ophthalmoplegia
o digital clubbing
Autoantibodies
Q6
A 41-year-old woman is investigated for hot flushes and night sweats.

Bloods show a significantly raised FSH level and her symptoms are
attributed to the menopause. Following discussions with the patient
she elects to have hormone replacement treatment. What is the most
significant risk of prescribing an oestrogen-only preparation rather than
a combined oestrogen-progestogen preparation?
Increased risk of venous thromboembolism
Increased risk of ovarian cancer
Increased risk of colorectal cancer
Submit answer
Reference ranges v
A 41-year-old woman is investigated for hot flushes and night sweats.
Bloods show a significantly raised FSH level and her symptoms are
attributed to the menopause. Following discussions with the patient
she elects to have hormone replacement treatment. What is the most
significant risk of prescribing an oestrogen-only preparation rather than
a combined oestrogen-progestogen preparation?
Increased risk of venous thromboembolism
Increased risk of ovarian cancer
Increased risk of colorectal cancer
HRT: unopposed oestrogen increases risk of endometrial cancer

Importance: 50
,6 11, tt Discuss (2) Improve
Next question )
Hormone replacement therapy: adverse effects
Hormone replacement therapy (HRT) involves the use of a small dose

of oestrogen (combined with a progestogen in women with a uterus) to
help alleviate menopausal symptoms.
Side-effects
• nausea
• breast tenderness
• fluid retention and weight gain
Potential complications
• increased risk of breast cancer: increased by the addition of a
progestogen
• increased risk of endometrial cancer: reduced by the addition of a
progestogen but not eliminated completely. The BNF states that
the additional risk is eliminated if a progestogen is given
continuously
• increased risk of venous thromboembol ism: increased by the
addition of a progestogen
• increased risk of stroke
• increased risk of ischaemic heart disease if taken more than 1O
years after menopause
Breast cancer
• in the Women's Health Initiative (WHI) study there was a relative
risk of 1.26 at 5 years of developing breast cancer
• the increased risk relates to duration of use
• breast cancer incidence is higher in women using combined
preparations compared to oestrogen-only preparations
• the risk of breast cancer begins to decline when HRT is stopped
and by 5 years it reaches the same level as in women who have
never taken HRT
Next question )
0 Q7
A 30-year-old woman who is investigated for obesity, hirsutism and

oligomenorrhoea is diagnosed as having polycystic ovarian syndrome
(PCOS) following an ultrasound scan. She is hoping to start a fam ily
and her doctor starts metformin to try and improve her fertility. What is
the mechanism of action of metformin in PCOS?
Stimulates the release of insulin from the pancreas
Blocks the insulin mediated development of multiple immature

follicles in the ovaries
Increases peripheral insulin sensitivity
Blocks the conversion of oestradiol to testosterone
Increases hepatic gluconeogenesis
Submit answer
Reference ranges v
Increases peripheral insulin sensitivity
Blocks the conversion of oestradiol to testosterone
Increases hepatic gluconeogenesis
The majority of patients with polycystic ovarian syndrome have a

degree of insulin resistance which in turn can lead to complicated
changes in the hypothalamic-pituitary-ovarian axis.
,t •t tt Discuss Improve ]
Next question )
Polycystic ovarian syndrome: management
Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian

age. Management is complicated and problem based partly because
the aetiology of PCOS is not fully understood. Both hyperinsulinaemia
and high levels of luteinizing hormone are seen in PCOS and there
appears to be some overlap with the metabolic syndrome.
General
• weight reduction if appropriate
• if a women requires contraception then a combined oral
contraceptive (COC) pill may help regulate her cycle and induce a
monthly bleed (see below)
Hirsutism and acne

• a COC pill may be used help manage hirsutism. Possible options
include a third generation COC which has fewer androgenic
effects or co-cyprindiol which has an anti-androgen action. Both
of these types of COC may carry an increased risk of venous
thromboembolism
• if doesn't respond to COC then topical eflornithine may be tried
• spironolactone, flutamide and flnasteride may be used under
specialist supervision
Infertility
• the management of infertility in patients with PCOS should be
supervised by a specialist. There is an ongoing debate as to
whether metformin, clomifene or a combination should be used to
stimulate ovulation
• a 2007 trial published in the New England Journal of Medicine
suggested clomifene was the most effective treatment. There is a
potential risk of multiple pregnancies with anti-oestrogen*
therapies such as clomifene. The RCOG published an opinion
paper in 2008 and concluded that on current evidence metformin
is not a first line treatment of choice in the management of PCOS
• metformin is also used, either combined with clomifene or alone,
particularly in patients who are obese
• gonadotrophins
*work by occupying hypothalamic oestrogen receptors without

activating them. This interferes with the binding of oestradiol and thus
prevents negative feedback inhibition of FSH secretion
Q8
A 68-year-old female with a background of stage four chronic kidney

disease (CKD) presents with the following blood results to the
nephrology clinic. She has had progressive CKD over many years
following a diagnosis of lgA nephropathy in her third decade.
PTH 19.1 pmol/1{1.05 - 6.83)
Adjusted ca lciu m 2.84 mmol/ 1{2.1-2.6)
What endocrine abnormality is she most likely to have given her

background?
Tertiary hyperparathyroidism
Secondary hyperparathyroidism
Multiple endocrine neoplasia 1 (MEN1)
Submit answer
Reference ranges v
Q8
A 68-year-old female with a background of stage four chronic kidney

disease (CKD) presents with the following blood results to the
nephrology cl ini c. She has had progressive CKD over many years
following a diagnosis of lgA nephropathy in her third decade.
PTH 19.1 pmol/1(1.05 - 6.83)
Adjusted calcium 2.84 mmol/1 (2. 1-2.6)
What endocrine abnormality is she most likely to have given her

background?
I Tertiary hyperparathyroidism
Multiple endocrine neoplasia 1 (MEN1)
The correct answer is tertiary hyperparathyroidism. The PTH level is

inappropriate given the high ca lcium level indicating autonomous
hypersecretion of PTH. Although such results could be possible with
primary hyperparathyroidism, the long history of renal impairment
points towards tertiary hyperparathyroidism as the hypertrophied
parathyroid glands no longer respond to serum calcium levels. Tertiary
hyperparathyroidism occurs after long t erm secondary
hyperparathyroidism.
• PTH over-secretion usually from a parathyroid adenoma
• both PTH and calcium are elevated
• surgery to remove the adenoma is the most effective treatment
• conservative measures such as bisphosphonates can be used
• occurs in chronic kidney disease typically
• can be secondary to vitamin D deficiency
• PTH released due to low calcium, high phosphate and lack of
vitamin D activation by diseased kidneys
• PTH level high with calcium levels being low or normal
• medical management primarily: phosphate binders, calcium and
vitamin D supplementation
Tertiary hyperparathyroidism
• autonomous hypersecretion of PTH due to hypertrophied
parathyroid glands
• occurs after a period of long standing secondary
hyperparathyroidism
• treatment involves parathyroidectomy
Pseudohypoparathyroidism is caused by PTH resistance and is

associated with low calcium and high PTH levels. MEN1 is a rare
hereditary disorder involving multiple types of endocrine tissue
neoplasia.
16 •• • Discuss (3) Improve
Next question )
8' f
11
- Discuss (3) Improve
Next question )
Two conditions account for 90% of cases of hypercalcaemia:

• 1. Primary hyperparathyroidism: commonest cause in non-
hospitalised patients
• 2. Malignancy: the commonest cause in hospitalised patients.
This may be due to number of processes, including; bone
metastases, myeloma, PTHrP from squamous cell lung cancer

• sarcoidosis*
• vitamin D intoxication
• acromegaly
• thyrotoxicosis
• drugs: thiazides, calcium containing antacids
• dehydration
• Paget's disease of the bonett

Tuberculosis and histoplasmosis
**usually normal in this condition but hypercalcaemia may occur with

prolonged immobilisation
Next question )
Q9
A 52-year-old woman with suspected diabetes mellitus has an oral

glucose tolerance test, following the standard WHO protocol. The
following results are obtained:
0 5.9
2 8.4
How should these results be interpreted?
Impaired fasting glucose and impaired glucose to lerance
Normal
Diabetes mellitus
Submit answer
Reference ranges v
a6 •t • Discuss (3) Improve
Next question )


• fasting glucose greater than or equal to 7.0 mmol/ 1
• random glucose greater than or equal to 11.1 mmol/1(or after 75g

Fasting glucose: <=• '-0 mmon >• 7.0 mmol·I
l"n-mabt-1"
Normal 9'Y'CHffllC Control Duioelts--.
H:!Alt Ill ~Z-H l!'mQh nel e ~,I I
0f
c., r.g g\l:oM fl I~ g mmci l
HbA1c· o .c1 rnmOllinOI >-a 41 mmollmol

(5ft) {E ,51M,)
1 o ,aluu equel lo lhG or I e cne OIIIQl"IO$- c

be low.,. COMldered norrNII thu:s."!Ob for Cl8beles •n,_..,.,...,_,
1n 20 1 1 vvAo released s□ pplementary g□ laance on tne use ot AoA Icon
• a HbA 1 c of greater than or equal to 48 mmol/mol (6.5%) is
• a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude
diabetes)
Conditions where HbA1 c may not be used for diagnosis:

• children
• HIV
A fasting glucose greater than or equal to 6.1 but less tha n 7.0 mmol/1

less than 7.0 mmol/1and OGTT 2-hour value greater than or equal to 7.8
mmol/1 but less than 11 .1 mmol/1
mmol/1 but above 7.8 mmol/1indicates that the person doesn't
Q1
What is the most common cause of primary hyperaldosteronism?
Pituitary tumour
Adrenocortical adenoma
Adrenal carcinoma
Ectopic secretion
Bilateral idiopathic adrenal hyperplasia
Submit answer
Reference ranges v
l Bilateral idiopathic adrenal hyperplasia
Bilateral idiopathic adrenal hyperplasia is the most common

cause of primary hyperaldosteronism
Importance: so
[ 8' •• t9 Discuss (1) Improve
Next question )

1
commonly caused by an adrenal adenoma, termed Conn s syndrome.
Features
• hypertension
• hypokalaemia
• alkalosis
Investigations
aldosterone)
Management
spironolactone
Q2
A 22-year-old female presents with recurrent painful oral ulceration.

Examination reveals signs of oral Candida I infection. Which one of the
following would most suggest type 1 polyglandular syndrome?
Hypocal caemia
Type II diabetes mellitus
Coeliac disease
Hypercalcaemia
Submit answer
Reference ranges v
Q2
A 22-year-old female presents with recurrent painful oral ulceration.

Examination reveals signs of oral Candida! infection . Which one of the
following would most suggest type 1 polyglandular syndrome?
I Hypocalcaemia
Type II diabetes mellitus
Coeliac disease
Hypercalcaemia
Primary hypoparathyroidism is usually the first endocrine manifestation

of type 1 autoimmune polyendocrinopathy syndrome. The contrast to
multiple endocrine neoplasia (MEN), where hyperparathyroidism is a
common finding, should be noted
The question gives a slightly atypical history as this is the upper end of
the age range in which patients would be expected to present
1
"' f • Discuss (2) Improve
Next question )
Autoimmune polyendocrinopathy syndrome
Addison's disease (autoimmune hypoadrenalism) is associated with

other endocrine deficiencies in approximately 10% of patients. There
are two distinct types of autoimmune polyendocrinopathy syndrome
(APS), with type 2 (sometimes referred to as Schmidt's syndrome) being
much more common .
APS type 2 has a polygenic inheritance and is linked to H LA DR3/ DR4.

Patients have Addison's disease plus either:
• type 1 diabetes mellitus
• autoimmune thyroid disease
APS type 1 is occasionally referred to as Multiple Endocrine Deficiency

Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive
disorder caused by mutation of AIRE1 gene on chromosome 21
Feat ures of APS type 1 (2 out of 3 needed)

• chronic mucocutaneous candldlasis (typically first feature as
young chi ld)
• primary hypoparathyroidism
Vitiligo can occur in both types
Next question )
B / !! A ...
0 Q3
An 80-year-old man is admitted with a 3 month history of gradual

decline and dizziness on standing, followed by a 3 day history of
inability to mobilise, general weakness and nausea. The medical
consultant asks you to perform a short synact hen test which returns as
normal. Which cause of adrenocortical insufficiency has not been
excluded?
Infiltration of the adrenal gland by amyloidosis
Enlarging pituitary malignancy
Haemorrhage into the adrenal gland
Autoimmune adrenal failure
Infiltration of the adrenal gland by tuberculosis
Submit answer
Reference ranges v
I Enlarging pituita ry malign ancy
Haemo rrhage into the adrenal gland
Autoim mune adrenal failure
Infiltra tion of the adrenal gland by tuberc ulosis
A norma l short synacthen test does not exclude adrenocortical

insuffi ciency due to pituita ry failure
Importance: 50
The short Synacthen test is a metho d of excluding adrenal insufficiency.

A baseline cortiso l level is taken, IV synthe tic ACTH is then
admin istered and a second cortiso l level is taken 30 minutes later. If the
cortiso l post ACTH rises to > 420 nmol/L at 30 minutes, the adrenal
response to ACTH is adequate and Addison's disease (adrenal failure)
can be excluded.
However, this excludes only primar y adrenal failure and does not
exclude cortiso l deficie ncy secondary to failure of the pituita ry to
produc e ACTH . The correc t answer is therefore pituitary failure due to
damag e by an enlarging malignancy. The other answers all cause
damag e to the adrenal gland.
NICE CKS: Addison's disease

https:/ /cks.nice.org.uk/ addisons-disease
[ " •• - Discuss (2) Improve ]
Next questi on )
Next question )

is an ACTH stimulation test (short Synacthen test) . Plasma cortisol is
measured before and 30 minutes after giving Synacthen 250ug IM.
demonstrated.

• > 500 nmol/ I makes Addison's very unlikely
• < 100 nmol/I is definitely abnormal
• 100-500 nmol/1 should prompt a ACTH stimulation test to be
performed

• hyperkalaemia
• hyponatraemia
• hypoglycaemia
Next question )
Save my notes
Q4
A woman presents to the emergency department with confusion. She is

found to be hypothermic with a low blood pressure and bradycardia.
After further examination and investigation, she is found to be in a
myxoedemic coma.
What is the most appropriate first-line treatment for this lady's

presentation?
Adrenaline and levothyroxine
Prednisolone and levothyroxine
Hydrocortisone and levothyroxine
Hydrocortisone and fludrocortisone
Adrenaline and hydrocortisone
Submit answer
Reference ranges v
Prednisolone and levothyroxine
Hyd rocort isone and levothyroxine
Hydrocortisone and fludrocortisone
Myxoedemic coma is treated w ith thyroxine and hydrocortisone

Importance: 50
This question is asking about a woman presenting with confusion,

bradycardia, hypotension who has been diagnosed with a myxoedemic
coma . It is asking for the first initial treatment, thus the correct answer
is hydrocortisone and levothyroxine.
Levothyroxine is used to replace the low levels of thyroid hormone

causing the patient's symptoms.
Hydrocortisone is given to treat adrenal insufficiency. Patients suffering

from a myxoedemic coma due to secondary hypothyroidism are at risk
of hypopituitarism due to the location of the lesion. Thus patients are
treated as presumed adrenal insufficiency until it has been ruled out.
8' •t tit Discuss (2) Improve ]
Next question )
Next question )
Hypothyroidism: features
General
• Weight gain
• Lethargy
• Cold intolerance
Skin
• Dry (anhydrosis), cold, yellowish skin
• Non-pitting oedema (e.g. hands, face)
• Dry, coarse scalp hair, loss of lateral aspect of eyebrows
Gastrointestinal
• Constipation
Gynaecological
• Menorrhagia
Neurological
• Decreased deep tendon reflexes
• Carpal tunnel syndrome
A hoarse voice is also occasionally noted.
Next question )
..,,. T - - •- 1- - - m •- rrT1 - r--:i

QS
A 52-year-old man has a set of fasting bloods as part of a work-up for

hypertension. The fasting glucose comes back as 6.5 mmol/1. The test
is repeated and reported as 6.7 mmol/1. He says he feels constantly
tired but denies any polyuria or polydipsia. How should these results be
interpreted?
Impaired fasting glycaemia
Suggestive of diabetes mellitus but not diagnostic
Diabetes mellitus
Normal
Submit answer
Reference ranges v
A 52-year-old man has a set of fasting bloods as part of a work-up for
hypertension. The fasting glucose comes back as 6.5 mmol/1. The test
is repeated and reported as 6. 7 mmol/1. He says he feels constantly
tired but denies any polyuria or polydipsia. How should these results be
interpreted?
Impaired fasting glycaemia
Suggestive of diabetes mellitus but not diagnostic
Diabetes mellitus
Normal
" •• tit Discuss (3) Improve ]
Next uestion)
Q6
A SS-year-old woman is investigated following an osteoporotic hip

fracture. The following results are obtained:
TSH < 0.05 mu/ I
Free T4 29 pmol/1
Which one of the following autoantibodies is most likely to be present?
TSH receptor stimulating autoantibodies
Anti-nuclear antibodies
Anti-thyroglobulin autoantibodies
Anti-microsomal antibodies
Anti-thyroid peroxidase autoantibodies
Submit answer
Reference ranges v
TSH < 0.05 mu/ I
Free T 4 29 pmol/ 1
Which one of the following autoantibodies is most likely to be present?
TSH receptor stimulating autoantibodies
Anti-nuclear antibodies
Anti-thyroglobulin autoantibodies
Anti-microsomal antibodies
Anti-thyroid peroxidase autoantibodies
TSH receptor stimulating autoantibodies (often referred to as Thyroid

Stimulating lmmunoglobulins) are almost diagnostic of Graves' disease,
the most common cause of thyrotoxicosis in the UK
[ ,6 •• • Discuss {6) Improve ]
Next question )
Next question )
Graves' disease is the most common ca use of thyrotoxicosis. It is

Features

o exophthalmos
o ophthalmoplegia
o digital clubbing
Autoantibodies
Next question )
Q7 jc::J
A 54-year-old woman presents to the Emergency Depart ment with

confusion and fever. She has a past history of thyrotoxicosis previously
treated with radioiodine therapy. On examination she has a pulse of
120/ min regular, blood pressure 150/ 90 mmHg, temperature of 39.1°c
and a respiratory rate of 18/ min. Examination of the cardiorespiratory
system is unremarkable and urine dipstick is clear. Blood results
showed the following:
Free T4 84 pmol/ 1(normal range 10-22 pmol/1)
Free T3 29 pmol/ 1(2.5-5.5 pmol/1)
TSH < 0.01 mU/1 {0.5-4.0 mU/ 1)
Which one of the following does not have a role in the subsequent
management?
Lugol's iodine
Propranolol
Propylthiouracil
Bicarbonate
Dexamethason e
Submit answer
Free T4 84 pmol/1 (normal range 10-22 pmol/ 1)
Free T3 29 pmol/1 (2.5-5.5 pmol/ 1)
TSH < 0.01 mU/1 (0.5-4.0 mU/ 1)
Which one of the following does not have a role in the subsequent
management?
Lugol 's iodine
Propranolol
Propylthiouracil
Bicarbonate
Dexamethasone
There is no indication for giving bicarbonate in this scenario.
11t If - Discuss (4) Improve ]
Next question )
Thyroid storm
Thyroid storm is a rare but life-threatening complication of

thyrotoxicosis. It is typically seen in patients with established
thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic
thyroxine excess does not usually result in thyroid storm.
Precipitating events:
• thyroid or non-thyroidal surgery
• trauma
• infection
• acute iodine load e.g. CT contrast media
Clinical features include:

• fever > 38. 5°C
• tachycardia
• confusion and agitation
• nausea and vomiting
• hypertension
• heart failure
• abnormal liver function test - jaundice may be seen clinica lly
Management:
• symptomatic treatment e.g. paracetamol
• treatment of underlying precipitating event
• beta-blockers: typically IV propranolol
• anti-thyroid drugs: e.g. methimazole or propylthiouracil
• Lugol's iodine
• dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to
T3
Next question )
'Y
R 1 •
Q8
A 33-year-old woman is referred to the endocrinology clinic with

thyrotoxicosis. Recent blood tests show the following:
TSH < 0.05 mu/I
Free T 4 25 pmol/1
Anti-thyroid peroxidase antibodies 115 IU/ml (< 35 IU/ ml)
A smooth, non-tender goitre is noted on examination the neck. The

patient also has exophthalmos although there is no ophthalmoplegia,
no reduction in visual acuity and no eye symptoms present.
Carbimazole
Propranolol
Fine need le aspiration biopsy of the thyroid gland
Intravenous corticosteroids
Submit answer
Carbimazole
Propranolol
Fine needle aspiration biopsy of the thyroid gland
Intravenous corticosteroids
This patient has Graves' disease as evidenced by the thyrotoxicosis,

goitre, thyroid eye disease and anti-thyroid peroxidase antibodies.
Radioiodine treatment should be avoided given the presence of thyroid

eye disease so carbimazole is a better treatment option.
If her eye disease was severe then an ophthalmologist should be

consulted. Options for severe thyroid eye disease include systemic
steroids and radiotherapy.
9' f
11 _. Discuss (3) Improve
Next question )
Graves' disease: management
Despite many trials there is no clear guidance on the optimal

management of Graves' disease. Treatment options include titration of
anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace
regimes, radioiodine treatment and surgery. Propranolol is often given
initially to block adrenergic effects
ATD titration
• carbimazole is started at 40mg and reduced gradually to maintain
euthyroidism
• typically continued for 12-18 months
• patients following an ATD titration regime have been shown to
suffer fewer side-effects than those on a block-and-replace
regime
Block-and-replace
• carbimazole is started at 40mg
• thyroxine is added when the patient is euthyroid
• treatment typically lasts for 6-9 months
The major complication of carbimazole therapy is agranulocytosls
• contraindications include pregnancy (should be avoided for 4-6
months following treatment) and age < 16 years. Thyroid eye
disease is a relative contraindication, as it may worsen the
condition
• the proportion of patients who become hypothyroid depends on
the dose given, but as a rule the majority of patient will require
thyroxine supplementation after 5 years
Next question )
Q9
You are conducting the annual review of a 44-year-old woman who has
type 1 diabetes mellitus. You want to assess for diabetic neuropathy
affecting the feet.
What is the most appropriate screening test to use?
A standardi sed questionnaire
Doppler flow studies of the dorsalis pedis pulse
Nerve conduction studies
Test sensation using cotton wool
Test sensation using a 1O g monofilament
Submit answer
Reference ranges v
Test sensation using cotton wool
Test sensation using a 1o g monofllament
A 10 g monofilament should be used to assess for diabetic

neuropathy in the feet
Importance: 50
16 •• tt Discuss (1) Improve
Next question )
Diabetic foot disease
Diabetic foot disease is an important complication of diabetes mellitus

which should be screen for on a regular basis. NICE produced
guidelines relating to diabetic foot disease in 2015.
It occurs secondary to two main factors:

• neuropathy: resulting in loss of protective sensation (e.g. not
noticing a stone in the shoe), Charcot's arthropathy, dry skin
• peripheral arterial disease: diabetes is a risk factor for both macro
and microvascular ischaemia
Presentations
• neuropathy: loss of sensation
• ischaemia: absent foot pulses, reduced ankle-brachia! pressure
index (ABPI), intermittent claudication
• complications: calluses, ulceration, Charcot's arthropathy,
cellulitis, osteomyelitis, gangrene
All patients with diabetes should be screened for diabetic foot disease
on at least an annual basis
• screening for ischaemia: done by palpating for both the dorsalis
pedis pulse and posterial tibial artery pulse
• screening for neuropathy: a 1o g monofllament is used on various
parts of the sole of the foot
NICE recommend that we risk stratify patients:
Moderate
Low risk risk High risk
• no risk • deformity • previous ulceration or

factors except or • previous amputation or
callus alone • • on renal replacement therapy or
neuropathy • neuropathy and non-critical limb
or ischaemia together or
• non- • neuropathy in combination with
critical limb callus and/ or deformity or
ischaemia. • non-critical limb ischaemia in
combination with callus and/or
deformity.
All patients who are moderate or high risk (I.e. any problems other than
simple calluses) should be followed up regularly by the local diabetic
foot centre.
Next question )
B / ~ A .... :: E = .... T I.... fill .... ~ e:-:>
Save my notes J
A 39-year-old woman is reviewed in the clinical pharmacology clinic
following referral by her GP for management of her hypertension. She
has a blood pressure of 159/ 90 mmHg despite 3 oral anti-hypertensive
medications including full dose ramipril. Examination in t he clinic
confirms the elevated blood pressure. Her pulse is 72 and regu lar. Her
chest is clear and her abdomen is soft and non-tender with no palpable
masses. Her body mass index is 28 kg/ m 2 •
Hb 130 g/ 1
Platelets 221 * 109/I
WBC 6.0 * 109 /1
Na+ 141 mmol/I
K+ 3.1 m mol/I
Bicarbonate 31 mmol/I
Urea 4.1 m mol/I
Creat inine 102 µmol/I
Calcium 2.45 mmol/ I
CT abdomen: Right adrenal adenoma, thick walled gallbladder with a

solitary stone
Which of the following is the most likely diagnosis?
Conn's syndrome
Cushing's syndrome
Essential hypertension
Phaeochromocytoma
Renal artery stenosis

Conn's syndrome
Cushing's syndrome
Essential hypertension
Phaeochromocytoma
Renal artery stenosis
Primary hyperaldosteronism can present with hypertension,

hypernatraemia, and hypokalemia
Importance: 50
The relatively normal weight, coupled with hypertension and

hypokalaemic metabolic alkalosis fits well with a diagnosis of Conn's
syndrome, (primary hyperaldosteronism). The right adrenal adenoma is
the likely source of excess aldosterone production. In the presence of
an ACE inhibitor prescribed for hypertension, significant hypokalaemia
is very likely to be related to Conn's.
Cushing's syndrome is unlikely given that the body mass index is only
slightly elevated, and the presence of an adrenal adenoma and
biochemical abnormalities effectively rules out essential hypertension.
Phaeochromocytoma may be associated with hypokalaemia, but is
more likely to be associated with episodic hypertension associated with
bursts of catecholamine release. In renal artery stenosis, a significant
rise in creatinine would be expected in association with the introduction
of the ramipril.
116 If • Discuss (4) Improve
Next question )

Features
• hypertension
• hypokalaemia
• alkalosis
Investigations
aldosterone)
Management
spironolactone
Q11
Mr Bevan is a 52-year-old patient with type 2 diabetes. He was unable to

tolerate metformin due to nausea. He has been doing some of his own
research into other options and suggests an SGLT-2 inhibitor,
empagliflozin, because he has read it might help him lose weight and
improve his blood pressure, as well as improve his blood sugar.
What is the mechanism of action of this drug?
Increase insulin release from pancreas
Decrease glucose absorption in the gut
Decrease glucagon release from pancreas
Increase urinary glucose excretion
Slows gastric emptying
Submit answer
Reference ranges v
Decrease glucose absorption in the gut
Decrease glucagon release from pancreas
Increase urinary glucose excretion
SGLT-2 inhibitors work by increasing urinary excretion of glucose

(Important as it is the cause of main side effects - increased urine
output, weight loss, UTI)
Importance: 50
Increase insulin release from pancreas - this is the mechanism of action

of sulphonylureas e.g. gliclazide.
Decrease glucose absorption in the gut - this is the mechanism of

action of acarbose, which is not routinely prescribed in the UK.
Decrease glucagon release from pancreas - DPP4-inhibitors reduce the

breakdown of incretins, which thereby decreases glucagon secretion.
SGLT-2 inhibitors such as empagliflozin work by reducing glucose

reabsorption in the proximal convoluted tubule, therefore increasing the
amount of glucose excreted in the urine. An additional 70g of glucose a
day (approximately) is excreted; as well as improving blood sugar this is
also likely to lead to weight loss, in contrast to some other diabetic
medications such as sulphonylureas and insulin which cause weight
gain. The slight diuresis caused by increased glucose excretion may
also improve blood pressure. Unfortunately, increased glucose in the
urine can also cause adverse events such as urinary tract or genital
infections.
SGLT-2 inhibitors do not slow gastric emptying.
r • I •• I • Discuss I Improve l
[ ,6 •t • Discuss Improve ]
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SGLT-2 inhibitors


monitored
Next question )
B I A ... ., _
·- 1-
~
- - ....
Save my notes
Q12
A 33-year-old white male attends his GP with a two month history of

weight loss, lethargy and polydipsia. He has a past medical history of a
thyroidectomy for Grave's disease, no significant family history and
currently takes levothyroxine. The GP does a capillary glucose
measurement, which is 18.1 mmol/ L and does a urinalysis revealing 2+
glucose and 2+ ketones. His blood pressure is 134/86mmHg. What is
the most likely diagnosis?
Type 2 diabetes mellitus
Addison's disease
Latent Autoimmune Diabetes of Adulthood
Maturity Onset Diabetes of the Young
Levothyroxine-induced diabetes mellitus
Submit answer
Reference ranges v
I Latent Autoimmune Diabetes of Adulthood
Maturity Onset Diabetes of the Young
Levothyroxine-induced diabetes mellitus
Latent autoimmune diabetes of adulthood (LADA) is a disorder in

which, despite the presence of islet antibodies at diagnosis of diabetes,
the progression of autoimmune -cell failure is slow.
In contrast to type 2 diabetes, patients are typically younger and without

an increased body habitus. In contrast to type 1 diabetes, insulin is not
usually required in the early stages of the disease.
Diagnosis may be aided through a Glutamic Acid Decarboxylase (GAD)

Autoantibodies test and evidence of other autoimmune diseases.
Levothyroxine is not associated with inducing diabetes. In patients with

diabetes starting thyroxine, doses of antidiabetic drugs including insulin
may need to be increased.
1
Addison s disease is associated with hypoglycaemia.
8' f
1 - Discuss (5) Improve
Next question )
Diabetes mellitus: a very basic introduction
Diabetes mellitus is one of the most common conditions encountered

in clinical practice and represents a significant burden on the health
systems of the developed world. It is now estimated that 8% of the total
NHS budget is now spent on managing patients with diabetes mellitus.
What is diabetes mellitus?
rised
Diabetes melli tus may be defined as a chronic cond ition char acte
by abnormally raised levels of blood glucose.
?
Why is the man agem ent of diabetes mellitus so important
wou ld
Before the advent of insulin therapy untreated type 1 diab etes
can still
usually result in death. Poorly treated type 1 diab etes mell itus
etic
result in signi fican t morb idity and mort ality (as a resu lt of diab
ent now
ketoacidosis). However, the main focu s of diabetes man agem
se,
is reducing the incidence of mac rova scula r (isch aem ic hear t disea
stroke) and micr ovas cular (eye, nerve and kidney damage)
com plica tions .
Type Notes
Type 1 Auto imm une disor der where the insul in-pr oduc ing
diabetes beta cells of the islets of Langerhans in the
mellitus pancreas are destroyed by the imm une syste m
(T1D M) This results in an abso lute defic iency of insulin
resulting in raised gluco se levels
Patients tend to develop T1 OM in child hood/ early
adult life and typic ally pres ent unwell, poss ibly in
diab etic ketoacidosis
Type 2 This is the mos t com mon cause of diab etes in the
diabetes developed world . It is caused by a relative
mellitus deficiency of insulin due to an excess of adip ose
(T2D M) tissu e. In simp le term s there isn't enough insulin to
'go around' all the excess fatty tissue, leading to
blood gluco se creeping up.
Prediabetes This term is used for patients who don't yet meet
the criteria for a formal diagnosis of T2DM to be
made but are likely to develop the condition over
the next few years . They, therefore, require closer
monitoring and lifestyle interventions such as
weight loss
Gestational Some pregnant develop raised glucose levels

diabetes during pregnancy. This is important to detect as
untreated it may lead to adverse outcomes for the
mother and baby
Maturity A group of inherited genetic disorders affecting the

onset production of insulin. Results in younger patients
diabetes of developing symptoms similar to those with T2DM,
the young i.e. asymptomatic hyperglycaemia with progression
{MODY) to more severe complications such as diabetic
ketoacidosis
Latent The majority of patients with autoimmune-related

autoimmune diabetes present younger in life. There are however
diabetes of a small group of patients who develop such
adults problems later in life. These patients are often
(LADA) misdiagnosed as having T2DM
Other types Any pathological process which damages the

insulin-producing cells of the pancreas may cause
diabetes to develop. Examples include chronic
pancreatitis and haemochromatosis.
Drugs may also cause raised glucose levels. A

common example is glucocorticoids which
commonly result in raised blood glucose levels
Symptoms and signs
The presentation of diabetes mellitus depends very much on the type:
Type 1 DM Type 2 DM
Weight loss Often picked up incidentally on

Polydipsia routine blood tests
Polyuria Polydipsia
Polyuria
May present with diabetic
ketoacidosis
• abdominal pain
• vomiting
• reduced
consciousness level
Remember that the polyuria and polydipsia are due to water being
'dragged' out of the body due to the osmotic effects of excess blood
glucose being excreted in the urine (glycosuria).
Investigations
There are 4 main ways to check blood glucose:

• a finger-prick bedside glucose monitor
• a one-off blood glucose. Th is may either be fasting or non-fasting
• a HbA1c. This measures the amount of glycosylated haemoglobin
and represents the average blood glucose over the past 2-3
months
• a glucose tolerance test. In this test, a fasting blood glucose is
taken after which a 75g glucose load is taken. After 2 hours a
second blood glucose reading is then taken
The diagnostic criteria are determined by WHO.

• fasting glucose greater than or equal to 7.0 mmol/I
• random glucose greater than or equal to 11.1 mmol/I (or after 75g

In 2011 WHO released supplementary guidance on the use of HbA 1c

for the diagnosis of diabetes:
• a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is
• a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it
is not as sensitive as fasting samples for detecting diabetes)
• it should be remembered that misleading HbA 1c results can be
caused by increased red cell turnover
f asting glucose: <a: so mmol,1 >• 7.0 mmol l
,,edabetn
Honn.al flVcNmlC control r o-...--.
HoA1c a .&;'-'T nTn:l fflCI ,e c..e ~ l
or
ea1~~ g\lCOM I! 1~ p Ml!'ICl(.I
HbA1c; <a.,r~W)
mmOlmol
I L' ~luu ~ :0 thit Of I e lne OJ,li!i)n0$'C

low are com10ered nom,ml t n r ~ for ~les

Management
The principle of managing diabetes mellitus are as follows:

• drug therapy to normalise blood glucose levels
• monitoring for and treating any complications related to diabetes
• modifying any other risk factors for other conditions such as
cardiovascular disease
Type 1 diabetes
• patients always require insulin to control the blood sugar levels.
This is because there is an absolute deficiency of insulin with no
pancreatic tissue left to stimulate with drugs
• different types of insulin are available according to their duration
of action
Type 2 diabetes
• the majority of patients with type 2 diabetes are controlled using
oral medication
• the first-line drug for the vast majority of patients is metformin
• second-line drugs include sulfonylureas, gliptins and pioglitazone.
Please see the table below for further information
• if oral medication is not controlling the blood glucose to a
sufficient degree then insulin is used
Mechanism of Main side-
Drug class action Route effects Notes
Insulin Direct Subcutaneous Hypoglycaemia Used in all

replacement for Weight gain patients with
endogenous Lipodystrophy T1 OM and some
insulin patients with
poorly controlled
T2DM
Can be
classified
according to
source
(analogue,
human
sequence and
porcine) and
duration of
action (short,
immediate, long-
acting)
CamScanner ~ Y~ 4!>~1
Metformin Increases insulin Oral Gastrointestinal First-line
sensitivity upset medication in
Decreases Lactic the managemen1
hepatic acidosis* ofT2DM
gluconeogenesis
Cannot be used
in patients with
an eGFR of< 30
ml/min
Sulfonylureas stimulate Oral Hypoglycaemia Examples

pancreatic beta Weight gain include
cells to secrete Hyponatraemia gliclazide and
insulin glimepiride
Thiazolidinediones Activate PPAR- Oral Weight gain Only currently

gamma receptor Fluid retention available
in adipocytes to thiazolidinedione
promote is pioglitazone
adipogenesis
and fatty acid
uptake
CamScanner -; Y~ b - ~ I
DPP-4 inhibitors (- Increases Oral Generally well
gliptins) incretin levels tolerated but
which inhibit increased risk
glucagon of pancreatitis
secretion
SGLT-2 inhibitors Inhibits Oral Urinary tract Typically result

(-gliflozins) reabsorption of infection in weight loss
glucose in the
kidney
GLP-1 agonists (- lncretin mimetic Subcutaneous Nausea and Typically result

tides) which inhibits vomiting in weight loss
glucagon Pancreatitis
secretion
NICE provide guidelines on how drug therapy should be used in T2DM:
Metfonnln Melformln not toteroi.ci « Cl
CamSca nner -; Y~ b - ~ I
Metformin Metformin not tolerated or Cl
Metformin Glitpln
OR
Sulfonylurea
OR
HbA1c > 58 mmovmol (7 5%) Pk>glltazone
!
t.tetformln + gllpt1n HbA1c > 58 mmovmo1 (7.5%}
OR
Metformm + sulfonyrurea
OR
Metform,n + p109htazone Ghplln • p1oghtazone
OR OR
Metformln + SGLT-2 Inhibitor Gllptm + sulfonyturea
OR
PloglttaZone + sulfonylUrea
HbA 1C > 58 mmoVmol (7 5°0)
t.tetrormtn + gllptln + su1rony1urea

OR
Metform,n • ptoglltazone + sulfonylurea HbA1c > 58 mmolmol (7 .5°0)
OR
Metformln + sulfonylurea + SGLT -2 lnh1bnor
OR
Metform,n + ploglitazone + SGLT-2 Inhibitor
Insulin
Triple therapy *nor effec(/1/e not to erated or contra nd,ca1ed·
AND
BMI >35
i
Metformln + sulfonylurea + GLP-1 mimetic C Passmed,cme corn
0 Q13
An 18-year-old girl is admitted to the Emergency Department with an

episode of sweating and dizziness. She is brought in by her f ather who
has type 2 diabetes mellitus as he is worried she may be diabetic. He
describes a number of similar episodes for the past two weeks. Her BM
on admission is 1.9 mmol/ 1so the following bloods are taken:
Plasma glucose 1.8 mmol/1
Insulin 15 mg/ ml {6-10 mg/ ml)
Prolnsulln 22% (22-24%)
C-peptide 0.15 nmol/ 1(0.2-0.4 nmol/1)
Diabetes mellitus
lnsulinoma
Nesidioblastosis
Insulin abuse
Sulfonylurea abuse
Submit answer
Reference ranges v
Insulin abuse
Sulfonylurea abuse
The raised insulin with low c-peptide level points to a diagnosis of

insulin abuse. C-peptide levels would be raised in a patient following
sulfonylurea abuse
at •• tt Discuss (5) Improve ]
Next question )
Hypoglycaemia
Causes
• insulinoma - increased ratio of proinsulln to insulin
• liver failure
• alcohol


secretion. Growth hormone and cortisol are also released but later
• sympathoadrenal response: increased catecholamine-mediated
Next uestion )
Q14
Each one of the following is associated with Pendred's syndrome,

except
Goitre
Short 4th and 5th metacarpals
Sensorineural deafness
Euthyroid status
Submit answer
Reference ranges v
Short 4th and 5th metacarpals
Sensorineural deafness
Euthyroid status
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Pendred's syndrome
Pendred is an autosomal recessive genetic disorder that is

characterised by bilateral sensorineural deafness, with mild
hypothyroidism and a goitre. The patients tend to present with
progressive hearing loss and delay in academic progression. Often
head trauma tends to make the sensorineural deafness worse, leading
to patients having to avoid contact sports.
In Pendred syndrome there is a defect in the organification of iodine,

leading to dyshormonogenesis. However thyroid symptoms in pendred
syndrome are often mild and patients are often clinical ly euthyroid,
presenting only with a goitre. Thyroid function tests are also often
normal, requiring the perchlorate discharge test to aid diagnosis.
The syndrome can be diagnosed via genetic testing (Pendred syndrome

(PDS) gene, chromosome 7), audiometry and MRI imaging to look for
characteristic one and a half turns in the cochlea, compared to the
normal two and a half turns.
Treatment is with thyroid hormone replacement and cochlear implants.

Q15
The first-line treatment in remnant hyperlipidaemia

(dysbetalipoproteinaemia) is:
Ursodeoxycholic acid
Vitamin A
Statins
Fish oil
Fibrates
Submit answer
Reference ranges v
IFibrates
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Next question )
Remnant hyperlipidaemia
Overview
• rare cause of mixed hyperlipidaemia (raised cholesterol and
triglyceride levels)
• also known as Fredrickson type Ill hyperlipidaemia, broad-beta
disease and dysbetalipoproteinaemia
• associated with apo-e2 homozygosity
• high incidence of ischaemic heart disease and peripheral vascular
disease
• thought to be caused by impaired removal of intermediate density
lipoprotein from the circulation by the liver
Features
• yellow palmar creases
• palmer xanthomas
• tuberous xanthomas
Management
• flbrates are first line treatment
Next question )
Q16 [Cl
You are on the post-take ward round reviewing a 55-year-old lady who
has been admitted with her third urinary tract infection in as many
months. Of note she is a type II diabetic patient and was commenced
on empagliflozin by her GP four months ago. You suspect recurrent
urinary tract infections secondary to her empagliflozin, a sodium
glucose co-transporter 2 inhibitor used in the treatment of type 2
diabetes mellitus. Where is its main site of action?
Early distal convoluted tubule
Collecting duct
Early prox imal convoluted tubule
Late proximal convoluted tubule
Late distal convoluted tubule
Submit answer
Reference ranges v
Early proximal convoluted tubule
Late proximal convoluted tubule
Late distal convoluted tubule

Importance: 50
In the normal kidney up to 180 grams/ day of glucose is filtered by the

renal glomerulus and virtually all of it is reabsorbed in the proximal
convoluted tubule. This reabsorption is carried out by two sodium-
dependent glucose co-transporter (SGLT) proteins, SGLT1, which
reabsorbs 10%, and SGLT2, which reabsorbs the remaining 90%. While
SGLT1 is expressed elsewhere in the body, SGLT2 is expressed solely in
the kidney, making it an attractive target for novel diabetic treatments.
To date a number of SGLT2 inhibitors have been developed. These

agents have been shown to enhance renal glucose excretion by
inhibiting renal glucose reabsorption with consequent improvements in
HbA1C and insulin resistance. Furthermore, they have been shown to
have protective effects in the progression of chronic kidney disease,
blood pressure lowering effects and reduce cardiovascular events in
high risk type II diabetic patients. To date they are they only oral
hypoglycaemic agent to demonstrate any benefit on macrovascular
outcomes in type II diabetic patients.
Important side effects to be aware of with this class of drug are genital
tract infections and euglycaemic diabetic ketoacidosis .
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• i passmedicine.com/ quest ion/ qu, * ♦ ➔ 0
SGLT-2 inhibitors


monitored
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Q17
A 71-year-old woman with a history of type 2 diabetes mellitus presents

with lethargy and polyuria. A diagnosis of hyperosmolar hyperglycaemic
state is considered. Which one of the following findings would be least
consistent with this diagnosis?
pH of 7.38
Ketones 1 + in urine
Serum osmolality of 31 O mosmol/ kg
Serum bicarbonate of 19 mmol/ I
Glucose of 45 mmol/ I
Submit answer
Reference ranges v
OCI 01 I I OJI I IOIUiilj 01 JI O I I 1031 I 101/ l(Q
Serum bicarbonate of 19 mmol/ 1
Glucose of 45 mmol/1
A trace of ketones may be found in hyperosmolar hyperglycaemic state.

Serum osmolality is typically > 320 mosmol/kg
"' If t9 Discuss (7) Improve
Next question >
Hyperosmolar hyperglycaemic state
Hyperosmolar hyperglycaemic state (HHS) is a medical emergency

which is extremely difficult to manage and has a significant associated
mortality. Hyperglycaemia results in osmotic diuresis, severe
dehydration, and electrolyte deficiencies. HHS typically presents in the
elderly with type 2 diabetes mellitus (T2DM), however the incidence in
younger adults is increasing. It can be the initial presentation of T2OM.
It is extremely important to differentiate HHS from diabetic

ketoacidosis (OKA) as the management is different, and treatment of
HHS with insulin (e.g. as part of a OKA protocol) can result in adverse
outcomes. The first 24 hours of treatment is very labour intensive so
these patients are best managed in either a medical high dependency
unit.
HHS has a higher mortality than OKA and may be complicated by

vascular complications such as myocardial infarction, stroke or
peripheral arterial thrombosis. Seizures, cerebral oedema and central
pontine myelinolysis (CPM) are uncommon but documented
complications of HHS. Whilst OKA presents within hours of onset, HHS
comes on over many days, and consequently the dehydration and
metabolic disturbances are more extreme.
Pathophys1oiogy
• Hyperglycaemia results in osmotic diuresis with associated loss
of sodium and potassium
• Severe volume depletion results in a significant raised serum
osmolarity (typically> than 320 mosmol/kg), resulting in
hyperviscosity of blood.
• Despite these severe electrolyte losses and total body volume
depletion, the typical patient with HHS, may not look as
dehydrated as they are, because hypertonicity leads to
preservation of intravascular volume.
Clinical features
• General: fatigue, lethargy, nausea and vomiting
• Neurological: altered level of consciousness, headaches,
papilloedema, weakness
• Haematological: hyperviscosity (may result in myocardial
infarctions, stroke and peripheral arterial thrombosis)
• Cardiovascular: dehydration, hypotension, tachycardia
Diagnosis
• 1. Hypovolaemia
• 2. Marked Hyperglycaemia (>30 mmol/L) without significant
ketonaemia or acidosis
• 3. Significantly raised serum osmolarity (> 320 mosmol/kg)
• Note: A precise definition of HHS does not exist, however the
above 3 criteria are helpful in distinguishing between HHS and
OKA. It is also important to remember that a mixed HHS / OKA
picture can occur.
Management
The goals of management of HHS can be summarised as follows:
• 1 . Normalise the osmolality (gradually)

• 2. Replace fluid and electrolyte losses
• 3. Normalise blood olucose (qraduallv)
Fluid replacement
• Fluid losses in HHS are estimated to be between 100 - 220 ml/kg
(e.g. 10-22 litres in an individual weighing 100 kg) .
• The rate of rehydration will be determined by assessing the
combination of initial severity and any pre-existing co-morbidities
(e.g. heart failure and chronic kidney disease). Caution is needed,
particularly in the elderly, where too rapid rehydration may
precipitate heart failure but insufficient may fail to reverse an
acute kidney injury.
• Intravenous (IV) 0.9% sodium chloride solution is the first line fluid
for restoring total body fluid .
• It is important to remember that isotonic 0.9% sodium chloride
solution is already relatively hypotonic compared to the serum in
someone with HHS. Therefore in most cases it is very effective at
restoring normal serum osmolarity.
• If the serum osmolarity is not declining despite positive balance
with O. 9% sodium chloride, then the fluid should be switched to
0.45% sodium chloride solution which is more hypotonic relative
to the HHS patients serum osmolarity
• IV fluid replacement should aim to achieve a positive balance of 3-
6 litres by 12 hours and the remaining replacement of estimated
fluid losses within the next 12 hours.
• Existing guidelines encourage vigorous initial fluid replacement
and this alone (without insulin) will result in a gradual decline in
plasma glucose and serum osmolarity. A rapid decline is
potentially harmful (see below) therefore insulin should NOT be
used in the first instance unless there is significant ketonaemia or
acidosis
• The aim of treatment should be to replace approximately 50% of
estimated fluid loss within the first 12 hours and the remainder in
the following 12 hours. However this is just a guide, and clinical
judgement should be applied, particularly in patient with co-
morbidities such as heart failure and chronic kidney disease
(which may limit the speed of correction).
Monitoring response to treatment
• The key parameter in managing HHS is the osmolality to which
glucose and sodium are the main contributors. Rapid changes of
serum osmolarity are dangerous and can result in cardiovascular
collapse and central pontine myelinolysis (CPM).
• Guidelines suggest that serum osmolarity, sodium and glucose
levels should be plotted on a graph to permit appreciation of the
rate of change. They should be plotted hourly initially.
• Not all laboratories have readily available access to serum
osmolarity measurements. If not available then a calculated
osmolarity can be estimated with 2Na + glucose + urea
• Fluid replacement alone (without insulin) will gradually lower
blood glucose which will reduce osmolality
• A reduction of serum osmolarity will cause a shift of water into
the intracellular space. This inevitably results in a rise in serum
sodium (a fall in blood glucose of 5.5 mmol/L will result in a 2.4
mmol/ L rise in sodium). This is not necessarily an indication to
give hypotonic solutions. If the inevitable rise in serum Na+ is
much greater than 2.4 mmol/ L for each 5.5 mmol/L fall in blood
glucose this would suggest insufficient fluid replacement. Rising
sodium is only a concern if the osmolality is NOT declining
concurrently.
• Rapid changes must be avoided. A safe rate of fall of plasma
glucose of between 4 and 6 mmol/hr is recommended. The rate of
fall of plasma sodium should not exceed 1 O mmol/L in 24 hours.
• A target blood glucose of between 1 O and 1 5 mmol/L is a
reasonable goal.
• Complete normalisation of electrolytes and osmolality may take
up to 72 hours.
Insulin
• Fluid replacement alone with 0.9% sodium chloride solution will
result in a gradual decline of blood glucose and osmolarity
• Because most patients with HHS are insulin sensitive (e.g. it
usually occurs in T2DM), administration of insulin can result in a
rapid decline of serum glucose and thus osmolarity.
• Insulin treatment prior to adequate fluid replacement may result in
cardiovascular collapse as the water moves out of the
intravascular space, with a resulting decline in intravascular
volume.
• A steep decline in serum osmolarity may also precipitate CPM.
• Measurement of ketones is essential for determining if insulin is
required.
• If significant ketonaemia is present (3~-hydroxy butyrate is more
than 1 mmol/L) this indicates relative hypoinsulinaemia and
insulin should be started at time zero (e.g. mixed DKA / HHS
picture). The recommended insulin dose is a fixed rate
intravenous insulin infusion given at 0.05 units per kg per hour.
• If significant ketonaemia is not present (3~-hydroxy butyrate is
less than 1 mmol/L) then do NOT start insulin.
Potassium
• Patients with HHS are potassium deplete but less acidotic than
those with DKA so potassium shifts are less pronounced
• Hyperkalaemia can be present with acute kidney injury
• Patients on diuretics may be profoundly hypokalaemic
• Potassium should be replaced or omitted as required
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Q18
A 43-year-old man is found to have a phaeochromocytoma. Which anti-

hypertensive medication should be started first?
Propranolol
Ramipril
Atenolol
Phenoxybenzamine
Doxazosin
Submit answer
Reference ranges v
Ramipril
Atenolol
Phenoxybenzamine
Doxazosin
PHaeochromocytoma - give PHenoxybenzami ne before beta-

blockers
Importance: 50
Phenoxybenzamine is a non-selective alpha-adrenoceptor ant agonist

and should be started before a beta-blocker is introduced
There is ongoing debate about the optimal medical management of

phaeochromocytoma, with the suggestion that antihypertensive
treatment regimes other than non specific alpha-blockade are just as
effective and safe. There are however no trials to provide an answer to
this question yet
16 11 f tt Discuss (7) Improve
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'
-•- - - - - •- -- - -- - - - - _._ - -- - -
Phaeochromocytoma
Phaeochromocytoma is a rare catecholamine secreting tumour. About

10% are familial and may be associated with MEN type II,
neuroflbromatosls and von Hlppel-Lindau syndrome
Basics
• bilateral in 10%
• malignant in 10%
• extra-adrenal in 10% (most common site = organ of Zuckerkandl,
adjacent to the bifurcation of the aorta)
Features are typically episodic

• hypertension (around 90% of cases, may be sustained)
• headaches
• palpitations
• sweating
• anxiety
Tests
• 24 hr urinary collection of metanephrines (sensitivity 97%*)
• this has replaced a 24 hr urinary collection of catecholamines
(sensitivity 86%)
Surgery is the definitive management. The patient must first however be

stabilized with medical management:
• alpha-blocker (e.g. phenoxybenzamine), given before a
• beta-blocker (e.g. propranolol)
*BMJ 2012; 344 doi: http://dx.doi.org/ 10.1136/ bmj.e1042 (Published

20 February 2012)
Next question )
Q19
A 48-year-old male presents to the clinic. He complains of excessive

flatulence following starting a new agent for management of his type 2
diabetes mellitus. He has no other past medical history.
What drug is most likely implicated?
Metformin
Gliclazide
Acarbose
Sitagliptin
Empagliflozin
Submit answer
Reference ranges v
Acarbose
Sitagliptin
Empagliflozin
Excessive flatulence is an extremely common side effect of

acarbose which is often poorly tolerated
Importance: 50
Acarbose is an inhibitor of intestinal alpha glucosidases, which results

in decreased absorption of starch and sucrose. Since acarbose
prevents the degradation and absorption of complex carbohydrates into
glucose, an increased carbohydrate load will be delivered to the colon.
In the colon, bacteria digest the complex carbohydrates, causing
gastrointestinal side-effects such as flatulence and diarrhoea.
Excessive flatulence is the most commonly reported side effect and is
often the reason for discontinuation of the drug.
Metformin can also cause gastrointestinal side effects, however it is

often diarrhoea rather than excessive flatulence, making acarbose the
better answer.
Gliclazide is a sulphonylurea agent. The sulfonylureas act mainly by

augmenting insulin secretion and consequently are effective only when
some residual pancreatic beta-cell activity is present; during long-term
administration they also have an extrapancreatic action. Side effects
include hypoglycaemia, cholestatic jaundice and diarrhoea.
Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. Side effects

include peripheral oedema and diarrhoea.
Empagliflozin is an inhibitor of the sodium glucose co-transporter-2

(SGLT-2). It cause increased glucose excretion in the urine which
predisposed to recurrent urinary tract infections.
T2DM medications
Drugs used
• sulphonylureas
• metformin
• alpha-glucosidase inhibitors (acarbose)
• glitazones
• insulin
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Q. Google search on "T2DM medications"

Q20
A 35-year-old female has recently been diagnosed with Addison's

disease due to autoimmune adrenal failure after presenting with a 3-
month history of lethargy, nausea, weight loss and fainting. Which of the
following physical signs may you find in this patient?
Stretch marks on her abdomen
Multiple bruises on her limbs
Frontal balding
Thinning of the axillary hair
Cafe au lait spots
Submit answer
I
Reference ranges v
Multiple bruises on her limbs
Frontal balding
Thinn ing of the axillary hair
Cafe au lait spots
Thinning of pubic and axillary hair is seen in females with

Addison's disease due to reduced production of testosterones
from the adrenal gland
Importance: 50
The correct answer is thinning of the axillary hair. The patient has failure
of the adrenal gland due to autoimmune attack. As well as deficiency of
glucocorticoids and mineralocorticoids, she will have lower levels of
androgens, which are usually produced in females by the zona
reticularis of the adrenal cortex. This leads to thinning of hair grown at
puberty, which is androgen dependent. The scalp hair is unaffected.
Stretch marks, skin thinning, easy bruising and poor wound healing are
found in Cushing's disease or in patients given longterm exogenous
steroids. Cafe au lait spots are seen in neurofibromatosis type I.
NICE CKS. Addison's disease.
Next question )
Addison's disease

Features
craving'
• crisis : collapse, shock, pyrexia
Primary causes
• tuberculosis
• metastases ( e.g. bronchial carcinoma)
• HIV
Secondary causes
* Primary Addison's is associated with hyperpigmentation whereas

Next question )
Q1
Which one of the following regarding the management of thyroid

problems during pregnancy is incorrect?
Maternal free thyroxine levels should be kept in the upper third of

the normal reference range when treating thyrotoxicosls
Increased levels of thyroxine-binding globulin are seen in

pregnancy
Block-and-replace is preferable in pregnancy compared to

antithyroid drug titration
Breast feeding is safe whilst on thyroxine
Untreated thyrotoxicosis increases the risk of premature labour
Submit answer
Reference ranges v
Increased levels of thyroxine-binding globulin are seen in pregnancy
Block-and-replace is preferable in pregnancy compared to

antithyroid drug titration
Breast feeding is safe whilst on thyroxine
Untreated thyrotoxicosis increases the risk of premature labour
[ ,. •• • Discuss (1) Improve ]
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Thyrotoxicosis,
Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart


Management
choice
following : 'Propylthiouracil is used in the first trimester of pregnancy
in place of carbimazole, as the latter drug may be associated with
carbimazole'
• maternal free thyroxine levels should be kept in the upper third of
thyroid problems
Hypothyroidism
Key points
pregnancy
Next question )
("',..., ,,... .................... ,...+,........ I

Q2
A 62-year-old man is investigated for hypertension and proximal

myopathy. On examination he is noted to have abdominal striae. Which
one of the following is most associated with ectopic ACTH secretion?
Carcinoid tumour
Cardiac myxoma
Squamous cell lung cancer
Adrenal carcinoma
Submit answer
Reference ranges v
Cardiac myxoma
Adrenal carcinoma
Small cell lung cancer accounts 50-75% of case of ectopic ACTH

Importance: 50
Adrenal carcinoma and cardiac myxoma are causes of ACTH

independent Cushing's syndrome
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Cushing's syndrome: causes
It should be noted that exogenous causes of Cushing's syndrome (e.g.

glucocorticoid therapy) are far more common than endogenous ones.
ACTH dependent causes

• Cushing's disease (80%): pituitary tumour secreting ACTH
producing adrenal hyperplasia
• ectopic ACTH production (5-10%): e.g. small cell lung cancer
ACTHindependentcauses
• iatrogenic: steroids
• adrenal adenoma (5-10%)
• adrenal carcinoma (rare)
• Carney complex: syndrome including cardiac myxoma
• micronodular adrenal dysplasia (very rare)
Pseudo-Cushing's
• mimics Cushing's
• often due to alcohol excess or severe depression
• causes false positive dexamethasone suppression test or 24 hr
urinary free cortisol
• insulin stress test may be used to differentiate
Next question )
Save mv notes
Q3
A 78-year-old nursing home resident is admitted to the acute medical

unit after being found collapsed in his room. A carer from the nursing
home is present and reports that he has had regular 'hypos' recently. On
admission he was drowsy and the blood glucose was 1.8 mmol/1.
Following intravenous dextrose the patient's condition significantly
improved.
His medication on admission is as follows:
Metformln 1g bd
Gliclazide 160mg od
Ploglitazone 45mg od
Aspirin 75mg od
Simvastatin 40mg on
What is the most appropriate initial action?
Stop metformin
Stop pioglltazone
Stop gliclazide
Make no changes to the medication
Stop all oral antidiabetic medications
Submit answer
Reference ranges v
His medication on admission is as follows:
Metformin 1g bd
Gliclazide 160mg od
Pioglitazone 45mg od
Aspirin 75mg od
Slmvastatin 40mg on
What is the most appropriate initial action?
rStop metformin
Stop pioglitazone
Stop gliclazide
Make no changes to the medication
Stop all oral antidiabetic medications
Neither metformin nor pioglitazone cause hypoglycaemia . The

gliclazide dose is therefore responsible and should be stopped whilst
deciding upon longer term changes to his medication.
a6 1f tl Discuss (5) Improve ]
Next question )
0 Q4
A 57-year-old woman is referred to urogynaecology with symptoms of

urge incontinence. A trial of bladder retraining is unsuccessful. It is
therefore decided to use a muscarinic antagonist.
Which one of the following medications is an example of a muscarinic

antagonist?
To!terodine
Teriparatide
Toremifene
Finasteride
Tamsulosin
Submit answer
Reference ranges v
I Tolterodine
Teriparatide
Toremifene
Finasteride
Tamsulosin
Other examples of muscarinic antagonists used in urinary incontinence

include oxybutynin and solifenacin. Examples of muscarinic
antagonists used in different conditions include ipratropium (chronic
obstructive pulmonary disease) and procyclidine (Parkinson's disease).
Tamsulosin is an alpha blocker.
•• If • Discuss Improve
Next question )
Urinary incontinence (UI) is a common problem, affecting around 4-5%

of the population. It is more common in elderly females.
Risk factors
• advancing age
• previous pregnancy and childbirth
• high body mass index
• hysterectomy
• family history
Classification
• overactive bladder (OAB)/urge incontinence: due to detrusor
overactivity
• stress incontinence: leaking small amount s when coughing or
laughing
• overflow incontinence: due to bladder outlet obstruction, e.g. due
• bladder diaries should be completed for a minimum of 3 days
initiate voluntary contraction of pelvic floor muscles ('Kegel'
exercises)
• urine dipstick and culture
Management depends on whether urge or stress UI is the predominant

• bladder retraining (lasts for a minimum of 6 weeks, the idea is to
• bladder stabilising drugs: antimuscarinics are first-line. NICE
recommend oxybutynin (immediate release), tolterodine
(immediate release) or darifenacin (once daily preparation).
older women'
• mirabegron (a beta-3 agonist) may be useful if there is concern
about anticholinergic side-effects in frail elderly patients

• pelvic floor muscle training: NICE recommend at least 8
contractions performed 3 times per day for a minimum of 3
months
QS
What causes increased sweating in patients with acromegaly?
Increased sodium content in sweat
Raised basal metabolic rate
Episodic hypoglycaemia
Low-grade chronic pyrexia
Sweat gland hypertrophy
Submit answer
Reference ranges v
I Sweat gland hypertrophy
Acromegaly: increased sweating is caused by sweat gland

hypertrophy
Importance: 50
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In acromegaly there is excess growth hormone secondary to a pituitary

Features
hypertrophy
• raised prolactin in 1/ 3 of cases - galactorrhoea
Complications
• hypertension
• diabetes (>10%)
• cardiomyopathy
Q6
A 40-year-old woman complains of feeling tired all the t ime and putting
on weight. On examination a diffuse, non-tender goitre is noted. Blood
tests are ordered:
TSH 15_ 1 mU/I
Free T4 7.1 pmol/I
ESR 14 mm/hr
Antl-TSH receptor stimulating antibodies Negative
Anti-thyroid peroxidase antibodies Positive
Pituitary failure
Primary atrophic hypothyroidism
Grave's disease
Submit answer
De Quervain's thyroiditi s
Grave's disease
Hashimoto's thyroiditis =hypothyroidism+ goitre+ anti-TPO

Importance: 50
This patient has Hashimoto's thyroiditis, as evidenced by the

hypothyroidism, goitre and anti-thyroid peroxidase antibodies. De
Quervain's thyroiditis typically causes a painful goitre and a raised ESR.
Around 90% of patients with Grave's disease have anti-TSH receptor
stimulating antibodies.
" •• tll Discuss (1) Improve ]
Next question )
Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is an

autoimmune disorder of the thyroid gland . It is typically associated with
1
hypothyroidism although there may be a transient thyrotoxicosis in the

acute phase. It is 1O times more common in women
Features
• features of hypothyroidism
• goitre: firm, non-tender
• anti-thyroid peroxidase and also anti-Tg antibodies
Hypothyroidism Hyperthyrodism
Hashimoto1s
thyroiditis Subacute thyroiditis
{ma) b€- Iii"'} b..c:! II, , .,to•Jt (de Quervain's) Graves' disease
pt,ase II iat,•) (lrutlal 01,,er ll}'pert rolCJ pnase •ouov,eo ~
longer h~potll)'rold pflase)

Amiodarone Toxic multinodular goitre
Riedel's thyroiditis
Postpartum thyroiditis
Iodine deficiency :lit-I ~ ... n, •.er: .,ro,d pl'la:.t! 'OllCnell b-y
longer fl)potnyrold prtas.e)
Lithium
C Passmedlcme corn
Q7
A 24-year-old woman is found to have a blood pressure of 170/100

mmHg during a routine medical check. She is well and clinica l
examination is unremarkable. Blood tests show:
Na+ 140 mmol/I
K+ 2.6 mmol/I
Bicarbonate 31 mmol/I
Urea 3.4 mmol/I
Creatinine 77 µmol/I
Which one of the following investigations is most likely to be

diagnostic?
Renal ultrasound
MR angiography
21-hydroxylase estimation
Submit answer
Renin :aldosterone ratio
MR angiography
21-hydroxylase estimation
A plasma aldosterone/renin ratio is the first-line investigation in

suspect ed primary hyperaldosteronism
Importance: 50
Conn's syndrome is the likely diagnosis - a renin:aldosterone ratio would

be an appropriate first-line investigation. A normal clinical examination
makes a diagnosis of Cushing's syndrome less likely
9' •• ,- Discuss (4) Improve
Next question )

Features
• hypertension
• hypokalaemia
• alkalosis
Investigations
aldosterone)
Management
spironolactone
Q8
A 60-year-old female, who is a known type 2 diabetic, presents to the GP

for a diabetes review. She is already on metformin and her GP decided
to start her on a sulphonylurea to help gain better control of her blood
sugar. What is the mechanism of action of this medication?
Closes calcium channels on the beta cells
Opens calcium channels on the beta cells
Inhibits sodium transport in the beta cells
Opens potassium-ATP channels on the beta cells
Closes potassium-ATP channels on the beta cells
Submit answer
Reference ranges v
l Closes potassium-ATP channels on the beta cell s
Sulfonylureas - bind to an ATP-dependent K+(KATP) channel on the

cell membrane of pancreatic beta cells
Importance: 50
Sulphonylureas work via mimicking the role of ATP on potassium-ATP

channels from the outside. They act to block these channels causing
membrane depolarisation and thus opening of voltage-gated calcium
channels. This process results in the stimulation of insulin release.
When used acutely they increase insulin secretion and decrease insulin
clearance in the liver. However, due to this stimulation of insulin
secretion they can cause hypoglycaemia, the main side effect, and this
can lead to the serious complication of neuroglycopenia.
This resulting lack of glucose supply to the brain can cause confusion
and possible coma. Treatment of this should be through oral glucose,
intramuscular glucagon or intravenous glucose.
If the tissue is exposed chronically to sulphonylureas there is no acute

increase in insulin release but a decrease in plasma glucose
concentration does remain . Chronic exposure to sulphonylureas does
also lead to down-regulation of their receptors.
[ ,. " • Discuss Improve ]
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.. I ,,.,,,,,, I J l '-'~UV'-' I I I lt-'I 'VY'-'
Next question )
Sulfonylureas

secretion and hence are only effective if functional B-cells are present.
On a molecular level they bind to an ATP-dependent K+(KAr P) channel

• weight gain

secretion
Sulfonylureas shou ld be avoided in breastfeeding and pregnancy.
Next question )
B I l!!J A ...
Q9
A 73-year-old man is seen in incontinence clinic by a speciality doctor.

He has a past medical history of urge incontinence. He has tried
oxybutynin in the past but did not find it helpful. He didn't tolerate
tolterodine either due to his longstanding constipation. The doctor
prescribes a 6- week course of mirabegron.
What is the mechanism of action of mirabegron?
Beta-2 agonist
Beta-1 agonist
Beta-3 agonist
Alpha-1 agonist
Alpha-1 antagonist
Submit answer
Reference ranges v
Beta-1 agonist
Beta-3 agonist
Alpha-1 agonist
Alpha-1 antagonist
Mirabegron is a beta-3 agonist

Importance: 50
Mirabegron is a beta-3 agonist used in the management of urge

incontinence if the other drugs such as oxybutynin fail to work or are
contraindicated.
Salbutamol is a beta-2 receptor agonist and causes bronchial smooth

muscle relaxation . Beta-2 receptors are predominantly found in the
lungs.
Beta-1 agonists, such as dobutamine, are used as inotropic agents in

congestive heart failure.
Doxazosin is an alpha-1 antagonist, used in the management of

hypertension.
Phenylephrine is an alpha-1 agonist. It acts as a vasoconstrictor and is

used as a nasal decongestant.
,6 'f • Discuss Improve ]
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Risk factors
• advancing age
• hysterectomy
• family history
Classification
• overactive bladder (OAB)/ urge incontinence: due to detrusor
overactivity
• stress incontinence: leaking small amounts when coughing or
laughing
exercises)
older women'

• pelvic floor muscle training : NICE recommend at least 8
months
Next question )
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Q10
A 20-year-old woman with a history of type 1 diabetes since the age of 8

comes to the Emergency department with nausea, vomiting, weight loss
and frequent episodes of hypoglycaemia. She has been treated with a
basal bolus regime of insulin since diagnosis and usually has very
stable diabetes control. On examination, her blood pressure is 105/70
mmHg with a postural drop of 15 mmHg. Her pulse is 74 beats per
minute and regular. Her body mass index is 21 kg/m 2 •
Investigations
Na+ 127 mmol/1
K+ 5.0 mmol/1
Urea 11.2 mmol/1
Glucose 4.8 mmol/ 1
TSH 10.2 IU/I
Free thyroxine 7 pmol/1
Which of the following is the most important intervention?
Fluid restriction
IV hydrocortisone
IV normal saline
Oral fludrocortisone
Oral thyroxine
IV hydrocortisone
IV normal saline
Oral fludrocortisone
Oral thyroxine
The hyponatraemia and potassium towards the upper end of the normal
range, coupled with hypoglycaemia, fit well with a diagnosis of
Addison's disease. Although features of hypothyroidism may co-exist
with hypoadrenalism, corticosteroid replacement is the most important
first step in therapy because commencing thyroxine may worsen any
adrenal crisis.
Fluid restriction is not appropriate given signs of volume depletion and

the likelihood of Addison's being the primary diagnosis. Although fluid
replacement with normal saline may be useful in relieving symptoms of
volume depletion, it is unlikely to be effective without commencing
hydrocortisone therapy. Oral fludrocortisone is added to hydrocortisone
in patients who are corticosteroid replete but still suffer from symptoms
of hyponatraemia or volume depletion.
16 11, tit Discuss (4) Improve
Next question )
Addison's disease

Features
craving'
• crisis: collapse, shock, pyrexia
Primary causes
• tuberculosis
• metastases (e.g. bronchial carcinoma)
• HIV
Secondary causes
*Primary Addison's is associated with hyperpigmentation whereas

Next question )
Q11
A 21-year-old with type 1 diabetes was admitted with abdominal pain

and vomiting. She had been having dysuria and urine dip showed ++
nitrites and ++ leucocytes. Her heart rate was 90 bpm and blood
pressure was 112/80 mmHg. Capillary glucose was 28 mmol/ I and
capillary ketones were 5.1 mmol/1. A venous gas was obt ained which
showed:
pH 7.25
Base excess -3.8
Lactate 2.9 mmol/1
Potassium 6.0 mmol/ 1
She was started on IV fluids and fixed-rate IV insulin. Her capillary

glucose and ketones had improved significantly after 24 hours of
treatment, however she gradually started to become confused, irritable
and was slurri ng her words . A repeat venous gas showed:
pH 7.32
Base excess -2.0
Lactate 2.3 mmol/1
Potassium 3.1 mmol/1

Lactate 2.3 mmol/1
Potassium 3.1 mmol/1
What is the most likely cause of her new neurological symptoms?
Stroke
Encephalopathy
Cerebral oedema
Sepsis
Hypokalaemia
I
Submit answer
Reference ranges v
Cerebral oedema
Sepsis
Hypokalaemia
Cerebral oedema is an important complication of fluid

resuscitation in OKA, especially in young patients
Importance: 50
Children/young adults are particularly vulnerable to cerebral oedema

following fluid resuscitation in OKA and often need 1:1 nursing to
monitor neuro-observations, headache, irritability, visua l disturbance,
focal neurology etc.
It usually occurs 4-12 hours following commencement of treatment but

can be present at any time.
If any suspicion, request a CT head and call senior immediately.
••
11
Next question >
Diabetic ketoacidosis (OKA) may be a complication existing type 1

2 diabetes mellitus may also develop OKA.
Whilst OKA remains a serious condition mortality rates have decreased

from 8% to under 1% in the past 20 years.
Pathophysiology
• OKA is caused by uncontrolled lipolysis (not proteolysis) which
The most common precipitating factors of OKA are infection, missed

Features
• abdominal pain
Diagnostic criteria


• glucose > 13.8 • glucose > 11 mmol/I or known
mmol/I diabetes mellitus
• pH< 7.30 • pH < 7.3
• serum bicarbonate • bicarbonate< 15 mmol/I
<18 mmol/ I • ketones > 3 mmol/ I or urine
• anion gap> 10 ketones ++ on dipstick
• ketonaemia
Management
regime below.
unit/kg/ hour. Once blood glucose is < 15 mmol/ I an infusion of 5%
unit/ kg/ hour. Once blood glucose is< 15 mmol/ I an infusion of 5%
should be stopped

Fluid Volume
0. 9% sodium chloride 1 L 1000ml over 1 st hour

chloride hours

chloride hours

chloride hours

chloride hours

chloride hours
18-25 years) as they are at greater risk of cerebral oedema.

hours (mmol/L) of infusion solution
Over 5.5 Nil
3.5-5.5 40

potassium needs to be given

• gastric stasis
• thromboembolism
• arrhythmias secondary to hyperkalaemia/latrogenic hypokalaemia
* children/young adults are particularly vulnerable to cerebral oedema

following fluid resuscitation in DKA and often need 1:1 nursing to
Next question )
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Q12
A 45-year-old female is admitted to the Emergency Department with

abdominal pain associated with vomiting. She has a past medical
history of hypothyroidism and takes thyroxine. On examination she is
pyrexial at 37.6°C. Pulse is 11 O bpm with a blood pressure of 100/64
mmHg. Blood results show the following :
Na+ 131 mmol/1
K+ 4.9 mmol/1
Urea 8.1 mmol/1
Creatinine 11 O µmol/1
Glucose 3.3 mmol/1
What treatment should be given first?
Ceftriaxone + benzylpenicillin
Glucagon
Propranolol
Triiodothyronine
Hydrocortisone
Submit answer
Na+ 131 rnmol/1
K+ 4.9 mmol/1
Urea 8.1 mmol/1
Creat lnlne 11 O µmol/1
Glucose 3 .3 mmol/ 1
What treatment should be given first?
~ eftriaxone + benzylpenicillin
Glucagon
Propranolol
Triiodothyronine
I Hydrocortisone
This is a typical history of Addison's. Patients may have a history of

other autoimmune conditions such as thyroid disorders. Steroids
should be given as soon as possible
[ ,6 If tt Discuss (1 1) Improve ]
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Q13
Which one of the following drugs is least likely to cause

gynaecomastia?
Sp ironolactone
Sodium va lproate
Digoxin
Cimetidine
Anabolic steroids
Submit answer
Reference ranges v
Sodium valproate
Digoxin
Cimetidine
Anabolic steroids
Whilst sodium valproate may rarely causes gynaecomastia it is much

more common after taking the other listed drugs.
[ ,, If • Discuss (2) Improve ]
Next question )
Gynaecomastia

• liver disease
• hyperthyroidism
• haemodialysis

• cimetidine
• digoxin
• cannabis
• finasteride

• tricyclics
• isoniazid
• heroin
• busulfan
• methyldopa
Q14
A 34-year-old woman is referred to the endocrinology clinic with

symptoms of anxiety and significant weight loss. She reports feeling
unusually hot all the time. Blood tests are as follows:
TSH 0.03 (0.27 - 4.20 mU/1)
Free T4 37 (10.0 - 23.0 pmol/1)
The endocrinologist arranges a nuclear scintigraphy scan which reveals

patchy uptake.
Grave's disease
Hashimoto's disease
Iodine deficiency
Solitary adenoma
Submit answer
Ref erence ranaes v

1vrn1 ,e ae11c1e1 ,cy
Solitary adenoma
I Toxic multinodular goitre

-------~
In toxic multinodular goitre, nuclear scintigraphy reveals patchy

uptake
Importance: 50
The combination of hyperthyroid symptoms, blood results, and patchy

uptake on nuclear scintigraphy point towards a diagnosis of toxic
multinodular goitre. This is a common cause of hyperthyroidism in
which there is excess production of thyroid hormones from functionally
autonomous thyroid nodules.
In Graves disease, scintigraphy would show diffuse enlargement of both

thyroid lobes, with uniform uptake throughout. Grave's is an
autoimmune disorder and the most common cause of hyperthyroidism.
Hashimoto's disease typically presents with symptoms of

hypothyroidism as opposed to hyperthyroidism. Hashimoto's is an
autoimmune condition.
Iodine deficiency leads to hypothyroidism, as iodine is used to make

thyroid hormones. This is uncommon in the developed world but may
be seen in developing countries.
A solitary adenoma would present similarly to toxic multinodular goitre,

but you would expect nuclear scintigraphy to show a small focus of
uptake.
9' •t .- Discuss Improve
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Next question )
Toxic multinodular goitre describes a thyroid gland that contains a

number of autonomously functioning thyroid nodules resulting in
hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
The treatment of choice is radioiodine therapy.
Next question )
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Q15
A middle-aged man with type 2 diabetes mellitus is reviewed. Despite

weight loss, metformin and gliclazide his HbA 1c is 68 mmol/mol
(8.4%). The patient agrees to start insulin therapy. According to NICE
guidelines which type of insulin should be tried initially?
Basal bolus regime
lsophane (NPH insulin)
Biphasic insulin
Glargine
Detemir
Submit answer
Reference ranges v
lsophane (NPH insulin)
Biphasic insulin
Glargine
Detemir
From NICE Clinical Knowledge Summaries:
The National Institute for Health and Care Excellence (NICE)

recommends that in adults with type 2 diabetes:
• Neutral Protamine Hagedorn (NPH) insulin [also known as
isophane insulin] (injected once or twice daily according to
need) should be offered.
• NPH plus a short-acting insulin should be considered
(particularly if the person's HbA1c is 75 mmol/mol [9.0%] or
higher). This may be administered either separately or as a
pre-mixed (biphasic) human insulin preparation.
• Insulin detemir or insulin glargine should be considered as an
alternative to NPH insulin if:
• - The person needs assistance from a carer or healthcare
professional to inject insulin and the use of insulin detemir or
insulin glargine would reduce the frequency of injections
from twice to once dailY, or
• - The person's lifestyle is restricted by recurrent
symptomatic hypoglycaemic episodes, or
• _, The person would otherwise need twice-daily NPH insulin
injections in combination with oral antidiabetic drugs.
Q16 Jr:::J
One of your patients is diagnosed with having the metabolic syndrome.

Which one of the following is associated with this condition?
Endometriosis
Hypothyroidism
Asymptomatic rise in amylase levels
Elevated albumin levels
Raised uric acid levels
Submit answer
Reference ranges v
l Raised uric acid levels
Next question )
Metabolic syndrome
Unfortunately there are a number of competing definitions of the

metabolic syndrome around at the present time. It is thought that the
key pathophysiological factor is insulin resistance.
SIGN recommend using criteria similar to those from the American

Heart Association. The similarity of the International Diabetes
Federation criteria should be noted. For a diagnosis of metabolic
syndrome at least 3 of the following should be identified:
• elevated waist circumference: men > 102 cm, women > 88 cm
• elevated triglycerides: > 1.7 mmol/ L
• reduced HDL: < 1.03 mmol/ L in males and< 1.29 mmol/L in
females
• raised blood pressure: > 130/85 mmHg, or active treatment of
hypertension
• raised fasting plasma glucose > 5.6 mmol/L, or previously
The International Diabetes Federation produced a consensus set of

diagnostic criteria in 2005, which are now widely in use. These require
the presence of central obesity (defined as waist circumference> 94cm
for Europid men and > 80cm for Europid women, with ethnicity specific
values for other groups) plus any two of the following four factors:
• raised triglycerides level: > 1.7 mmol/ L, or specific treatment for
this lipid abnormality
• reduced HDL cholesterol : < 1.03 mmol/L in males and< 1.29
• reduced HDL cholesterol: < 1.03 mmo l/L in male s and < 1 .29
mmo l/L in females, or speci fic treatm ent for this lipid abno rmali ty
• raised blood pressure: > 130/ 85 mm Hg, or active treatm ent of
hypertension
• raised fastin g plasm a gluco se> 5.6 mmo l/ L, or previously
In 1999 the World Health Organization produced diagn ostic criter ia

which required the presence of diabetes mellitus, impaired gluco se
tolerance, impaired fastin g gluco se or insuli n resistance, AND two of
the follow ing:
• blood pressure: > 140/ 90 mmH g
• dyslipidaemia: triglycerides: > 1.695 mmo l/ L and/ or high-dens ity
lipoprotein cholesterol (HDL-C) < 0. 9 mmo l/ L (male), < 1.0 mmo l/L
(female)
• central obesity: waist :hip ratio > 0.90 (male), > 0.85 (fema le),
and/ or body mass index > 30 kg/m 2
• microalbuminuria : urinary albumin excretion ratio > 20 mg/ min or
albumin:creatinine ratio > 30 mg/ g
Other associated features include:

• raised uric acid levels
• non-alcoholic fatty liver disease
Next ques tion )
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CamScanner ~ ·. .;~ .__;.,..a..:,

Q17
A 62-year-old HGV driver is reviewed. He was diagnosed last year with

type 2 diabetes mellitus. Following weight loss and metformin his
HbA 1c has decreased from 74 mmol/mol (8.9%) to 68 mmol/ mol
(8.4%). What is the most suitable next step in management?
Add exenatide
Make no changes to management
Add gliclazide
Stop metformin for a period to ensure hypoglycaemic awareness

is not lost
Add pioglitazone
Submit answer
Reference ranges v
Make no changes to management
Add gliclazide
Stop metformin for a period to ensure hypoglycaemic awareness is

not lost
l Add pioglitazone
Pioglitazone is the best option here as it would not put him at risk of
hypoglycaemia, which obviously could be dangerous given his job. The
NICE guidelines would also support the use of a DPP-4 inhibitor (e.g.
sitagliptin or vildagliptin) in this situation.
[ ,t •t tt Discuss (8) Improve ]
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Q18
A 49-year-old woman is investigated for thyrotoxicosis. On examination

she is noted to have a goitre conta ining multiple irregular nodules.
Nuclear scintigraphy with technetium 99m reveals patchy uptake. What
is the treatment of choice?
Corticosteroids
Radioiodine
Block-and-replace regime
Surgery
Anti-thyroid drug titration regime
Submit answer
Reference ranges v
Radioiodine
Block-and-replace regime
surgery
Anti-thyroid drug titration regime
Next question >
Toxic multinodular goitre describes a thyroid gland that contains a

number of autonomously functioning thyroid nodules resulting in
hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
The treatment of choice is radioiodine therapy.
Next question )
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Q19
A 54-year-old man has a routine medical for work. He is asymptomatic

and clinical examination is unremarkable. Which of the following results
establishes a diagnosis of impaired fasting glucose?
Fasting glucose 7.1 mmol/L on one occasion
Fasting glucose 6.8 mmol/L on two occasions
Glycosuria ++
75g oral glucose tolerance test 2 hour value of 8.4 mmol/L
HbA 1 c of 6.7%
Submit answer
Reference ranges v
Fasting glucose 6.8 mmol/L on two occasions
Glycosuria ++
75g oral glucose tolerance test 2 hour value of 8.4 mmol/ L
HbA1 c of 6.7%
A 75g oral glucose tolerance test 2 hour value of 8.4 mmol/L would
imply impaired glucose tolerance rather than impaired fasting glucose
Next question )


• fasting glucose greater than or equal to 7.0 mmol/1
• random glucose greater than or equal to 11.1 mmol/1 (or after 75g

Fasting glucose: -e:: 60mmol1 ~= 7 0 mmol/1
,.,ediabete:s
NonNI ~ I C c--«il Dsabetas---
f-,q:)Alt 114~-H ll"fflOl'ffl()j 18 c-e .I l
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"A •r,,g gu:ow 6 1~ P mmo'l
In 20 I I WHO released supplement ary guidance on the use of AbA Icon
• a HbA 1 c of greater than or equal to 48 mmol/mol (6.5%) is
• a HbAlc value of less than 48 mmoi/mol (6.5%) does not exclude
diabetes)
Conditions where HbA 1 c may not be used for diagnosis:

• children
• HIV
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmoi/1

less than 7.0 mmoi/1and OGTT 2-hour value greater than or equal to 7.8
mmol/1 but less than 11 .1 mmol/1
mmoi/1 but above 7.8 mmoi/1 indicates that the person doesn't
Q20
A 53-year-old female with a history of primary atrophic hypothyroidism

is assessed two months following a change in her dose of
levothyroxine. Which one of the following best describes what the TSH
should id eally be?
Between 0.5 to 1.0 mU/ I
Submit answer
Reference ranges v
Between 0.5 to 2.5 mU/ 1
Between 2.5 to 4 .5 mU/ 1
A TSH value between 0.5 to 2.5 mU/ 1is now considered preferable.
Dosage changes should of course also take account of symptoms
[ "' I •• t9 Discuss (2) Improve ]
Next question )
Key points
TSH value 0.5-2.5 mU/ I it is now thought preferable to aim for a
TSH in this range

Interactions
apart
Q1
A 45-year-old female is reviewed in the medical cli nic with a two month
history of lethargy. Blood tests reveal the following:
Na+ 129 mmol/I
K+ 5.1 mmol/1
Urea 5.3 mmol/1
Tot al T4 66 nmol/I
Which one of the following investigations is most likely t o reveal the

diagnosis?
Serum glucose
TSH
Free T4
Submit answer
Reference ranges v
TSH
Free T4
The short synacthen test is the best test to diagnose Addison's

disease
Importance: 50
Hyponatraemia and a high potassium in a patient with lethargy is highly

suggestive of Addison's disease. The thyroxine level is slightly low and
she may indeed have co-existing hypothyroidism but this would not
explain the high potassium
Many labs have an upper reference range for potassium of 5.5 mmol/1,
but in the context of the other results hypoadrenalism shou ld be
suspected
•• •• - Discuss (6) Improve
Next question)
Next question )

is an ACTH stimulation test (short Synacthen test). Plasma cortisol is
measured before and 30 minutes after giving Synacthen 250ug IM.
demonstrated.

• > 500 nmol/I makes Addison's very unlikely
• < 100 nmol/I is definitely abnormal
• 100-500 nmol/I should prompt a ACTH stimulation test to be
performed

• hyperkalaemia
• hyponatraemia
• hypoglycaemia
Next question )
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Save my notes
A 54-year-old-woman with known ovarian cancer presents with
confusion. She has become progressively confused over the last few
days, and prior to that, she had started to become constipated. Her
family describes poor oral intake of fluids and poor urinary output as
well. On further discussion with the family, they mention that she was
seen in oncology clinic two weeks ago with results of a bone scan
which they had been told was normal.
On examination, she appears dehydrated.
Hb 147 g/1
Platelets 321*109/1
WBC 7.8*109/1
Na+ 142 mmol/ 1
K+ 4.7 mmol/ 1
Urea 4.6 mmol/ 1
Corrected calcium 3.2 mmol/1
Parathyroid hormone Pending
What is the most likely cause of her elevated calcium?
Osteolytic hypercalcaemia
Calcitriol-mediated hypercalcaemia
Ectopic PTH secretion
Parathyroid-hormone-related peptide release
Calcitriol-mediated hypercalcaemia
Ectopic PTH secretion
Parathyroid-hormone-related peptide release
The correct answer is parathyroid-hormone-related peptide release.

Whilst this is classically described as secondary to squamous cell lung
cancer, it can occur in many malignancies.The two most common
causes of hypercalcaemia are malignancy and primary
hyperparathyroidism . In malignancy, roughly 80% of cases are due to
parathyroid-hormone-related peptide release. The vast majority of
remaining cases are due to osteolysis, and some due to calcitriol-
mediated hypercalcaemia and ectopic PTH secretion. Primary
hyperparathyroidism is another common cause but is not as likely as
malignant hypercalcaemia given the known diagnosis of ovarian cancer.
Source:
'Hypercalcaemia of Malignancy.' BMJ Best Practice. 14 June 2016.
[ ,6 •t - Discuss (3) Improve ]
Next question >

ex ques 10n


• sarcoidosis*
• acromegaly
• thyrotoxicosis
• dehydration
• Paget's disease of the bone**


Next question )
B I /!j A ..,. T I""

Q1
A 66-year-old lady with a long hist ory of poorly control led type-2
diabetes is started on a new medication. She is told it works by
increasing urinary glucose excretion and the doctor says it is an SGLT-2
inhibitor.
Which of the fo llowing medications is in t his drug class?
Tolbutamide
Dapagliflozin
Exenatide
Linagliptin
Pioglitazone
Submit answer
Reference ranges v
Dapagliflozin
Exenatide
Linagl iptin
Pioglitazone
Gliflozins - SGLT2 inhibitors

lmportahce: 50
Gliflozins are SGLT2 inhibitors.
Tolbutamide is a sulfonylurea.
Exenatide is a GLP-1 receptor agonist.
Linagliptin is a DPP-4 inhibitor.
Pioglitazone is a thiazolidinedione.
Next question)
Q2
Which one of the following hormones is under continuous inhibition?
Growth hormone
Prolactin
Gonadotropin releasing hormone
Thyroid releasing hormone
Adrenocorticotrophic hormone
Submit answer
Reference ranges v
Prolactin
Gonadotropin releasing hormone
Thyroid releasing hormone
Adrenocorticotrophic hormone
Prolactin - under continuous inhibition

Importance: 50
Prolactin is unique amongst the pituitary hormones in being tonically

inhibited by the hypothalamus
[ ,, •• • Discuss (1) Improve ]
Next question )

Next ques tion )
se being
Prolactin is secreted by the ante rior pitui tary gland with relea
acts as
contr olled by a wide variety of phys iolog ical facto rs. Dopa mine
mine
the prim ary prola ctin releasing inhib itory facto r and henc e dopa
torrh oea.
agon ists such as brom ocrip tine may be used to contr ol galac
to the
It is impo rtant to diffe renti ate the caus es of galac torrh oea (due
astia
actio ns of prola ctin on brea st tissu e) from thos e of gyna ecom
Features of excess prola ctin

• men: impotence, loss of libido, galac torrh oea
• women: amenorrhoea, galac torrh oea
Causes of raised prola ctin

• prola ctino ma
• pregnancy
• oestr ogen s
• acromegaly: 1/3 of patie nts
• polyc ystic ovarian synd rome
one
• prim ary hypo thyro idism (due to thyro troph in releasing horm
(TRH) stimu lating prola ctin release)
Drug caus es of raised prola ctin

• meto clopr amide, dom perid one
• phenothiazines
• halop erido l
• very rare: SSRl s, opio ids
Next ques tion )

Q3
Which one of the following features is least associated with primary

hyperparathyroidism?
Depression
Polydipsia
Sensory loss
Peptic ulceration
Hypertension
Submit answer
Reference ranges v
Polydipsia
Sensory loss
Peptic ulceration
Hypertension
[ ,6 I •• tll Discuss (2) Improve
Next question)
Q4
You have been asked to review a 52-year-old woman in the emergency

department with dyspnoea accompanied by nausea and vomiting. She
tells you that she initially attributed this to a flu-like illness but as she
found herself becoming increasingly short of breath she was taken to
hospital by her concerned husband. Her past medical history is
sign ifi cant for type 2 diabetes mellitus, hypertension and obes ity. Her
current medications include metformin 1gram bd, canagliflozin 100mg
od, ramipril 10mg od and amlodipine 5mg od. On examination she has a
respiratory rate of 25 breaths/min, blood pressure 130/ 67 mm Hg, pulse
105 bpm and oxygen saturation of 98% on room air. The only finding
you elicit on physical examination is mild tenderness in the epigastric
area. Her ECG shows a sinus tachycardia. Routine blood results are
shown below:
132 22
Hb 167 g/1 Na+ Bilirubin pH 7.14
mmol/1 µmol/1
410 * K+ 5.5
Platelets ALP 100 u/1 Pa02 12 KPa
109 / 1 mmol/1
11 .2 * 10.4
WBC Urea ALT 55 u/1 PaC02 1.9 KPa
109 / 1 mmol/1
10.0 * 111
Neuts Creatinine yGT 23 u/1 HC03- 11 µmol/1
109 / 1 µmol/1
1.1 * 3.0
Lymphs Amylase 321 U/ 1 A lbumin 33 g/1 Lactat e
109 / 1 mmol/1
0.1 * c1-
101 Ketones
Eosin Urine Glucose 11 mmol/L
109 / 1 mmol/1 3+
Eosin
109 / 1
er mmol/ 1
Urine
3+
Glucose 11 mmo!/ L
Small bowel obstruction
Metformin induced lactic acidosis
Starvation ketosis
Euglycaemic diabetic ketoacidosis
Pancreatitis
Submit answer
Reference ranges v
Metformin induced lactic acidosis
Starvation ketosis
Euglycaemic diabetic ketoacidosis
Pancreatitis
This lady has euglycaemic diabetic ketoacidosis (EuDKA) secondary to

her sodium-glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin.
EuDKA is an important to recognise side effect of this novel class of
oral hypoglycaemic agents and should be thought of in any patient with
an unexplained raised anion gap acidosis and normal blood sugar level
who is on one of these medications.
Exactly how these agents cause EuDKA has yet to be determined.

However, it is hypothesised that as these agents lower blood sugar
levels by increasing the excretion of glucose the resu lting reduction in
plasma glucose results in reduced insulin secretion from pancreatic
beta-cells and these patients entering a state of relative insulin
deficiency. This leads to a lowering of the antilipolytic activity of insulin,
and the consequent stimulation of the production of free fatty acids,
which are then converted to ketone bodies by beta-oxidation in the liver.
Moreover, insulin stimulates the activity of acetyl-CoA carboxylase,
which produces malonyl-CoA, a potent inhibitor of carnitine
palmitoyltransferase (CPT-1). Given that CPT-1promotes the transport of
fatty acids into mitochondria and hence increases the rate of beta-
oxidation, the decrease in the circulating level of insulin promotes the
production of ketone bodies through activation of CPT-1.
8
"' f • Discuss (8) Improve
Next question )
QS
A 45-year-old who is currently being investigated for lethargy and

reduced libido presets for follow-up. He initially presented after
requesting a testosterone blood test due to his reduced sexual drive.
This was reported as follows:
Testosterone 5.4 nmol/l (>9.0)
Subsequent blood tests show the following:
Prolactin 450 mu (< 400)
Cortisol (8am) 120 nmol/L (130-690)
FSH 0.8 IU/ L (1-8)
Addison's disease
Testicular cancer with brain metastases
Non-functioning pituitary adenoma
Prolactinoma
Craniopharyngioma
Submit answer
Reference ranges v
Testicular cancer with brain metastases
Non-functioning pituitary adenoma
Prolactinoma
Craniopharyngioma
Non-functioning pituitary tumours present with hypopituitarism

and pressure effects
Importance: 50
Whilst the prolactin level is slightly raised this can be caused by the
pressure effects of the tumour preventing dopamine (which inhibits
prolactin release) from reaching the normal prolactin-producing cells.
Much higher levels would be expected with a prolactinoma.
,6 ,. tt Discuss (7) Improve ]
Next question )
Pituitary adenoma
A pituitary adenoma is a benign tumour of the pituitary gland. They are

common (10% of all people1 ) but in most cases wi ll never be found
(asymptomatic) or are found as an incidental finding . They account for
around 10% of adult brain tumours2 .
Pituitary adenomas can be classified according to:

• size (a microadenoma is <1 cm and a macroadenoma is >1 cm)
• hormonal status (a secretary/functioning adenoma produces and
excess of a particular hormone and a non-secretary/functioning
adenoma does not produce a hormone to excess)
Cam Sc onner ...,, ',&~ .G. ~ I

Prolactinomas are the most common type and they produce an excess
of prolactin. After prolactinomas, non-secreting adenomas are the next
most common, then GH secreting and then ACTH secreting adenomas.
Pituitary adenomas typically cause symptoms by:

• excess of a hormone (e.g. Cushing's disease due to excess ACTH,
acromegaly due to excess GH or amenorrhea and galactorrhea
due to excess prolactin)
• depletion of a hormone(s) (due to compression of the normal
functioning pituitary gland)
o non-functioning tumours, therefore, present with generalised
hypopituitarism
• stretching of the dura within/ around pituitary fossa (causing
headaches)
• compression of the optic chiasm (causing a bitemporal
hemianopia due to crossing nasal fibers)
Alternatively, pituitary adenomas, particularly microadenomas, can be

an incidental finding on neuroimaging and therefore called a 'pituitary
incidentaloma'.
Investigation requires:
• a pituitary blood profile (including: GH, prolactin, ACTH, FH, LSH
and TFTs)
• formal visual field testing
• MRI brain with contrast
Differential diagnoses include:

• pituitary hyperplasia
• craniopharyngioma
• meningioma
• brain metastases
• lymphoma
• hypophysitis
• vascular malformation (e.g. aneurysm)
Treatment may include a combination of:
• hormonal therapy (e.g. bromocriptine is the first line treatment for
prolactinomas)
• surgery (e.g. transsphenoidal transnasal hypophysectomy)
o e.g. if progression in size
• radiotherapy
Next question )
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~
=-...,.
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Q Google search on "Pituitary adenoma"
Links
Patient.info
Pituitary tumours review

0 Q6
A 72-year-old woman presents with polyuria and polydipsia.

Investigations reveal the following:
Fasting glucose 4.5 mmol/1
Calcium 2.88 mmol/1
Phosphate 0.75 mmol/1
Parathyroid hormone 6 pmol/L (normal range= 0.8 - 8.5)
What is the most likely underlying diagnosis?
Myeloma
Sarcoidosis
Vitamin D excess
Osteomalacia
Submit answer
Reference ranges v
Sarcoidosis
Vitamin D excess
Osteomalacia
The PTH level in primary hyperparathyroidism may be normal

Importance: 50
Despite a raised calcium level the parathyroid hormone level is

inappropriately normal. This points towards a diagnosis of primary
hyperparathyroidism and the other causes (such as myeloma) would
lead to a suppression of parathyroid hormone
,6 'f - Discuss (10) Improve ]
Next question)
Q7
A 85-year-old male presents to clinic for a review of his overactive

bladder. Non-pharmacologic treatments have so far failed to improve
his symptoms. Which of the following pharmacotherapies represents
the most appropriate initial management step?
Finasteride
Desmopressin
Tamsulosin
Mirabegron
Tolterodine
Submit answer
Reference ranges v
ITolterodine
NICE (Feb 2015) outlines treatment steps for the management of

overactive bladder symptoms in men.
If non-pharmacologic measures fail, an anticholinergic agent is first

line. In older men, tolterodine is preferred to oxybutynin as the latter has
a greater risk of causing confusion.
If anticholinergics fail or are contraindicated, mirabegron may be

trialled . Its mechanism of action is via beta-adrenoreceptor-mediated
relaxation of the bladder wall.
Tamsulosin is an alpha-blocker and indicated if the patient if has

obstructive symptoms, rather than symptoms of overactive bladder.
Finasteride is a 5-alpha reductase inhibitor and indicated if the patient

has obstructive symptoms and an enlarged prostate with a high risk of
progression.
Desmopressin is a synthetic vasopressin analogue that acts in the

collecting duct of the nephron. It is sometimes used off-label for
nocturnal urinary incontinence.
[ ,6 'f • Discuss {8) Improve ]
Next question )
-
Risk factors
• advancing age
• hysterectomy
• family history
Classification
• overactive bladder (OAB)/urge incontinence: due to detrusor
overactivity
• stress incontinence: leaking small amounts when coughing or
laughing
exercises)
older women'

• pelvic floor muscle training : NICE recommend at least 8
months
Next question)
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·- 2= =
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- .. T I .... EEEI .... ~ c-::,
-
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-
Q8
A 55-year-old man with type 2 diabetes mellitus has his yearly health
check-up at his GP surgery. His HbA1c is 86mmol/L and his GP is
considering adding empagliflozin to help manage his diabetes.
HbA1c (mmol/L) Interpretation
<42 Normal Glycaemic Control
42-47 Impaired Glucose Tolerance
>48 Diabetes Mellitus
86 Patient's Result
What is the mechanism of action of this medication?
Blocks potassium channels on f3 islet cells in the pancreas
Inhibition of the sodium-glucose transporter in the kidney
Inhibition of dipeptidyl peptidase 4
Inhibition of a glucosidase in the small intestine
Stimulation of peroxisome proliferator-activated receptor
Submit answer
Inhibition of the sodium-glucose transporter in the kidney
Inhibition of dipeptidyl peptidase 4
Inhibition of a glucosidase in the small intestine
Stimulation of peroxisome proliferator-activated receptor

Importance: 50
Empagliflozin is an SGLT-2 (sodium-glucose transport protein 2)

inhibitor. These act in the proximal convoluted tubule of nephrons to
inhibit glucose re-absorption back into the circulation by blocking SGLT-
2 channels.
Sulphonylureas act via increasing insulin secretion from f3 islet cells in

the pancreas. They do this via blockage of potassium channels, which
causes islet cell depolarisation and release of insulin.
Inhibition of the enzyme DPP-4 (dipeptidyl peptidase 4) prevents the

break down of GLP-1 (glucagon-like peptide), which in turn suppresses
glucagon release and increases insulin release. Sitagliptin is an
example of this class of drug.
Acarbose inhibits a glucosidase and other enzymes in the small

intestine, preventing the breakdown of complex carbohydrates into
glucose. As a result, less glucose is made available for absorption into
the bloodstream.
Thiazolidinediones reduce insulin resistance in the peripheral tissues

and decrease gluconeogenesis in the liver. They achieve this by
stimulation of PPAR-y (peroxisome proliferator-activated receptor-
gamma) which modulates the transcription of genes involved in
glucose metabolism.
Q9
A S6-year-old Muslim man with a history of type 2 diabetes asks for

advice. He is due to start fasting for Ramadan soon and is unsure what
he should do with regards to his diabetes medications. He currently
takes metformin SOOmg tds . What is the most appropriate advice?
Switch to subcutaneous biphasic insulin for the duration of

Ramadan
SOO mg at the predawn meal + 1000 mg at the sunset meal
No change to the metformin dose
1000 mg at the predawn meal + SOO mg at the sunset meal
Stop metformin for the duration of Ramadan
Submit answer
Reference ranges v
500 mg at the predawn meal + 1000 mg at the sunset meal
No change to the metformin dose
1000 mg at the predawn meal + 500 mg at the sunset meal
Stop metformin for the duration of Ramadan
During Ramadan, one-third of the normal metformin dose should

be taken before sunrise and two-thirds should be taken after
sunset
Importance: 50
Please see the Diabetes Care link for more details.
[" •• tit Discuss (4) Improve ]
Next question )
Diabetes mellitus: Ramadan
We know that type 2 diabetes mellitus is more common in people of

Asian ethnicity and a significant proportion of those patients in the UK
will be Muslim. The BMJ published an excellent and comprehensive
review of this issue in 201 O1 .
It is important that we can give appropriate advice to Muslim patients to

allow them safely observe their fast. This is particularly important from
2014 as Ramadan is due to fall in the long days of the summer months
for several years henceforth.
Clearly it is a personal decision whether a patient decides to fast. It may

however be worthwhile exploring the fact that people with chron ic
conditions are exempt from fasting or may be able to delay fasting to
the shorter days of the winter months. It is however known that many
Muslim patients with diabetes do not class themselves as having a
chronic/serious condition which should exempt them from fasting.
Around 79% of Muslim patients with type 2 diabetes mellitus fast
Ramadan2 .There is an excellent patient information leaflet from
Diabetes UK and the Muslim Council of Britain which explores these
options in more detail.
If a patient with type 2 diabetes mellitus does decide to fast

• they should try and and eat a meal containing long-acting
carbohydrates prior to sunrise (Suhoor)
• patients should be given a blood glucose monitor to allow them to
check their glucose levels, particularly if they feel unwell
• for patients taking metformin the expert consensus is that the
dose should be split one-third before sunrise (Suhoor) and two-
thirds after sunset (lftar)
• expert consensus also recommends switching once-daily
sulfonylureas to after sunset. For patients taking twice-daily
preparations such as gliclazide it is recommended that a larger
proportion of the dose is taken after after sunset
• no adjustment is needed for patients taking pioglitazone
Q10
An elderly male of no fixed abode with a history of alcohol dependency

and chron ic liver disease is taken to t he Emergency Department with
reduced consciousness (GCS 5) and a blood glucose of 1.3 mmol/ L.
What is the correct management of his hypoglycaemia?
IM Glucagon STAT
Lucozade
100ml IV Normal Saline
100ml IV Dextrose 5%
100ml IV Glucose 20%
Submit answer
Reference ranges v
Lucoza de
100ml IV Normal Saline
100ml IV Dextros e 5%
I 100ml IV Glucose 20%
Hypogly caemia in patients with alcohol ic liver disease does not

respond to glucago n
Importance: 50
Patients with alcohol ic liver disease have depleted glycogen stores,

therefore, treatme nt with glucago n does not improve blood glucose .
It is not safe to use the oral route when the patient is GCS 5, therefore,
adminis tering Lucozade is not appropriate.
Normal saline does not correct hypoglycaemia .
5% dextros e is a mainten ance flu id and not appropr iate for acute
treatme nt of hypogly caemia .
Therefore, the correct answer is 100ml IV Glucose 20%.
[ ,6 ,. '9 Discuss (6) Improve ]
Next questio n )
Next question )
Hypoglycaemia
Causes
• liver failure
• alcohol


Next question )
B I A .... ·- 21-.: - - ....

T I""
1
Q11
A 53 year man presents as his wife has noticed a change in his

appearance. He has also noticed his hands seem larger. On
examination blood pressure is 170/94 and he is noted to have
bitemporal hemianopia. What is the most appropriate first-line
treatment?
Octreotide
External irradiation
Pegvisomant
Trans-sphenoidal surgery
Bromocriptine
Submit answer
Reference ranges v
External irradiation
Pegvisomant
Trans-sphenoidal surgery
Bromocriptine
Trans-sphenoidal surgery is the treatment of choice in acromegaly.

There is no significant evidence base supporting the use of pre-
operative octreotide
,6 ,. tit Discuss (9) Improve ]
Next question )
a _ __ _ __ _ _ _ I
•
Next question )

Dopamine agonists
• may be used as an adjunct to surgery
Pegvisomant
• once daily s/ c administration
mass effect

Next question )
Q12
A 56-year-old female is admitted to ITU with a severe pneumonia.

Thyroid function tests are most likely to show:
TSH normal; thyroxine high; T3 high
TSH normal / low; thyroxine low; T3 low
TSH high; thyroxine low; T3 low
TSH low; thyroxine high; T3 high
TSH high; thyroxine normal; T3 high
Submit answer
Reference ranges v
TSH normal / low; thyroxine low; T3 low
TSH high; thyroxine low; T3 low
TSH low; thyroxine high; T3 high
TSH high; thyroxine normal; T3 high
Next question )
Sick euthyroid syndrome
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is

often said that everything (TSH, thyroxine and T3) is low. In the majority
of cases however the TSH level is within the >normal range
(inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and
hence no treatment is usually needed.
Next question )
Save my notes
Q13
A 31-year-old woman presents for review. For the past few months she
has been feeling generally tired and has not had a normal period for
around 4 months. Prior to this she had a regular 30 day cycle. A
pregnancy test is negative, pelvic examination is normal and routine
bloods are ordered:
FBC Normal
U&E Normal
TFT Normal
Follicle-stimulating hormone 41 iu/1 ( < 35 iu/1)
Luteinizing hormone 33 mlU/1 (< 20 mlU/1)
Oestradiol 70 pmol/1 ( > 100 pmol/1)
ovarian cancer
Gonadotropin-producing pituitary adenoma
Turner syndrome
Aromatase enzyme deficiency

Aromatase enzyme deficiency
•• •t • Discuss (2) Improve
Next question )
Premature ovarian failure is defined as the onset of menopausal

symptoms and elevated gonadotrophin levels before the age of 40
years. It occurs in around 1 in 100 women.
Causes
• idiopathic - the most common cause
• chemotherapy
• autoimmune
• radiation
Features are similar to those of the normal climacteric but the actual
presenting problem may differ
• climacteric symptoms: hot flushes, night sweats
• infertility
• secondary amenorrhoea
• raised FSH, LH levels
Next question )
0 Q14
A 61-year-old male is diagnosed with acromegaly after presenting with

headaches, sweaty palms and a change in shoe size. Magnetic
resonance scan has shown a pituitary macroadenoma and he is
planned for transsphenoidal surgery.
What treatment is often used as an adjunct to surgery?
Bromocriptine
Cabergoline
Octreotide
Pegvisomant
Prednisolone
Submit answer
Reference ranges v
Cabergoline
Octreotide
Pegvisomant
Prednisolone
Octreotide can be used as an adjunct to surgery in patients with

acromegaly
Importance: 50
The correct answer is octreotide, a somatostatin analogue which is

often used as an adjunct to surgery resulting in reduced growth
hormone levels and reduction in tumour size.
Bromocriptine is a dopamine agonist used in the medical management

of acromegaly. It is not commonly used as an adjunct to surgery.
Cabergoline is also a dopamine agonist. It is more commonly used in

the medical management of prolactinoma as opposed to acromegaly.
Pegvisomant is a growth hormone receptor antagonist, it is useful for

reducing growth hormone levels but not tumour size. For this reason, it
is not the correct answer.
Prednisolone is not used as an adjunct to surgery. In some instances,

steroids may be used if there were concerns over mass effect or
oedema, but this is not mentioned in this stem.
16 8
Next question )
0 Q15
A 58-year-old woman presents to the emergency department with

confusion. She is found to have a raised temperature, tachycardia and
is hypotensive. After further investigation, she is found to be in a
thyrotoxic storm.
Given her presentation what is the best first line treatment?
Beta blockers and propylthiouracil
Adrenaline, propylthiouracil and hydrocortisone
Beta blockers, propylthiouracil and hydrocortisone
Propylthiouracil and hydrocorti'sone
Submit answer
Reference ranges v
Beta blockers and propylthiouracil
Adrenaline, propylthiouracil and hydrocortisone
Beta blockers, propylthiouracil and hydrocortisone
Propylthiouracil and hydrocortisone
Thyrotoxic storm is treated with beta blockers, propylthiouracil

and hydrocortisone
Importance: 50
This question is asking about a woman presenting with confusion,

tachycardia, hypotension and a raise temperature who is found to be in
a thyrotoxic storm (also known as a hyperthyroid crisis). You are asked
for the best first-line treatment in this case which is option 4, beta
blockers, propylthiouracil and hydrocortisone.
Beta blockers are used to treat the tachycardia, however, these as

always would be contraindicated in patients suffering from asthma.
Propylthiouracil is used as an anti-thyroid treatment to help reduce the

effect of raised serum thyroid hormones that are causing her
symptoms.
Hydrocortisone is used to treat any underlying adrenal insufficiency

which is more common in patients suffering from hyperthyroidism and
can also help to reduce serum thyroid hormone levels.
116 11
Next question )
Thyroid storm
Thyroid storm is a rare but life-threatening complication of

thyrotoxicosis. It is typically seen in patients with established
thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic
thyroxine excess does not usually result in thyroid storm.
Precipitating events:
• thyroid or non-thyroidal surgery
• trauma
• infection
• acute iodine load e.g. CT contrast media
Clinical features include:

• fever > 38.s0 c
• tachycardia
• confusion and agitation
• nausea and vomiting
• hypertension
• heart failure
• abnormal liver function test - jaundice may be seen clinically
Management:
• symptomatic treatment e.g. paracetamol
• treatment of underlying precipitating event
• beta-blockers: typically IV propranolol
• anti-thyroid drugs: e.g. methimazole or propylthiouracil
• Lugol's iodine
• dexamethasone - e.g. 4mg IV qds - blocks the conversion of T 4 to
T3
Next question )
Q16
A 15-year-old girl is investigated for primary amenorrhoea, despite

having developed secondary sexual characteristics at 11 years of age.
On examination she has well developed breasts with scanty pubic hair
and small bilateral groin swellings. What is the most likely diagnosis?
Congenital adrenal hyperplasia
Turner's syndrome
Complete androgen insensitivity syndrome
Mullerian duct agenesis
Submit answer
Reference ranges v
Complete androgen insensitivity syndrome
Mullerian duct agenesis
8' 11 f tt Discuss (2) Improve
Next question )
Androgen insensitivity syndrome
Androgen insensitivity syndrome is an X-linked recessive condition due

to end-organ resistance to testosterone causing genotypically male
children (46XY) to have a female phenotype. Complete androgen
insensitivity syndrome is the new term for testicular feminisation
syndrome
Features
• 'primary amennorhoea'
• undescended testes causing groin swellings
• breast development may occur as a result of conversion of
testosterone to oestradiol
Diagnosis
• buccal smear or chromosomal analysis to reveal 46XY genotype
Management
• counselling - raise child as female
• bilateral orchidectomy (increased risk of testicu lar cancer due to
undescended testes)
• oestrogen therapy
Next uestion
Q17
You review a 52-year-old man who is being investigated for weight gain,
impotence and hypertension. On examination you record a blood
pressure of 180/11 O mm Hg and notice purple striae around his
abdomen. He also has some difficulty getting up from a chair and you
observe generalised decreased muscle strength. Routine bloods are
ordered. Given the likely underlying diagnosis, what are the urea and
electrolytes most likely to show?
Hypocalcaemic metabolic acidosis
Submit answer
Reference ranges v
observe generalised decreased muscle strength. Routine bloods are
ordered. Given the likely underlying diagnosis, what are the urea and
electrolytes most likely to show?
Hypocalcaemic metabolic acidosis

Importance: 50
[ ,. 'f • Discuss (2) Improve
Next question )
Q18
A 47-year-old woman is referred to the general medical clinic. She has

gained 1 O kg in weight in the past 3 months but her main problem is
episodic sweating. These episodes of sweating are associated with
double vision and typical ly occur early in the morning. Clinical
examination is unremarkable. What is the most likely diagnosis?
Bronchial carcinoid
Menopause
Cushing's syndrome
lnsulinoma
Submit answer
Reference ranges v
I lnsulinoma
This is a typical presentation of insulinoma
Next question )
lnsulinoma

Basics
Features
• high C-peptide
Diagnosis
• CT pancreas
Management
• surgery
surgery
Q19
At which point in the menstrual cycle do progesterone levels peak?
Luteal phase
Ovulation
Follicular phase
Levels remain constant throughout cycle
Menstruation
Submit answer
Reference ranges v
Luteal phase
Ovulation
Follicular phase
Levels remain constant throughout cycle
Menstruation
Progesterone is secreted by the corpus luteum following ovulation.
[ ,t •• - Discuss (1) Improve
Next question >
Menstrual cycle
The menstrual cycle may be divided into the following phases:
Days
Menstruation 1-4
Follicular phase (proliferative phase) 5-13
Ovulation 14
Luteal phase (secretory phase) 15-28

Follicular phase
Days 1- 7
Primordial Primary secondary

follicles fomcles folllcles
-+ @ •©>----.
Atresla
r-,. ~ Single, selected
0
-+ \:2, t ~ - - - - - ~~ tertiary follicle
Selection
Constant development Selection of one dominant

of early-stage folllcles secondary follicle begins
(2 months) each new menstrual cycle
ovarian ~cle phases

Folllcular phase LuteaJ phase
5electedtertlary ovulation CorpLS corpus Degradlns
folllcle 1uteur1 alblcans corpus
0 7 14
iJJ 21 28
Day of merstrual cycle
U terlne cycle phases

Pro111e 1a t tve
"-tenses phase Sec.-eto~ p has e
M en.st:ruatt o n
0 7 14 2i 2B
Day cf menstr ual cy -cle
Pituitary ovulation FSH

hormone levels - LH
7 14 21 28
Ovarian - Estrogen
hormone levels - Progesterone
0 7 14 21 28
Day of menstrual cycle
Follicular phase Luteal phase
{proliferative phase) (secretory phase)
Ovarian A number of follicles Corpus luteum

histology develop.
One follicle will become

dominant around the mid-
follicular phase
Endometrial Proliferation of Endometrium

histology endometrium changes to
secretary lining
under influence of
progesterone
Hormones A rise in FSH results in the Progesterone

development of follicles secreted by corpus
which in turn secrete Iuteu m rises
oestradiol through the luteal
phase.
When the egg has matured,
it secretes enough If fertilisation does
oestradiol to trigger the not occur the
acute release of LH. This in corpus luteum will
turn leads to ovulation degenerate and
progesterone levels
fall
Oestradiol levels
also rise again
during the luteal
phase

Cervical Following menstruation the Under the influence
mucus mucus is thick and forms a of progesterone it
plug across the external os becomes thick,
scant, and tacky
Just prior to ovulation the
mucus becomes clear,
acellular, low viscosity. It
also becomes 'stretchy' - a
quality termed spinnbarkeit
Basal body Falls prior to ovulation due Rises following

temperature to the influence of oestradiol ovulation in
response to higher
progesterone levels
Next question )
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Q20
Which one of the following is most likely to be seen in a patient with

multiple endocrine neoplasia (MEN) type I?
Phaeochromocytoma
lnsulinoma
Medullary thyroid carcinoma
RET gene
Submit answer
Reference ranges v
lnsulinoma
Medullary thyroid carcinoma
RET gene
[ "' 'f • Discuss Improve
Next question )
Q21
A 45-year-old man presents with bitemporal hemianopia and spade-like

hands. What is the most appropriate next test?
Early morning growth hormone
Pituitary MRI
Insu lin-like growth factor 1 (IGF-1)
Short ACTH test
Submit answer
Reference ranges v
Pituitary MRI
Insulin-like growth factor 1 (IGF-1 )
Short ACTH test
Serum IGF-1 levels are now the first-line test for acromegaly
Importance: 50
[ ,. 'f ft Discuss (2) Improve ]
Next question )
Acromegaly: investigations
Growth hormone (GH) levels vary during the day and are therefore not
diagnostic.
Serum IGF-1 levels have now overtaken the oral glucose tolerance test
(OGTT) with serial GH measurements as the first-line test. The OGTT
test is recommended to confirm the diagnosis if IGF-1 levels are raised .
The Endocrine Society guidelines suggest the following:
1. 1 We recommend measurement of JGF-1 levels in patients with

typical clinical manifestations of acromegaly, especially those with
acral and facial features.
1. 5 In patients with elevated or equivocal serum IGF-1 levels, we

recommend confirmation of the diagnosis by finding lack of
suppression of GH to < 1 µg/ L following documented
hyperglycemia during an oral glucose load.
Serum IGF-1 may also be used to monitor disease
Oral glucose tolerance test

• in normal patients GH is suppressed to< 2 mu/ L with
hyperglycaemia
• in acromegaly there is no suppression of GH
• may also demonstrate impaired glucose tolerance which is
associated with acromegaly
A pituitary MRI may demonstrate a pituitary tumour.

Q22
A 64-year-old patient is prescribed pegvisomant for the treatment of

acromegaly. What is the mechanism of action of pegvisomant?
IGF-1 receptor antagonist
IGF-1 receptor agonist
Growth hormone receptor agonist
Long-acting somatostatin analogue
Submit answer
Reference ranges v
IGF-1 receptor agonist
Growth hormone receptor agonist
Long-acting somatostatin analogue
,, f
11 tit Discuss Improve
Next question )
Next question )

Dopamine agonists
• may be used as an adjunct t o surgery
Pegvisomant
• once daily s/c administration
mass effect

Next question >

Q1
A 28-year-old woman with polycystic ovarian syndrome consults you as

she is having problems becoming pregnant. She has a past history of
oligomenorrhea and has previously recently stopped taking a combined
oral contraceptive pill. Despite stopping the pill 6 months ago she is still
not having regular periods. Her body mass index is 28 kg/ m"2. Apart
from advising her to lose weight, which one of the following
interventions is most effective in increasing her chances of conceiving?
Metformin
Bromocriptine
Laparoscopic ovarian cautery
Clomifene
Orlistat
Submit answer
Reference ranges v
I Clomifene
Orlistat
Infertility in PCOS - clomifene is superior to metformin

Importance: 50
Whilst metformin has a role in the management of infertility it should be

used second-line to anti-oestrogens such as clomifene. Simi lar
questions to this often appear in which clomifene is not an option, in
this case metformin is clearly the right answer.
,6 •• flt Discuss (1) Improve ]
Next question )

General
Hirsutism and acne
• a coc pill may be used help manage hirsutism. Possible options
include a third generation coc which has fewer androgenic
thromboembolism
• spironolactone, flutamide and fmasteride may be used under
Infertility
stimulate ovulation
• gonadotrophins

Next question )
Q2
A 49-year-old female was admitted to the emergency department with

confusion . A history is unobtainable due to this confusion, with a
Glasgow coma scale score of 13/ 1 5. Hospital records note a 2-month
background of recurrent urinary tract infections (UTl 's) and recent
admission for urosepsis. Her past medical history includes: Type 2
diabetes mellitus, hypertension, hypercholesterolaemia and a hiatus
hernia.
On examination the patient is cool peripherally with a cap refill of 3

seconds, dry mucus membranes, heart sounds 1+2+0, vesicular breath
sounds, abdomen was soft, but tender over the suprapubic area. There
was no rigidity or guarding and bowel sounds were present.
Observations: Respiratory rate 16 breaths per minute, saturations 98%

on air, blood pressure 80/ 58mmHg, heart rate 122 beats per minute,
temperature 38.4°C and capillary glucose 16 mmol/L.
Urine dip showed:
Nitrites +++
Leucocyte est erase +++
Blood +
Glucose +++
Ketones
Prot ein
Ketones
Protein
Which medication is likely to contributing to the cause of her

presentations?
Metformin
Tolbutamide
Dapaglifozin
Sitagliptin
Exanetide
Submit answer
Reference ranges v
I Olbutam1de
Dapaglifozin
Sitagliptin
Exanetide
Dapagliflozin is a member of the glofozin anti-diabetic drugs. The

medication works by inhibiting the sodium-glucose transport proteins
(SGLT2), which reabsorbs glucose in the proximal tubule. The drug has
recently been licensed by national institute of clinical excellence (NICE)
for the treatment of type 2 diabetes mellitus. Dapagliflozin can be tried
if blood sugars are poorly controlled following commencement of
metformin and the patient is unable to take a sulfonylurea. Common
side effect s are often secondary to the glycosuria, which include
increased predisposition of urinary tract infection and dehydration.
.. •t tit Discuss (5) Improve
Next question )

Whilst it is well known that insulin resistance and insufficient 8-cell


These drugs increase insulin secretion and inhibit glucagon secretion .
One of the major advances of GLP-1' mimetics is that they typically

meal.
once a day.

I
comorbidities.
NICE like patients to have achieved a 11 mmol/mol (1%) reduction in


Dipeptidyl peptidase-4 (DPP-4) inhibitors ( e.g. Vildagliptin, sitagliptin)
Key points

Next question )
Q3
An elderly male with T2DM was taken to the Emergency Department

with confuslonw sweating, and ataxia. He is prescribed thiamine,
metformln, gliclazide, and atorvastatin. BM was measured as 1.3
mmol/L with paramedics and, after administration of 100ml IV dextrose
20%, returned to 5.4 mmol/L.
You are called to see the patient in the acute medical unit as his BM has
dropped to 1.8 mmol/ L.
What is the most likely underlying cause?
Low glycogen stores secondary to chronic alcoholism
Metformin associated lactic acidosis
Starvation
Sulfonylurea-induced hypoglycaemia
Wernicke's encephalopathy
Submit answer
Reference ranges v
Metformin associated lactic acidosis
Starvation
Sulfonylurea-induced hypoglycaemia
Werni cke's encephalopathy
In sulphonylurea overdoses, patients are at risk of recurrent

hypoglycaemia
Importance: 50
Sulphonylureas are long-acting anti-glycaemic agents with the potential

to cause recurrent hypoglycaemia.
Glycogen stores are low in chronic alcoholism preventing the use of

glucagon as an effective treatment for hypoglycaemia. Wernicke's
encephalopathy may be precipitated by administration of glucose
before thiamine.
[ ,6 If tll Discuss (6) Improve ]
Next question)
Next question )
Hypoglycaemia
Causes
• liver failure
• alcohol


Next question )
B I c-:,
Q4
A 49-year-old woman with type 2 diabetes mellitus is being considered

for exenatide therapy. Which one of the following is not part of the NICE
criteria for starting or continuing this drug?
BMI > 35 kg/m"2
Greater than 1.0 percentage point HbA 1 c reduction after 6

months
Has failed with insulin therapy
Has type 2 diabetes mellitus
Weight loss > 3% at 6 months
Submit answer
Reference ranges v
Has failed with insulin therapy
Has type 2 d iabetes mellitus
Weight loss > 3% at 6 months
Patients do not need to have been on insulin prior to using exenatide
[ ,6 .. .. Discuss Improve ]
Next question )



CamSc.an,ner ~ '....,.i;lo-" ~~I



meal.
once a day.


• BMI >= 35 kg/m 2 in people of European descent and there are
• BMI < 35 kg/m 2 and insulin is unacceptable because of
comorbidities.

Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points

Next question )
B / ~ A ... :: J= = ... T r., ~ ... ~ c-:::,
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QS
A 36-year-old woman who presented with a goitre is diagnosed with

autoimmune thyroiditis. Which one of the following types of thyroid
cancer is she predisposed to developing?
Anaplastic
Lymphoma
Medullary
Follicular
Papillary
Submit answer
Reference ranges v
Lymphoma
Medullary
Follicular
Papillary
Hashimoto's thyroiditis is associated with thyroid lymphoma

Importance: 50
• If tt Discuss Improve
Next question >
Thyroid cancer

hormones
Main points
Type Percentage

prognosis
Follicular 20%


thyroiditis

Further information
Type Notes



adenoma.
carcinoma tissue
cases

Next question )
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Q6
Which one of the following processes is responsible for ketone

production during diabetic ketoacidosis?
Glycogenolysis
Exchange with hydrogen ions in the collecting ducts
Gluconeogenesis
Decreased plasma bicarbonate levels
Lipolysis
Submit answer
Reference ranges v
Exchange with hydrogen ions in the colle cting duct s
Gluconeogenesis
Decreased plas ma bicarbonate levels
Lipolysis
the
The low-insulin cond ition s seen in diab etic keto acid osis stim ulate
-
process of lipolysis and the production of the ketone bodies, beta
bolic
hydroxybutyrate and acetoacetate, which can be used as meta
fuel.
[ ,. 'f • Disc uss (1) Improve ]
Nex t ques tion )
CamScon,er ~ ....,...., c..>~ •

Q7
A 27-year-old man is reviewed in a fertility clinic. Semen analysis has

revealed azoospermia. On examination at the previous appointment he
was noted to be 1.83 metres tall with a body mass index of 25 kg / m"2.
A degree of gynaecomastia is noted, testicular volume is around 10ml
bilaterally and his visual fields were normal. Which investigation is likely
to be diagnostic?
FISH analysis of DNA
Prolactin level
Karyotype
MRI pituitary
PCR analysis of DNA
Submit answer
Reference ranges v
Karyotype
MRI pituitary
PCR analysis of DNA
Klinefelter's? - do a karyotype
Importance: 50
Next question )
Klinefelter's syndrome is associated with karyotype 47, XXV.
Features
• infertile
Next question )
Q8
Each one of the following is seen in Klinefelter's syndrome, except:
Small, firm testes
Lack of secondary sexual characteristics
Inferti Iity
Increased incidence of breast cancer
Reduced gonadotrophin levels
Submit answer
Reference ranges v
Increased incidence of breast cancer
Reduced gonadotrophin levels
Klinefelter's syndrome - elevated gonadotrophin levels

Importance: 50
[ ,6 " .- Discuss Improve
Next question )
Klinefelter's syndrome is associated with karyotype 47, XXV.
Features
• infertile
Next question )
Q9
A 34-year-old woman presents with palpitations, tremor and heat

intolerance. She is diagnosed with Graves' disease and started on
carbimazole. What is the mechanism of action of this drug?
Inhibits 5'-deiodinase reducing production of T3
Increases renal excretion of carbimazole
Blocks uptake of iodine to thyroid gland by reducing levels of

hydrogen peroxide
Blocks thyroid peroxidase from coupling and iodinating the

tyrosine residues on thyroglobulin
Increases rate of thyroxine breakdown by thyroid peroxidase
Submit answer
Reference ranges v
Blocks thyroid peroxidase from coupling and iodinating the tyrosine
residues on thyrog lobulin
Increases rate of thyroxine breakdown by thyroid peroxidase
Carbimazole blocks thyroid peroxidase from coupling and

iodinating the tyrosine residues on thyroglobulin _. reducing
thyroid hormone production
Importance: 50
116 f
Next question )
Carbimazole
Carbimazole is used in the management of thyrotoxicosis. It is typically

given in high doses for 6 weeks until the patient becomes euthyroid
before being reduced.
Mechanism of action
• blocks thyroid peroxidase from coupling and iodinating the
tyrosine residues on thyroglobulin _. reducing thyroid hormone
production
• in contrast propylthiouracil as well as this central mechanism of
action also has a peripheral action by inhibiting 5'-deiodinase
which reduces peripheral conversion of T 4 to T3
Adverse effects
• agranulocytosis
• crosses the placenta, but may be used in low doses during
pregnancy
Q10
A mother brings her 1 5-year-old daughter to see you as she is worried

about her development. She is very tall for her age, has not yet started
her menstrual cycle and has developed dark facial hair. She is referred
to a specialist who diagnoses mild congenital adrenal hyperplasia.
What deficiency is the most common cause of this condition?
17~-hydroxysteroid dehydrogenase deficiency
5-alpha reductase deficiency
11-beta hydroxylase deficiency
Submit answer
Reference ranges v
5-alpha reductase deficiency
21 -hydroxylase deficiency
11-beta hydroxylase deficiency
Congenital adrenal hyperplasia is most commonly due to 21-

hydroxylase deficiency
Importance: 50
21-hydroxylase deficiency is the most common cause of congenital

adrenal hyperplasia making option 4 the correct answer.
17-hydroxylase deficiency is a rare cause of congenital adrenal

hyperplasia, making this option incorrect.
17~-hydroxysteroid dehydrogenase deficiency results in a rare condition

of sexual development, resulting in ambiguous male genitalia or female
external genitalia at birth in a 46XY individual. Patients also have
hypothyroidism, cryptorchidism, metabolic disorders and are infertile.
5-alpha reductase deficiency is an autosomal recessive condition that

affects male sexual development resulting in a genetically male
individual with usually either female or ambiguous genitalia. Some
individuals may have micropenis with hypospadias.
11-beta hydroxylase deficiency is responsible for around 5% of cases of

congenital adrenal hyperplasia making this the second most common
cause.
11• •• • Discuss (1) Improve
Next question )
Congenital adrenal hyperplasia
Overview
• group of autosomal recessive disorders
• affect adrenal steroid biosynthesis
• in response to resultant low cortis ol levels the anter ior pituita ry
secretes high levels of ACTH
• ACTH stimu lates the produ ction of adrenal androgens that may
virilize a female infant
Cause
• 21-hydroxylase deficiency (90%)
• 11 -beta hydroxylase deficiency (5%)
• 17-hydroxylase deficiency (very rare)
- ,I
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p
..•
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I .,,,. c....., ._.,n

Ot fflll'fflH
A 24-year-old female experiences general weakness, muscle cramps
and recurrent renal stones. She is found to be hypertensive and her
bloods reveal the following :
Na+ 133 mmol/L (135 - 145)
K+ 2.6 mmol/L (3.5 - 5.0)
Bicarbonate 35 mmol/L (22 - 29)
Urea 7.2 mmol/ L (2.0 - 7.0)
Creatinine 156 µmol/ L (55 -120)
Calcium 2.3 mmol/L (2.1-2.6)
Phosphate 0.8 mmol/L (0.8-1.4)
Magnesium 0.5 mmol/L (0.7-1.0)
She is diagnosed with a salt-wasting nephropathy named Gitelman's

syndrome.
Which channel does the mutation in this condition target?
It targets the sodium-potassium chloride (Na-K-CI) co-transporter

in the loop of Henle
It targets the Na/ K antiporter pump in the OCT
It targets the epithelial Na channel in the OCT
It targets the Na/ Cl channel co-transporter in the OCT
It targets the aquaporin 2 in the collecting duct

A 24-year-old female experiences general weakness, muscle cramps
and recurrent renal stones. She is found to be hypertensive and her
bloods reveal the following:
Na+ 133 mmol/ L (135 - 145)
K+ 2.6 mmol/L (3.5 - 5.0)
Bicarbonate 35mmol/L (22 - 29)
Urea 7.2 mmol/L (2.0 - 7.0)
Creatinine 156 µmol/ L (55-120)
Calcium 2.3 mmol/L (2.1-2.6)
Phosphate 0.8 mmol/L (0.8-1.4)
Magnesium 0.5 mmol/ L (0.7-1.0)
She is diagnosed with a salt-wasting nephropathy named Gitelman's

syndrome.
Which channel does the mutation in this condition target?
It targets the sodium-potassium chloride (Na-K-CI) co-transporter

in the loop of Henle
It targets the Na/K antiporter pump in the DCT
It targets the epithelial Na channel in the DCT
It targets the Na/Cl channel co-transporter in the OCT

It targets the Na/ Cl channel co-transporter in the DCT
Gitelman's syndrome is due to a reabsorptive defect of the NaCl

symporter in the DCT
Importance: 50
Gitelman syndrome is another rare autosomal recessive disorder which

occurs due to a mutation causing a resorptive defect of the sodium
chloride co-transporter. Its pathogenesis is similar to the mechanism of
a thiazide diuretic. It is characterised by hypokalemia-hypomagnesemia
and alkaline urine.
Bartter syndrome includes a mutation causing a defect in the Na-K-CI

co-transporter.
Liddle's syndrome includes a mutation causing a defect in epithelial

sodium channels located in the DCT.
Aquaporin 2 is controlled by vasopressin. In diabetes insipidus, the

kidneys do not respond to aquaporin 2.
The Na/K antiporter pump serves in regulating electrolytes. Disruption

of this antiporter is loosely associated with cardiovascular disease,
diabetes, neurological disorders and more.
116 if • Discuss (6) Improve
Next question >

[ .. .. • Discuss (6) Improve ]
Next question )
Gitelman's syndrome
Gitelman's syndrome is due to a defect in the thiazide-sensitive Na+ Cl-

transporter in the distal convoluted tubule.
Features
• normotension
• hypokalaemia
• hypocalciuria
• hypomagnesaemia
• metabolic alkalosis
Next question )
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0 Q12
A 29-year-old woman has just found out she is pregnant for the second
time. Her first pregnancy was complicated by gestational diabetes.
Following her first pregnancy she was told she was no longer diabetic.
Check HbA 1 c immediately
Start metformin and ask the woman to self-monitor glucose
Do oral glucose tolerance test as soon as possible after booking
Do oral glucose tolerance test at 16-18 weeks
Submit answer
Reference ranges v
Do oral glucose tolerance test as soon as possible after booking
NICE have recently updated their guidelines. Women who are at risk of
gestational diabetes should have an oral glucose tolerance test as soon
as possible after booking, rather than waiting to 16-18 weeks as was
previously advocated.
[ ,6 •• - Discuss (1) Improve
Next question >
Pregnancy: diabetes mellitus
Diabetes mellitus may be a pre-existing problem or develop during

pregnancy, gestatio nal diabetes. It complic ates up to 1 in 20
pregnancies. NICE estimat e the followin g breakdown:
• 87.5% have gestational diabetes
• 7.5% have type 1 diabetes
• 5% have type 2 diabetes
Risk factors for gestational diabetes

• BMI of > 30 kg/m 2
• previous macros omic baby weighing 4.5 kg or above
• previous gestational diabetes
• first-degree relative with diabetes
• family origin with a high prevalence of diabetes (South Asian,
black Caribbean and Middle Eastern)
Screening for gestational diabetes
• women who've previously had gestational diabetes: oral glucose
tolerance test (OGTT) should be performed as soon as possible
after booking and at 24-28 weeks if the first test is normal. NICE
also recommend that early self-monitoring of blood glucose is an
alternative to the OGTTs
• women with any of the other risk factors should be offered an
OGTT at 24-28 weeks
Diagnostic thresholds for gestational diabetes

• these have recently been updated by NICE, gestational diabetes is
diagnosed if either:
• fasting glucose is >= 5.6 mmol/I
• 2-hour glucose is >= 7.8 mmol/I
Management of gestational diabetes

• newly diagnosed women should be seen in a joint diabetes and
antenatal clinic within a week
• women should be taught about selfmonitoring of blood glucose
• advice about diet (including eating foods with a low glycaemic
index) and exercise should be given
• if the fasting plasma glucose level is < 7 mmol//I a trial of diet and
exercise should be offered
• if glucose targets are not met within 1-2 weeks of altering
diet/exercise metformin should be started
• if glucose targets are still not met insulin should be added to
diet/exercise/metformin
• if at the time of diagnosis the fasting glucose level is >= 7 mmol/I
insulin should be started
• if the plasma glucose level is between 6-6.9 mmol/I, and there is
evidence of complications such as macrosomia or hydramnios,
insulin should be offered
CamScanner -! W~ :.i.;,-~ \
• glibenclamide should only be offered for women who cannot
tolerate metformin or those who fail to meet the glucose targets
with metformin but decline insulin treatment
Management of pre-existing diabetes

• weight loss for women with BMI of > 27 kg/m"2
• stop oral hypoglycaemic agents, apart from metformin, and
commence insulin
• folic acid 5 mg/ day from pre-conception to 12 weeks gestation
• aspirin 75mg/ day from 12 weeks until the birth of the baby, to
reduce the risk of pre-eclampsia
• detailed anomaly scan at 20 weeks including four-chamber view
of the heart and outflow tracts
• tight glycaemic control reduces complication rates
• treat retinopathy as can worsen during pregnancy
Targets for self monitoring of pregnant women (pre-existing and

gestational diabetes)
Time Target
Fasting 5.3 mmol/I
1 hour after meals 7.8 mmol/ I, or:
2 hour after meals 6.4 mmol/I
Next question )
B / ~ A . . . ·-
■- 2,-= -- . . .
l
Q13
An insulin stress test is most usefu l in t he invest igat ion of:
Glucagonoma
lnsulinoma
Addison's disease
Hypopituitarism
Diabetes mellitus
Submit answer
Reference ranges v
Addison's disease
I Hypo pituita rism
Diabetes mellit us
Insulin stress tests are also occasionally used to differentiate Cushing's

from pseudo-Cushing's
[ ,. " tt Discuss (3) Improve ]
Next ques tion>
Insulin stress test
Basics
• used in investigation of hypopituitarism
• IV insulin given, GH and cortis ol levels measured
• with norma l pituitary functi on GH and cortis ol should rise
Contraindications
• epilepsy
• ischa emic heart disease
• adrenal insufficiency
Next question >
B I l!J A ... 21-: =-.

Q14
You review a 70-year-old who has a long past medical history and is on
multiple drugs. He has developed excessive amounts of breast tissue
bilaterally. Which one of the following drugs is most likely to be
responsible?
Tamoxifen
Terbinafine
Amiodarone
Goserelin (Zoladex)
Lymecycline
Submit answer
Reference ranges v
Score: 0%
Goserelin (Zoladex)
Lymecycline
Goserelin is a gonadorelin analogue used in the treatment of advanced

prostate cancer. Tamoxifen may be used to treat gynaecomastia.
[ •• If tt Discuss (2) Improve ]
Next question >
Gynaecomastia

It is important to differentiate the causes of galactorrhoea ( due to the
• physiological : normal in puberty
• liver disease
• hyperthyroidism
• haemodialysis
• cimetidine
• digoxin
• cannabis
• finasteride

• tricycl ics
• isoniazid
• heroin
• busulfan
• methyldopa
Next question >
B I A .... ·-
·-
12-: == ... c-:>
=
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Q15
A 73-year-old female present with urge incontinence having a significant

impact on her quality of life. She has undergone supervised bladder
training with no improvement in symptoms and is keen to trial
medication. She has a past medical history of atrial fibrillation, well-
controlled hypertension and recurrent urinary retention .
What would be the most appropriate first-line treatment?
Mirabegron
Oxybutynin
Tolterodine
Surgical repair
Submit answer
Reference ranges v
I Mirabegron
Oxybutynin
Tolterodine
Surgical repair
Antich olinerg ics for urge incont inence are associ ated with
confus ion in elderly people - mirabe gron is a prefera ble alterna tive
Importance: 50
The key to this question is to recognise that antimu scarin ics the usual
treatm ent for urge incont inence are contra indicat ed in patien ts with a
history of urinary retention . As such mirabe gron is the correc t answer.
Oxybutynin is an antimu scarin ic and would be contra indicat ed in this

patient.
Pelvic floor exercises are used in the treatm ent of stress incont inence
and are unlikely to have an effect in patien ts with pure urge
incontinence.
Tolterodine is also an antimu scarin ic and should not be used in a

history of urinary retention.
Surgical repair would be used in patien ts with stress incont inence that
has not improved with pelvic floor exercises and as such is not the
correc t answer.
[ •• I 'f I tt Discuss (3) Improve

CamScanner~ '..J~ ~ j,,-,&a:'I
Q16
What is the mechanism of action of exenatide?
Glucagon inhibitor
lncretin inhibitor
Submit answer
L___ _ _ _ _ _ _ _ _ R_e_fe_re_n_c_e_ra_n_g_es_v
_ _ _ _ _ _ _ _ _ _]
lncretin inhibitor
Exenatide = Glucagon-like peptide-1 (GLP-1) mimetic

Importance: 50
[ 1• 1f tt Discuss (1) Improve
Next question )
Q1 7
A 23-year-old woman is admitted to the intensive care unit following an

episode of diabetic ketoacidosis. On admission her Glasgow coma
scale was 7/ 15. Collateral history revealed long-standing type 1
diabetes mellitus with poor glycaemic control.
Arterial blood gases:
pH 7.12
paC02 3.1 kPa
pa02 12.2 kPa
HC03 3 mmol/1
Capillary Glucose: 33mmol/L
Urine dip:
glucose +++
ketones +++
protein
nitrites
Leucocyte esterase -
The patient was intubated and successfully treated with intravenous

fluids, insulin and venous thromboembolism prophylaxis.
On discharge her GP undertook a routine screen of blood tests.

Which of the following thyroid function tests results would be in
keeping with her presentation?
TSH - high, T 4 - Low, T3 high
TSH - high, T 4 - normal, T3 normal
TSH - low, T 4 - Low, T3 high
TSH - low, T 4 - normal, T3 normal
TSH - normal, T 4 - Low, T3 low
Submit answer
Reference ranges v
I TSH - normal, T4 - Low, T3 low
Sick euthyroid syndrome is a reversible state of abnormal thyroid

function tests due to a non-thyroidal illness, without pre-existing
hypothalamic-pituitary or thyroid gland dysfunction. By definition, after
recovery of the non-thyroidal illness, thyroid function tests should revert
back to normal.
Causes of sick euthyroid include: myocardial infarctions, starvation,

burns, trauma, surgery, malignancy, diabetic ketoacidosis, any organ
failure and inflammatory conditions.
The pathology postulated is the down regulation of type 1 deiodinase,

reducing the peripheral conversion of T 4 to T3 and thus reducing the
basal metabolic rate during periods of stress. Upregulation of type 3
deiodinase to inactive (reverse) T3 also aids to reducing basal
metabolic rate.
116 11, • Discuss (2) Improve
Next question >
Sick euthyroid syndrome
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is

often said that everything (TSH, thyroxine and T3) is low. In the majority
of cases however the TSH level is within the >normal range
(inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and
hence no treatment is usually needed.
Q18
A patient with type 2 diabetes is reviewed in clinic. He is currently taking

metformin but his diabetes control remains poor. As he has an erratic
lifestyle consideration is given to starting repagl inide. What is the
mechanism of action of this drug?
Agonist to the PPAR-gamma receptor
Activates an ATP-dependent K+ channel on the cell membrane of

pancreatic beta cells
Submit answer
Reference ranges v
Activates an ATP- +channel on the cell membrane of

dependent K pancreatic beta cells
Meglitinides - bind to an ATP-dependent K+(KATP) channel on the

cell membrane of pancreatic beta cells
Importance: 50
[ ,. 'f • Discuss (4) Improve
Next question >
Meglitinides
Meglitinides (e.g. repaglinide, nateglinide)

• increase pancreatic insulin secretion
• like sulfonylureas they bind to .an ATP-dependent K+(KArP) channel
on the cell membrane of pancreatic beta cells
• often used for patients with an erratic lifestyle
• adverse effects include weight gain and hypoglycaemia (less so
than sulfonylureas)
Next question >

Q19
A 31-year-old female with polycystic ovarian syndrome consults you as

she is troubled with excessive facial hair. Switching her combined oral
contraceptive pill to co-cyprindiol has had no effect. On examination
she has hirsutism affecting her moustache, beard, and temple areas.
What is the most appropriate treatment?
Topical salicylic acid
Topical adapalene
Oral clomifene
Topical eflornithine
Topical tazarotene
Submit answer
Reference ranges v
Topical eflornithine
Topical tazarotene
116 11
Next question )

General
Hirsutism and acne

• a COC pill may be used help manage hirsutism. Possible options
include a third generation COC which has fewer androgenic
thromboembolism
Cam Sconner ...,, ',&~ .G. ~ I
• spironolactone, flutamide and flnasteride may be used under
Infertility
stimulate ovulation
• gonadotrophins

Next question )
B / ~
Save my notes
Q20 Jr::"J
Which one of the following statements regarding glucagon-like peptide-

1 (GLP-1) is incorrect?
Secreted in response to an oral glucose load
Increased levels are seen in type 2 diabetes mellitus
Secreted by the small intestine
Responsible for the incretin effect
Submit answer
Reference ranges v
Increased levels are seen in type 2 diabetes mellitus
Secreted by the small intestine
Responsible for the incretin effect
Decreased levels of GLP-1 are seen in type 2 diabetes mellitus
[ •• •• • Discuss Improve ]
Next question >

Q1
Which one of the following is least associat ed with hyperca lcaemia?
Sarcoidosis
Thiazide diuretics
Monoclonal gammopathy of uncertain significance
Submit answer
Reference ranges v
Thiazide diuretics
Monoclonal gammopathy of uncertain significance
One of the key differentiating features between monoclonal

gammopathy of uncertain significance (MGUS) and myeloma is the
absence of complications such as immune paresis, hypercalcaemia
and bone pain
,6 " - Discuss Improve ]
Next question )
a6 If tt Discuss Improve
Next question )


• sarcoidosis*
• acromegaly
• thyrotoxicosis
• dehydration
• Paget's disease of the bone**


Next question )
B I A ...
Q2
A 46-year-old woman is referred to endocrine with a tender neck

swelling. Blood results are as follows:
TSH <0.1 mU/ 1
T4 188 nmol/1
Hb 14.2 g/ dl
Pit 377 * 109/ 1
WBC 6.4 * 109 / 1
ESR 65 mm/ hr
Technetium thyroid scan shows decreased uptake globally
Acute bacterial thyroiditis
Subacute thyroiditis
Submit answer
Subacute thyroiditis
Subacute thyroiditis is suggested by the tender goitre, hyperthyroidism

and raised ESR. The globally reduced uptake on technetium thyroid
scan is also typical
a6 If • Discuss (3) Improve
Next question )


ESR
• phase 2 (1-3 weeks): euthyroid
Investigations
Management
• thyroid pain may respond to aspirin or other NSAI Ds
Q3
A 26-year-old obese female is investigated for menstrual disturbance. A

diagnosis of polycystic ovarian syndrome is made. Which of the
following findings is most consistently seen in polycystic ovarian
syndrome?
Obesity
Hirsutism
Ovarian cysts on ultrasound
Raised LH:FSH ratio
Clitoromegaly
Submit answer
Reference ranges v
Hirsutism
Ovarian cysts on ultrasound
Raised LH :FSH ratio
Clitoromegaly
Polycystic ovarian syndrome - ovarian cysts are the most

consistent feature
Importance: 50
Whilst all of the features listed above may be seen in polycystic ovarian
syndrome, ovarian cysts are the most consistent feature.
Next question )
Next question)
Polycystic ovarian syndrome: features and

investigation
Polycystic ovary syndrome (PCOS) is a complex condition of ovarian

age. The aetiology of PCOS is not fully understood. Both
hyperinsulinaemia and high levels of luteinizing hormone are seen in
PCOS and there appears to be some overlap with the metabolic
syndrome.
Features
• subfertility and infertility
• menstrual disturbances: oligomenorrhea and amenorrhoea
• hirsutism, acne (due to hyperandrogenism)
• obesity
• acanthosis nigricans (due to insulin resistance)
Investigations
• pelvic ultrasound: multiple cysts on the ovaries
• FSH, LH, prolactln, TSH, and testosterone are useful
investigations: raised LH:FSH ratio is a 'classical' feature but is no
longer thought to be useful in diagnosis. Prolactin may be normal
or mildly elevated. Testosterone may be normal or mildly elevated
- however, if markedly raised consider other causes
• check for impaired glucose tolerance
Next question )
B I fj A .,,. 2=
1- - - ..,.
T I""
0 Q4
A 45-year-old woman with Graves' disease comes for review. She has
recently been diagnosed with thyroid eye disease and is being
considered for radiotherapy. Over the past three days her right eye has
become red and painful. On examination there is proptosis and
erythema of the right eye. Visua l acuity is 6/ 9 in both eyes. What
complication is she most likely to have developed?
Exposure keratopathy
Optic neuropathy
Carbimazole-related neutropaenia
Central retinal vein occlusion
Sjogren's Syndrome
Submit answer
Reference ranges v
exposure Keratopatny
Optic neuropathy
Carbimazole-related neutropaenia
Central retinal vein occlusion
Sjogren's Syndrome
Next question )
Thyroid eye disease

disease.
Pathophysiology
inflammation
Prevention
disease. Prednisolone mav help reduce the risk
Features
presentation
• exophthalmos
• ophthalmoplegia
Management
• steroids
• radiotherapy
• surgery

or both eyes
• disc swelling
Next question )
QS
A 35-year-old female who has recently being diagnosed with Grave's

disease presents for review 3 months after starting a 'block and replace'
regime with carbimazole and thyroxine. She Is concerned about
developing thyroid eye disease. What is the best way that her risk of
developing thyroid eye disease can be reduced?
Reduce alcohol intake
A diet rich in omega-3 fatty acids
Regular exercise
Stop smoking
Lose weight
Submit answer
Reference ranges v
A 35-year-old female who has recently being diagnosed with Grave's
disease presents for review 3 months after starting a 'block and replace'
regime with carbimazole and thyroxine. She is concerned about
developing thyiroid eye disease. What is the best way that her risk of
developing thyiroid eye disease can be reduced?
Reduce alcohol intake
A diet rich in omega-3 fatty acids
Regular exercise
Stop smoking
Lose weight
Smoking is the most important modifiable risk factor for the

" If - Discuss (1) Improve ]
Next question )
Q6
Which one of the following unwanted effects is most likely to occur in

patients taking gliclazide?
Peripheral neuropathy
Cholestasis
Photosensitivity
Syndrome of inappropriate ADH secretion
Weight gain
Submit answer
Reference ranges v
I Weight gain
---------------
All of the above side-effects may be seen in patients taking

sulfonylureas but weight gain is the most common.
16 11
Next question )
Sulfonylureas

On a molecular level they bind to an ATP-dependent K+(KATP) channel
on the cell membrane of pancreatic beta cells.

• weight gain

secretion
Sulfonylureas should be avoided in breastfeeding and pregnancy.
Next question )
Q7
Which one of t he following statements regard ing the normal menstrual

cycle is incorrect?
A number of follicles develop in the follicular pha se under the

influence of FSH
The luteal phase is al so known as the secretary phase
The follicular phase follows menstruation and occurs around day

5 -13
A surge of FSH causes ovulation
Progesterone levels are low in the follicular phase
Submit answer
Reference ranges v
A surge of FSH causes ovulation
Progesterone levels are low in the follicular phase
LH surge causes ovulation

Importance: 50
" 'f • Discuss (1) Improve ]
Next question )
Menstrual cycle
The menstrual cycle may be divided into t he following phases:
Days
Menstruation 1-4
Follicular phase (proliferative phase) 5-13
Ovulation 14
Luteal phase (secretory phase) 15-28

Folllcular phase
Days 1-7
Prlmordlal Prfmary Secondary

follicles lolllcles folllcles
... •© •® GP
Atresla
Single, selected
© •©>
Selectlon
tertiary folllcle
0
© ~
Atresla
{@
constant development Selectlon of one domtnant

of early-stage folllcles secondary folllcle begins
(2 months) each new menstrual cycle
Ovarian cycle phases

Follicular phase Luteal pflase
Selected tertiary ovuauon
le► =~~;
----f-ol-llc.... \.,:.;~~ 'j
COrpLS corpus DegradJn~
alblcans co,pus
0 7 14 21 28
Day of merstrual cycle
Uterlne cycle phases

Prollt e rat lve
r..tenses phase Sec.-etor>' phase
M enstruatl c,n
0 7 14 21 28
Day of m,enstruaJ cycl e
Pituitary OvulatJon FSH

hormone levels - LH
1~ 0
7 14 21 28
...g
0
ovarian - Estrogen
:c hormone levels - Progesterone
0 7 14 21 28
Day of menstrual cycle
Follicular phase Luteal phase
(proliferative phase) (secretary phase)
Ovarian A number of follicles Corpus luteum

histology develop.
One follicle will become

dominant around the mid-
follicular phase
Endometrial Proliferation of Endometrium

histology endometrium changes to
secretary lining
under influence of
progesterone
Hormones A rise in FSH results in the Progesterone

development of follicles secreted by corpus
which in turn secrete luteum rises
oestradiol through the luteal
phase.
When the egg has matured,
it secretes enough If fertilisation does
oestradiol to trigger the not occur the
acute release of LH. This in corpus luteum will
turn leads to ovulation degenerate and
progesterone levels
fall
Oestradiol levels
also rise again
during the luteal
phase
Cervical Following menstruation the Under the influence
mucus mucus is thick and forms a of progesterone it
plug across the external os becomes thick,
scant, and tacky
Just prior to ovulation the
mucus becomes clear,
acellular, low viscosity. It
also becomes 'stretchy' - a
quality termed spinnbarkeit
Basal body Falls prior to ovulation due Rises following

temperature to the influence of oestradiol ovulation in
response to higher
progesterone levels
Next question )
B J tj
Save my notes
Search
■
Search textbook...
O. Google search on "Menstrual cycle"

01
An 85-year-old comes for review. She has recently had private health
screening and has been advised to see a doctor regarding her thyroid
function tests (TFTs).
TSH 9.2 mU/L
Free thyroxine 14 pmol/L
She is currently well and asymptomatic. What is the most appropriate

management?
Start levothyroxine
Start ca rbimazole
Order a thyroid ultrasound scan
Start levothyroxine + carbimazole ('block and replace')
Repeat TFTs in a few months time
Submit answer
Start carbimazole
Order a thyroid ultrasound scan
Start levothyroxine + carbimazole ('block and replace')
Repeat TFTs in a few months time
This patient has subclinical hypothyroidism. By both the TSH and age
criteria advocated by NICE Clinical Knowledge Summaries she should
be monitored for now.
[ ,. If - Discuss (3) Improve ]
Next question )
Subclinical hypothyroidism
Basics
• TSH raised but T3, T4 normal
• no obvious symptoms
Significance
• risk of progressing to overt hypothyroidism is 2-5% per year
(higher in men)
• risk increased by the presence of thyroid autoantibodies
Management
Not all patients require treatment. NICE Clinical Knowledge Summaries

(CKS) have produced guidelines. Note that not all patients will fall within
the age boundaries given and hence these are guidelines in the broader
sense.
TSH is between 4 - 10mU/L and the free thyroxine level is within the
normal range
• if< 65 years with symptoms suggestive of hypothyroidism, give a
trial of levothyroxine. If there is no improvement in symptoms,
stop levothyroxi ne
• 'in older people (especially those aged over 80 years) follow a
'watch and wait' strategy, generally avoiding hormonal treatment'
• if asymptomatic people, observe and repeat thyroid function in 6
months
TSH is > 10mU/ L and the free thyroxine level is within the normal range
• start treatment (even if asymptomatic) with levothyroxine if<= 70
years
• 'in older people (especially those aged over 80 years) follow a
'watch and wait' strategy, generally avoiding hormonal treatment'
Next question )
B J f!j A •
~ ! l \ / 0 m\t nntoc- I
Q2
A 67-year-old woman presents with lethargy, depression and

constipation. A set of screening blood tests reveals the following:
Calcium 3.05 mmol/ 1
Albumin 41 g/ 1
What is the single most useful test for determining the cause of her
hypercalcaemia?
ESR
Phosphate
Vitamin D level
Parathyroid hormone
ACE level
Submit answer
Reference ranges v
Phosphate
Vitamin D level
Parathyroid hormone
ACE level
Parathyroid hormone levels are useful as malignancy and primary

hyperparathyroidism are the two most common causes of
hypercalcaemia. A parathyroid hormone that is normal or raised
suggests primary hyperparathyroidism.
,6 " tit Discuss (3) Improve ]
Next question )
Q3
A 4-year-old boy is being investigated for failure to thrive and

generalised weakness. His blood pressure is normal. The following
blood results are obtained:
Na+ 137 mmol/1
K+ 3.0 mmol/1
Urea 4.5 mmol/1
Creatlnine 65 µmol/1
Conn's syndrome
Bartter's syndrome
Cushing's syndrome
Liddle's syndrome
Submit answer
I Bartter's syndrome
Cushing's syndrome
Liddle's syndro me
Bartter's syndrome is associated with normotension

Importance: 50
Bartter's syndro me is the most likely diagnosis. Congenital adrenal

hyperplasia due to 21-hydroxylase deficiency is associated with
precoc ious puberty rather than fai lure to thrive in boys. Both Conn's and
Cushing's are assoc iated with hypertension and are not comm on in this
age group.
Liddle 's syndro me is a rare autosomal domin ant condit ion that causes
hypert ension and hypokalaemic alkalosis. It is though t to be caused by
disordered sodium channels in the distal tubules leading to increased
reabsorption of sodium.
Next question )
Next question )
Bartter's syndrome
Bartter's syndrome is an inherited cause (usually autosomal recessive)

of severe hypokalaemia due to defective chloride absorption at the Na+
K+ 2CI- cotransporter (NKCC2) in the ascending loop of Henle. It should
be noted that it is associated with normotension (unlike other endocrine
causes of hypokalaemia such as Conn's, Cushing's and Liddle's
syndrome which are associated w ith hypertension) .
Loop diuretics work by inhibiting NKCC2 - think of Bartter's

syndrome as like taking large doses of furosemide
Features
• usually presents in childhood, e.g. Failure to thrive
• polyuria, polydipsia
• hypokalaemia
• normotension
• weakness
Next question )
B / /!J T I""
Save mv notes l
Q4 fc:::J
A 43-year-old man presents to his GP with t iredness, low mood and

unintentional weight gain of 13kg over the past 4 months. Prior to
feeling like this he recalls having a flu-like illness following which he had
a two-week period of feeling very anxious, shaky and energetic. He
wonders if this is connected.
On examination he has a heart rate of 68 bpm, his blood pressure is

147/83 mmHg and his temperature is 37.1 °c. Examination of his
abdomen and chest are unremarkable and he does not have a goitre or
any palpable lymphadenopathy. He has no family history of note and no
past medical history.
Blood tests to look at his thyroid function show the following:
Thyroid stimulating hormone (TSH) 6.1 mu/I (0.5-5.5 mu/I)
Free T 4 6 pmol/1 (9-18 pmol/1)
What is the most likely cause of this man's symptoms?
Grave's disease
Papillary cancer of the thyroid
Submit answer
Papillary cancer of the thyroid
Subacute thyroiditis causes hyper- then hypothyroidism

Importance: 50
This gentleman has a clinical picture of hypothyroidism with what

appears to be a brief period of hyperthyroidism prior to this. The most
common cause of this is De Quervain's thyroiditis and this would be in
keeping with the history of a viral infection before the initial
hyperthyroid episode. There is a rare form of Hashimoto's in which the
patient has an initial phase of hyperthyroidism before becoming
hypothyroid, however the period of hyperthyroidism is prolonged in
those cases and the clinical picture is often indistinguishable from
Grave's disease. In addition it happens far more commonly in women
than men (around 5 times) and has a strong association with other
auto-immune diseases. The key to this question is what is most likely
and given the relatively brief period of hyperthyroidism (in Hashimoto's
it would be in the order of 6-12 months rather than a few weeks) and the
preceding viral infection, De Quervain's is far more likely.
Grave's disease and toxic multinodular goitre would both present with
hyperthyroidism and papillary thyroid cancer does not produce
thyroxine so would not cause any systemic symptoms.
[ ,6 •• - Discuss (2) Improve ]

Next question ~


ESR
• phase 2 (1-3 weeks) : euthyroid
Investigations
Management
• thyroid pain may respond to aspirin or other NSAIDs
H shimoco's
th~roic:1•115
Grav s' disease
Atruodarone Toxic mu t nodular goitre

Rlod s lhyrold1ll$
Postpartum tnyroid
l1th111m
Q1
A 32 year-old man presents complaining of persistent headaches. He

was diagnosed with hypertension 4 months ago and started on
perindopril. On examination, heart his rate is 75 beats per minute and
blood pressure is 185/11 SmmHg.
Investigations:
Serum potassium 1.9 mmol/L (3.5-5.0)
Plasma aldosterone (after 30 minutes supine) 700 pmol/L (135-400)
Plasma renin activity (after 30 minutes supine) 0.4 pmol/ml/hr (1 .1-2.7)
What is the most likely cause of his hypertension?
Addison disease
Bilateral renal artery stenosis
Coarctation of the aorta
Phaeochromocytoma
Submit answer
Bilateral renal artery stenosis
Coarctation of the aorta
Phaeochromocytoma
I Primary hyperaldosteronism
Primary hyperaldosteronism can present with hypertension,

hypernatraemia, and hypokalemia
Importance: 50
Primary hyperaldosteronism is typically caused by an aldosterone

producing adenoma (Conn's syndrome), other causes include: bilateral
adrenocortical hyperplasia and adrenal carcinoma.
Primary hyperaldosteronism and bilateral renal artery stenosis are

associated with hypokalaemia due raised serum aldosterone, which
causes increased sodium reabsorption and potassium excretion.
Aldosterone is elevated in bilateral renal artery stenosis due to reduced

renal perfusion. Aldosterone is high in primary hyperaldosteronism,
however, serum renin is usually low in primary hyperaldosteronism due
to the resulting hypertension causing excessive renal perfusion, which
results in decreased renin production (negative feedback mechanism).
High renin levels are seen in renal artery stenosis as renal perfusion is
permanently reduced, despite hypertension, due to the stenotic renal
arteries.
(Reference: Oxford handbook of cl inical medicine, 8th ed.pg.220)
at •• - Discuss (7) Improve

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01

A patient with type 2 diabetes mellitus is started on sitagliptin. What is

Dipeptidyl peptidase-4 (DPP-4) inhibitor

Glucagon-like peptide-1 (GLP-1) mimetic

Glucagon-like peptide-1 (GLP-1) mimetic

Gliptins = Dipeptidyl peptidase-4 (DPP-4) inhibitors

•• •• tt Discuss (1) Improve

Diabetes mellitus: GLP-1 and the new drugs

A number of new drugs to treat diabetes mellitus have become

Whilst it is well known that insulin resistance and insufficient 8-cell

Increasing GLP-1 levels, either by the administration of an analogue

Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic.

Exenatide must be given by subcutaneous injection within 60 minutes

Both exenatide and liraglutide may be combined w ith metformin and a

NICE state the following:

Consider adding exenatide to metformin and a sulfonylurea if:

NICE like patients to have achieved a 11 mmol/mol (1 %) reduction in

The major adverse effect of GLP-1 mimetics is nausea and vomiting.

Dipeptidyl peptidase-4 {DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)

NICE guidelines on DPP-4 inhibitors

Next question >

Growth hormone receptor antagonist

Insulin-growth factor 1 antagonist

Growth hormone receptor antagonist

Insulin-growth factor 1 antagonist

Acromegaly is caused by excessive growth hormone.

This question is two-fold. First, one has to recognise the symptoms of

Dopamine agonists were initially used to treat acromegaly but have

Trans-sphenoidal surgery is the first-line treatment for acromegaly in

External irradiation is sometimes used for older patients or following

A 75-year-old woman presents with weight gain, lethargy and

Which of her medications is most likely to be the cause of this

Iron / calcium carbonate tablets can reduce the absorption of

Ferrous sulphate is correct. This woman is presenting with symptoms

Tablets containing iron can reduce the absorption of levothyroxine, and

There is no interaction between levothyroxine and any of the other

116 it • Discuss Improve

CamScanne, -? Y.¥-> i.b . ~I

Side-effects of thyroxine therapy

A 46-year-old man with suspected diabetes mellitus has an oral glucose

Time (hours) Blood glucose (mmol/1)

How should these results be interpreted?

Impaired fasting glucose and impaired glucose tolerance

Impaired glucose tolerance

Impaired fasting glucose

Impaired fasting glucose and impaired glucose tolerance

Impaired glucose tolerance

Impaired fasting glucose

9' 1f • Discuss (1) Improve

Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by either a

If the patient is symptomatic:

If the patient is asymptomatic the above criteria apply but must be

Hb.A1c· <a 41 mmOllmo, - .. mmol.'mo,

I • values equal :o 1h11

In 2011 WHO released supplementary guidance on the use of HbA1c on

Conditions where HbA1 c may not be used for diagnosis:

Impaired glucose tolerance (IGT) is defined as fasting plasma glucose

In type 1 diabetics, a general HbA 1c target of 48 mmol/mol (6.5%)

9' •• tit Discuss Improve