Endocrinologic Disorders

Endocrine Disorders
Thyroid Disorders
Pituitary Gland Disorders
Adrenal Gland Disorders
Diabetes Mellitus (Types 1 and 2)
Treatment of DM Complications
Diabetes Insipidus
Endocrinologic Disorders 1
THYROID DISORDERS - PHARMACOTHERAPY
Introduction
Thyroid hormones affect the function of every organ system

In the child: critical for normal growth & development
In the adult: to maintain metabolic homeostasis
Substantial reservoirs of thyroid hormone in the thyroid gland
and blood provide constant thyroid hormone availability
Triiodothyronine (T3) and thyroxine (T4) are the two biologically

active thyroid hormones
• T3 is four times more potent than T4
• T4 is the major circulating hormone secreted
They are synthesized & stored as amino acid residues of
thyroglobulin
Hypothalamus-pituitary-thyroid axis
Thyroid Hormone Synthesis
 The production of thyroid hormone is regulated in to two main ways
 First, thyroid hormone is regulated by TSH secreted by the
anterior pituitary
• Negative feed back: circulating level of free thyroid hormone
• Positive feed back: TRH
 Second, extrathyroidal deiodination of T4 to T3 is regulated by
a variety of factors including nutrition, nonthyroidal hormones,
ambient temperatures, drugs, and illness
 The growth and function of the thyroid are stimulated by activation

of the thyrotropin receptor by TSH
 TSH stimulates the expression of thyroglobulin and thyroid
peroxidase genes as well as increases apical iodide efflux
THYROID FUNCTION TESTS
 The principal laboratory tests recommended in the initial
evaluation of thyroid disorders are the TSH and the FT4 levels
 Positive thyroid antibodies indicate an autoimmune thyroid

etiology
 Adjuncts to the previous tests include the total T3 (TT3), free T3

(FT3) or FT3 index (FT3I), RAIU and scan, TRAb, ultrasound, and
FNA biopsy
 The FT4 and FT3 are the most reliable tests for the evaluation of
hormone concentrations
Evaluation of thyroid function tests
Hyperthyroid Disorders: Thyrotoxicosis
 A clinical state caused by inappropriately high thyroid

hormone action in tissues, usually due to inappropriately high
tissue thyroid hormone levels
 Results when tissues are exposed to excessive levels of T4,

T3, or both
 In the United States, the prevalence of hyperthyroidism is

about 1.2%, of which 0.5% are clinical and 0.7% are
subclinical
Classification
 Toxic diffuse goiter (Graves’ disease):
• Most common hyperthyroid disorder, comprising an estimated 70%

to 85% of cases.
• The incidence of Graves disease is about 0.5 in 1000, with highest

risk of onset between ages 40 and 60.
• The incidence in men is 1/5 to 1/10 of that in women.
• Graves disease is rare in children

Autoimmune disorder
 Graves disease is an autoimmune disease characterized by T-
cell dependent production of thyrotropin-receptor stimulating
antibodies resulting in hypersecretion of thyroid hormone.
 Anti-thyrotropin-receptor antibodies also stimulate thyroid

follicular hypertrophy and hyperplasia, resulting in goiter
formation.
 Usually includes hyperthyroidism, diffuse thyroid enlargement,

exophthalmos, and less commonly pretibial myxedema and
thyroid acropachy
 Pituitary adenomas:
Produce excessive TSH secretion that does not respond to normal

T3 feedback
 Toxic adenoma
Toxic adenoma is the result of autonomous thyroid hormone

production caused by somatic, activating mutations of genes that
regulate the synthesis of thyroid hormone
A discrete thyroid mass, autonomous, whose function is independent

of pituitary & TSH control
 Toxic multinodular goiter (Plummer disease)
Several autonomous follicles that, if large enough, cause excessive

thyroid hormone secretion
 Follicles with autonomous function coexist with normal or even

nonfunctioning follicles
 Pathogenesis of MNG is thought to be similar to that of toxic

adenoma:
 Diffuse hyperplasia caused by goitrogenic stimuli, leading to
mutations and clonal expansion of benign neoplasms
 Thyrotoxicosis in a MNG occurs:
 When a sufficient mass of autonomous follicles generates enough
thyroid hormone to exceed the needs of the patient
 Painful sub-acute thyroiditis:
Self-limiting inflammation of the thyroid gland caused by

viral invasion of the parenchyma, resulting in the release of
stored hormone
 Drug induced: excessive exogenous thyroid hormone doses,

amiodarone therapy (contains 37% iodine)
Diagnosis
Elevated free T4 serum concentrations
Suppressed TSH conce. (except in TSH-secreting adenomas)
If examination and history do not provide the exact etiology,

radioactive iodine uptake may be employed
Radioactive iodine uptake elevated if thyroid gland is actively and

excessively secreting T4 and/or T3: Graves’ disease, TSH-secreting
adenoma, toxic adenoma, multinodular goiter
Radioactive iodine uptake is suppressed in disorders caused by

thyroiditis or hormone ingestion
Clinical presentation
Wt loss with an appetite: cardinal manifestation
Heat intolerance, Goiter, fine hair
Palpitations/tachycardia, nervousness, anxiety, insomnia
Menstrual disturbances (more infrequent menstruation,

amenorrhea): due to ed metabolism of estrogen
Sweating or warm, moist skin
Exophthalmos and pretibial myxedema in Graves’ disease
Hyperthyroidism: Treatment
Goal of treatment
Minimize or eliminate symptoms
Improve quality of life
Normalize free T4 & TSH concentrations
Minimize long-term damage to organs

Heart disease, arrhythmias, sudden cardiac death, bone
demineralization & fractures
Non-pharmacological methods
 Ablative therapy or Surgical removal of the hyper-secreting

thyroid gland
Surgery should be considered in patients with
A large thyroid gland (>80 g),
Severe ophthalmopathy, and
A lack of remission on anti-thyroid drug treatment
Overall morbidity rate with surgery is 2.7%
Most common complications of surgery: hypothyroidism (49%),

hypoparathyroidism (3.9%) & vocal cord abnormalities (5.4%)
 Traditional preparation of the pt for thyroidectomy includes:
PTU or MMI until the patient is biochemically euthyroid (usually 6-8

wks), followed by the addition of iodides (500 mg/day) for 10-14
days before surgery to the vascularity of the gland
T4 can be added to maintain the euthyroid state while the

thionamides are continued
Propranolol for several wks preoperatively & 7-10 days after

surgery has also been used to maintain a pulse rate of <90bpm
Post-Thyroidectomy Care
 Monitoring for hypocalcemia with serum calcium or intact
parathyroid hormone levels (iPTH)
 Patients may be discharged if they are asymptomatic and if their

serum calcium levels are at least 7.8 mg/dL and stable
 If iPTH levels are below 10 to 15 pg/mL during the immediate

postoperative period, calcium and calcitriol (1,25 vitamin D)
supplementation will probably be needed
 Thyroid hormone supplementation (L-thyroxine) should be initiated

following total thyroidectomy at a daily dose based on the
patient's weight (0.8 mcg/lb or 1.7 mcg/kg).
 Serum TSH measurements every 6 to 8 weeks after surgery,
then at least annually when the TSH is normal and stable
 Thyroid hormone supplementation may not be necessary after

lobectomy for toxic adenoma (TA)
 If the TSH is persistently elevated above the normal range,

thyroid hormone supplementation should be started.
 Serum calcium levels and calcium and calcitriol supplementation

are not necessary after lobectomy for TA
Anti-thyroid Pharmacotherapy
Antithyroid Pharmacotherapy usually reserved for:
 Those awaiting surgical resection
Depletes stored hormone
Minimizes risk of post Rx hyperthyroidism because of thyroiditis
 Those who are not an ablative or surgical candidate
 serious cardiovascular disease, candidate unlikely to be adherent to
radiation safety
 When surgical resection fails to normalize thyroid function
 Those with a high probability of remission with oral therapy with
Graves’ disease
• Mild disease, Small goiter, Low or negative antibody titers
 Those with limited life expectancy
 Those with moderate to severe active Graves ophthalmopathy
Thioureas: PTU, Methimazole
 MOA:
Inhibits iodination (organification) & synthesis of thyroid
hormones by inhibiting coupling
PTU may block T4  T3 conversion in the periphery as well
 Dosing: PTU
Initial: 100 mg PO TID
Maximal: 400 mg PO TID
Once euthyroid, may reduce to 50 mg BID or TID

Recommended over methimazole in the first trimester of
pregnancy because of the risk of embryopathy; can
change to methimazole in second trimester
Methimazole:
Preferred agent for Graves’ disease according to the AACE for
most pts unless in 1st trimester of pregnancy; then use PTU
First-line therapy for most children with Graves disease for 1 to
2 years
Initial: 10–30 mg by mouth once daily (use higher dose in those
with higher baseline free T4 concentrations
Maximal: 40 mg PO TID
Once euthyroid, may reduce to 5-10 mg/day
Note: monthly dose titrations as needed (based on symptoms and
free T4 concentrations);
TSH may remain low months after starting therapy
Early in therapy, total T3 may be a better marker of
efficacy than free T4
Adverse effects of Thioureas
 Hepatotoxicity issue with PTU (boxed warning):
 AACE recommends baseline liver function tests.
Rash, fever, arthralgias, lupus-like symptoms
Agranulocytosis early in therapy (usually within 3 months):
AACE recommends baseline CBC (complete blood cell count);

no routine monitoring recommended.
May repeat if patient becomes febrile or develops pharyngitis
Thioureas: Efficacy
Slow onset in reducing symptoms (4-8 weeks)
Maximal effect may take 4-6 months
Neither drug appears superior to the other in efficacy
On a milligram-to-milligram basis:
Methimazole is 10 times more potent than PTU
Remission rates low: 40%-50%
Remission defined as normal TSH and T4 for 1 year after

discontinuing antithyroid therapy
Oral agents unlikely to cause remission in those with nodular
thyroid disease:
Therapy duration in Graves’ disease

Usually 12-18 months; length of trial may not affect
remission rate
Consider trial off oral therapy if TSH is normal; antibody titers

may help guide decision
Monitor thyroid concentrations every 1-3 months for up to 6-12

months for relapse (abnormal TSH or T4 return)
Nonselective β-blockers
Primarily propranolol; sometimes nadolol
MOA:
Blocks many hyperthyroidism manifestations mediated by β-

adrenergic receptors
Also may block T4  T3 conversion
Propranolol dosing:
Initial: 20-40 mg PO TID or QID
Maximal: 240-480 mg/day

Efficacy:
Primarily used for symptomatic relief: palpitations, tachycardia,
tremor, anxiety
Guidelines recommend use in the elderly, symptomatic patients,

and others with HR >90 bpm. Consider using in all symptomatic
patients
Poor remission rates: 20%-35%
Primary role is treatment of thyroiditis, which is usually self-

limiting, and for acute mgt of symptoms during thyroid storm
Alternatives to β-blockers: clonidine, nondihydropyridine CCBs

 Iodines: Lugol’s solution, saturated solution of KI
MOA:
Inhibits the release of stored thyroid hormone.
Minimal effect on hormone synthesis
Helps decrease vascularity and size of gland before surgery
Dosing:
Usual daily dose: 120-400 mg mixed with juice or water TID
Lugol’s solution: 6.3-8 mg of iodide per drop
Saturated solution of KI: 38-50 mg of iodide per drop
KI tablets: 130 mg tablets contain 100 mg of iodide
Adverse effects:
Hypersensitivity
Metallic taste
Soreness or burning in mouth or tongue
Do not use in the days before ablative surgery (may reduce
uptake of radioactive iodine)
Efficacy:
Limited efficacy after 7-14 days of therapy because thyroid
hormone release will resume
Primary use is temporary before surgery (7-10 days) to shrink

the size of the gland
Used post-ablative therapy (3-7 days) to inhibit thyroiditis

mediated release of stored hormone
Used acutely in thyroid storm
Sub Clinical Hyperthyroidism
 Definition:
Low (below lower limit of reference range) or undetectable TSH

with normal T4
 Risk?
risk of AF in pts >60 years
risk of bone fracture in postmenopausal women
Conflicting data regarding mortality risk
Treatment
Similar with overt hyperthyroidism
Oral anti-thyroid drug therapy alternative to ablative therapy in
young patients with Graves’ disease
β-blockers: controlling CV morbidity, especially with AF
If untreated, screen regularly for the development of overt
hyperthyroidism (free T4 concentrations)
Thyroid Storm
Severe & life-threatening decompensated thyrotoxicosis
Mortality rate may be as high as 20%
Precipitating causes:
Trauma, infection, anti-thyroid agent withdrawal, severe thyroiditis,

postablative therapy (especially if inadequate pretreatment)
Presentation:
Fever, tachycardia, vomiting, dehydration, coma, tachypnea, delirium
Pharmacotherapy
 PTU
Dose: 500-1000 mg DL; then 250 mg Q4 hours
Blocks new hormone synthesis
 Iodide therapy: 1 hr after PTU initiation (dosed as above) to

block hormone release
 β-blocker therapy: esmolol commonly used (can use other agents:

propranolol) to control symptoms & blocks conversion of T4 to T3
 Antipyretic therapy, if needed
Avoid NSAIDs b/c of displacement of protein-bound thyroid
hormones
 Corticosteroid therapy:
Prednisone: 25-100 mg/day in divided doses or equivalent doses
of dexamethasone, hydrocortisone will blunt & delay the in
antibodies to the TSH receptor, thyroglobulin & TPO
Hypothyroidism: Pharmacotherapy
 Hypothyroidism is defined as the clinical and biochemical
syndrome resulting from decreased thyroid hormone production
 Reduced secretion of thyroid hormone by the thyroid gland
 Hypothyroidism is a common endocrine disorder, 5 to 10 times
more common than hyperthyroidism
 Primary hypothyroidism comprises 95% of all hypothyroidism
cases
 Chronic autoimmune thyroiditis (Hashimoto disease) causes most
hypothyroidism in the developed world, followed by hypothalamic
and pituitary pathology
 Globally, iodine deficiency is the most common cause
 Primary hypothyroidism results from failure of the thyroid gland

to secrete sufficient thyroid hormone
 In primary hypothyroidism free T4 and free T3 concentrations

are reduced; thyrotropin concentration is elevated
 In cases of central hypothyroidism (hypothalamic or pituitary

defect), T3, T4 and thyrotropin levels are reduced
 Hypothyroidism may be further classified by its age of onset

(congenital versus acquired), and disease severity (overt or
subclinical)
 Overt thyroidism can be classified as primary or central
 In primary hypothyroidism
 Most often due to chronic autoimmune thyroiditis (Hashimoto
disease), the thyroid gland fails to synthesize and secrete
sufficient active thyroid hormone
 Free thyroxine (T4) is low, resulting in reduced negative
feedback on the pituitary gland leading to elevated
thyrotropin levels
 In chronic autoimmune hypothyroidism, thyroid follicle cell (site of
thyroid hormone synthesis) killing is mediated by autoreactive
cytotoxic T cells (CD8)
 Hypothalamic and Pituitary Disease
 In central hypothyroidism either hypothalamic secretion of

thyrotropin-releasing hormone is compromised, or pituitary
secretion of functional thyrotropin is deficient.
 As a result, free thyroxine (T4) concentration is low, and
thyrotropin concentration is usually low.
 Congenital Hypothyroidism
 can result from various genetic mutations involving thyroid

development, thyroid hormone biosynthesis, thyrotropin
production and response, and cellular response to thyroid
hormone signalling
Diagnosis
 free T4 serum concentrations
 TSH concentrations, usually above 10 mIU/L
Normal or low if central hypothyroidism is the etiology
Thyroid antibodies: anti-thyroid peroxidase & anti-thyroglobulin

autoantibodies
Screen patients older than 60, especially women
Clinical Presentation
Cold intolerance, dry skin, fatigue, lethargy, weakness, wt gain
Bradycardia, slow reflexes, coarse skin & hair, periorbital

swelling,
Menstrual disturbances: more frequent or longer menstruation,

painful menstruation, menorrhagia caused by hypo-metabolism
of estrogen
Goiter: primary hypothyroidism
Management
 Desired Outcomes
 The goals of therapy are to :
• restore normal thyroid hormone concentrations in tissue
• provide symptomatic relief
• prevent neurologic deficits in newborns and children, and
• reverse the biochemical abnormalities of hypothyroidism.
 In thyroid replacement therapy for hypothyroidism, the

therapeutic goal is to achieve a TSH level in the midnormal range
(1 to 2 milliunits/L)
Treatment - Synthetic Thyroid Hormones
 Levothyroxine:
 is the drug of choice for thyroid replacement and suppressive
therapy
• is chemically stable, relatively inexpensive, and free of
antigenicity and has uniform potency.
• Whereas T3 and not T4 is the biologically more active form
of thyroid hormone, levothyroxine administration results in a
pool of thyroid hormone that is readily and consistently
converted to T3
• in this regard levothyroxine may be thought of as a
prohormone
Dosing: initial
1.6 mcg/kg/day: in adults
50 mcg/day: in pts of 50-60 years of age
12.5-25 mcg/day: in those with existing CV disease
Usually dosed in the morning on an empty stomach 30-60 minutes
before breakfast or at bedtime 4 hours after last meal;
Dosed separately from other medications
Dose titration based on response: control of symptoms, normalization

of TSH and free T4
Can or in 12.5-25 mcg/day increments

 The average maintenance dose of levothyroxine for most adults is about
125 mcg/day
 Affected by weight, 1.6 mcg/kg/day and 1.7 mcg/kg/day
 dependent on the patient's age and the presence of associated

disorders, as well as the severity and duration of hypothyroidism
 Monitoring:
4-8 wks is appropriate to assess patient response in TSH
after initiating or changing therapy (about a 7-day half-life
for T4)
begin to fall within hours and are usually normalized within
2 weeks
May take longer for TSH to achieve steady-state
concentrations
Use free T4 rather than TSH if central/secondary
hypothyroidism; obtain sample before daily dosing of T4
Consider individualization, monitoring using TSH
 In general, the increase in thyroxine dosage can be based on the
initial amount of TSH elevation
• Serum TSH between 5 to 10 milli IU/L: increase dose is 25

to 50 mcg/day
• Serum TSH between 10 to 20 milli IU/L: increase in 50 to

75 mcg/day
• Serum TSH over 20 milli IU/L: average increase in

thyroxine dose is 75 to 100 mcg/day
Liothyronine: T3
Chemically pure with known potency & has a shorter half-life of
1.5 days
Although it is widely used diagnostically in the T3-suppression

test, T3 has some clinical disadvantages:
higher incidence of cardiac adverse effects, higher cost &

difficulty in monitoring with conventional laboratory tests
Liotrix: T4:T3 (4:1)
A combination to mimic natural hormonal secretion
Chemically stable & pure & has a predictable potency
Limitations to this product are high cost & lack of therapeutic
rationale b/c 35% of T4 is peripherally converted T3
S/Es of Synthetic Thyroid Hormones
 Serious untoward effects are unusual if dosing is appropriate and

the patient is carefully monitored during initial treatment
 Excessive doses of thyroid hormone may lead to heart failure,

angina pectoris, and myocardial infarction; rarely, the latter
may be caused by coronary artery spasm
 reduce or stop therapy for one week, and then cautiously
restart at a lower dose
 cardiovascular disease, underlying; initiate therapy at a lower
dose
 elderly; increased risk of cardiovascular effects; initiate
therapy at a lower dose
Pregnancy: consideration
 Increased iodine intake is required in pregnant and lactating women
 In hypothyroid pregnant women with adequate iodine intake,

levothyroxine is the treatment of choice to avoid adverse obstetrical and
neonatal outcomes
 Larger thyroxine replacement doses are required in pregnant women
 Because of the increased requirements during pregnancy, the full

replacement thyroxine should be increased to 2 to 2.4 mcg/kg body
weight per day
 A 30% to 50% increase in dosage may be required for women taking

thyroxine before pregnancy
Subclinical Hypothyroidism
Definition:
 TSH (above upper limit of reference range) with normal T4
Often the result of early Hashimoto’s disease
 Risk?
TSH >7.0 mIU/L in the elderly is associated with risk of HF
TSH >10 mIU/L is associated with risk of CHD
Treatment
Rx is controversial because benefits in identified patients are
inconclusive
An association b/n the use of T4 & a reduction in heart disease in
younger pts (40-70 yrs of age) does appear to exist, but not in
older pts (>70 yrs)
Whom to treat ??
TSH between 4.5 and 10 mIU/L &
Symptoms of hypothyroidism
Antithyroid peroxidase antibodies present
History of CV disease, HF, or risk factors for such disease
Initial daily doses of 25-75 mcg recommended - levothyroxine
Myxedema Coma
Severe & life-threatening decompensated hypothyroidism
Mortality rate 30%-60%
 Precipitating causes:
Diseases: trauma, infections, heart failure
Medications: sedatives, narcotics, anesthesia, Li, amiodarone
 Presentation:
 Altered mental state (very common); diastolic hypertension;

hypothermia; hypoventilation
Pharmacotherapy
 IV thyroid hormone replacement
T4: 100-500 µg DL, followed by 75-100 µg/day, until patient can

tolerate oral therapy
Some advocate the use of T3 over T4, given that T3 is more

biologically active & that T4/T3 conversion may be suppressed in
myxedema coma
 Antibiotic therapy: some advocate empiric therapy with broad-

spectrum antibiotics for common infectious causes
 Corticosteroid therapy: hydrocortisone 100 mg TID (or equivalent
steroid)
1. A 43-year-old non-pregnant woman has received a diagnosis of
Graves disease. She is reluctant to try ablative therapy and
wants to try oral pharmacotherapy first. Her thyroid laboratory
values today include TSH 0.22 mIU/L (normal 0.5–4.5 mIU/L)
and free T4 3.2 ng/dL (normal 0.8–1.9 ng/dL). She is anxious
and always feels warm when others say it is too cold. Which is
best for initial treatment of her condition?
A. Lugol’s solution B. Propylthiouracil.
C. Atenolol D. Methimazole
• Answer: D
reluctance to undergo ablative therapy, oral therapy is warranted.
Methimazole is recommended over propylthiouracil because it is

associated with a lower risk of hepatotoxicity,
Answer A is incorrect because iodine therapy is indicated in this

type of case only before surgery or during an acute case of thyroid
storm.
Answer C is incorrect; although β-blockers might provide some

symptomatic relief, they would do little to stabilize this patient’s
thyroid concentrations.
PITUITARY GLAND DISORDERS
Basic Pituitary Gland (Anterior) Hormone Physiology
Classification (focus on the common anterior
pituitary disorders)
• Hypersecretory diseases
Acromegaly and gigantism:
Usually caused by growth hormone (GH)-secreting pituitary adenoma
 Hyperprolactinemia
Most common cause is prolactinomas (prolactin-secreting
pituitary tumor).
 Drug induced (e.g., serotonin reuptake inhibitors and some
antipsychotics)
Central nervous system lesions
Hyposecretory disease
 GH deficiency
 Congenital abnormality caused by GH gene deletion,
GH-releasing hormone deficiency
 Other causes are pituitary aplasia, head trauma, and CNS
infection
 Idiopathic
 Panhypopituitarism
Result of partial or complete loss of anterior and posterior
pituitary function.
Can be caused by primary pituitary tumor, ischemic necrosis of
the pituitary, trauma from surgery, or irradiation
ACTH deficiency, GH deficiency, hypothyroidism, gonadotropin
deficiency
Acromegaly
 Acromegaly results from persistent hypersecretion of growth
hormone (GH).
Excess GH stimulates hepatic secretion of insulin-like growth
factor 1 (IGF-1), which causes the clinical manifestations.
• has a slow onset, and many symptoms do not appear for years.
 Excessive sweating
Osteoarthritis, joint pain, paresthesias, or neuropathies
 Coarsening of facial features
Increased hand volume or ring size, increased shoe size
Hypertension, heart disease, cardiomyopathy
 Sleep apnea
T2D
65
Endocrinologic Disorders
Treatment of Acromegaly
Goals of treatment
Reduce GH and IGF-1 concentrations
 Decrease mortality
Improve clinical symptoms
 Normalize IGF-1 concentrations and suppressed GH concentrations
after OGTT
Treatment
 Treatment of choice is surgical resection of tumor, if causative.
 Pharmacotherapy usually reserved for:

 Control before surgery or irradiation
 When surgery is not possible (usually requires lifelong
pharmacotherapy)
 Surgical failures or relapses after period of remission after
surgery
Dopamine agonists (e.g., bromocriptine, cabergoline)
Dopamine agonist - decrease in GH production
Dosing (bromocriptine is most commonly used agent)
 Initial: 1.25 mg/day by mouth
Maximal: 20–30 mg/day (can titrate once or twice weekly,
as needed)
Adverse effects
 Fatigue, dizziness, nervousness
Diarrhea, abdominal pain
Efficacy:
 Normalization of IGF-1 concentrations in about 10% of patients.
More than 50% of patients experience symptomatic relief
Somatostatin analog (e.g., octreotide)
Blocks GH secretion; 40 times more potent than endogenous
somatostatin
 Initial: 50–100 mcg subcutaneously every 8 hrs or 20 mg orally
twice daily
• Adverse effects
 Diarrhea, nausea, cramps, flatulence, fat malabsorption
Arrhythmias
Hypothyroidism
Biliary tract disorders
Changes in serum glucose concentrations (usually reduces)
GH receptor antagonist (e.g., pegvisomant)
GH derivative binds to liver GH receptors and inhibits IGF-1
Initial: 40 mg once-daily subcutaneous injection loading dose and
then 10 mg once daily
 Maximal: 30 mg/day
Adverse effects
 Nausea, vomiting
 Flulike symptoms
Reversible elevations in hepatic transaminase
• Efficacy: More than 95% of patients attain normal IGF-1
concentrations, and most have improved symptoms.
• A 28-year-old woman presents with acne, facial hair growth, and
irregular menses that have lasted for 6–7months. Her medical history
includes hypertension and depression. Her pituitary and thyroid tests
results have been negative. Her current medications include
amlodipine and fluoxetine. Her prolactin concentration today is 112
ng/mL (normal 15–25 ng/mL). Which is the most likely cause of her
elevated prolactin concentration?
A. Amlodipine B. Prolactin-secreting adenoma.
C. Pregnancy. D. Fluoxetine.
• Answer: D
• Fluoxetine (Answer D), a selective serotonin reuptake inhibitor, can

cause drug-induced hyperprolactinemia.
• Answer A is incorrect because calcium channel blockers are not

associated with an elevated risk of this condition.
• Given the patient’s normal pituitary and thyroid tests, Answer B,

prolactin-secreting adenoma, is probably incorrect.
• Answer C is incorrect because pregnancy is not associated with

an elevated risk of this condition.
Hyperprolactinemia
Causes
Direct: Pituitary tumor (lactotroph adenoma = prolactinoma
accounting for around 40% of tumors)
Indirect: Drug induced (most common nontumor cause), renal
failure, hypothyroidism, breastfeeding
• Potential causative drugs: Typical antipsychotics, opiates, non-
dihydropyridine calcium channel blockers, antidepressants
Diagnosis and clinical presentation
Elevated serum prolactin concentrations; may be challenging to
find specific cause (unless drug induced)
Amenorrhea, anovulation, infertility, hirsutism, and acne in
women
Erectile dysfunction, decreased libido, gynecomastia, and
reduced muscle mass in men
Headache, visual disturbances, bone loss
Treatment Approach
Goal of therapy
 Normalize prolactin concentrations
Normalize gonadotropin secretion
 Relieve symptoms
Decrease tumor size
Therapeutics
• Surgical resection of tumor

 if tumor is very large, causes severe compression of adjacent
tissues,or patient does not respond to pharmacotherapy
• Discontinue causative agent if drug induced.

Recheck prolactin concentration 3 days after discontinuation
Select agent with similar action but no known effect on
prolactin concentrations
 If discontinuation of causative agent not feasible, consider
dopamine agonist
Dopamine agonists (preferred to surgery in most cases)
Cabergoline
preferred agent according to the Endocrine Society guidelines,
long-acting oral agent;
fewer gastrointestinal [GI] adverse effects than bromocriptine
 Initial: 0.5 mg once weekly, Maximal: 4.5 mg/week
Bromocriptine
May restore fertility in more than 90% of women
Long-term cure rates are around 60% for smaller tumors, around
25% for larger tumors.
GH Deficiency
Diagnosis and clinical presentation
Decreased GH concentrations after provocative pharmacologic

challenge (e.g., insulin, clonidine, GH-releasing hormone)
• Clinical presentation
 Delayed growth velocity or short stature
 Central obesity
 Immaturity of the face or prominence of the forehead
Therapy goals
Increase growth velocity
Increase final adult height when treating children
Endocrinologic Disorders
78
Therapeutics: Recombinant GH (somatropin)
Dosing
Depends on which of the various products are selected (dosed
subcutaneously or intramuscularly once daily)
When to discontinue therapy on the basis of growth velocity is
controversial
Once- or twice-monthly long-acting depot formulation is also
available.
Adverse effects
Arthralgia, injection-site pain
Rare but serious cases of idiopathic intracranial hypertension have
been reported.

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Endocrinologic Disorders

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Endocrine Disorders

Pituitary Gland Disorders

Adrenal Gland Disorders

Diabetes Mellitus (Types 1 and 2)

Thyroid hormones affect the function of every organ system

Triiodothyronine (T3) and thyroxine (T4) are the two biologically

 The growth and function of the thyroid are stimulated by activation

 Positive thyroid antibodies indicate an autoimmune thyroid

 Adjuncts to the previous tests include the total T3 (TT3), free T3

 A clinical state caused by inappropriately high thyroid

 Results when tissues are exposed to excessive levels of T4,

 In the United States, the prevalence of hyperthyroidism is

 Toxic diffuse goiter (Graves’ disease):

• Most common hyperthyroid disorder, comprising an estimated 70%

• The incidence of Graves disease is about 0.5 in 1000, with highest

• The incidence in men is 1/5 to 1/10 of that in women.

• Graves disease is rare in children

 Anti-thyrotropin-receptor antibodies also stimulate thyroid

 Usually includes hyperthyroidism, diffuse thyroid enlargement,

Produce excessive TSH secretion that does not respond to normal

Toxic adenoma is the result of autonomous thyroid hormone

A discrete thyroid mass, autonomous, whose function is independent

Several autonomous follicles that, if large enough, cause excessive

 Follicles with autonomous function coexist with normal or even

 Pathogenesis of MNG is thought to be similar to that of toxic

Self-limiting inflammation of the thyroid gland caused by

 Drug induced: excessive exogenous thyroid hormone doses,

Elevated free T4 serum concentrations

Suppressed TSH conce. (except in TSH-secreting adenomas)

If examination and history do not provide the exact etiology,

Radioactive iodine uptake elevated if thyroid gland is actively and

Radioactive iodine uptake is suppressed in disorders caused by

Wt loss with an appetite: cardinal manifestation

Heat intolerance, Goiter, fine hair

Palpitations/tachycardia, nervousness, anxiety, insomnia

Menstrual disturbances (more infrequent menstruation,

Sweating or warm, moist skin

Exophthalmos and pretibial myxedema in Graves’ disease

Minimize or eliminate symptoms

Improve quality of life

Normalize free T4 & TSH concentrations

Minimize long-term damage to organs

 Ablative therapy or Surgical removal of the hyper-secreting

Surgery should be considered in patients with

A large thyroid gland (>80 g),

Severe ophthalmopathy, and

A lack of remission on anti-thyroid drug treatment

Overall morbidity rate with surgery is 2.7%

Most common complications of surgery: hypothyroidism (49%),

PTU or MMI until the patient is biochemically euthyroid (usually 6-8

T4 can be added to maintain the euthyroid state while the

Propranolol for several wks preoperatively & 7-10 days after

 Patients may be discharged if they are asymptomatic and if their

 If iPTH levels are below 10 to 15 pg/mL during the immediate

 Thyroid hormone supplementation (L-thyroxine) should be initiated

 Thyroid hormone supplementation may not be necessary after

 If the TSH is persistently elevated above the normal range,

 Serum calcium levels and calcium and calcitriol supplementation

Initial: 100 mg PO TID

Maximal: 400 mg PO TID