HYPOPITUITARISM

•DR. B. M. SINGH LAMBA

 INTRODUCTION

• It is a clinical syndrome of deficiency in

pituitary hormone production and secretion.
• Panhypopituitarism refers to involvement of
all pituitary hormones; however, it is rare.
• It may result from disorders involving the
pituitary gland, hypothalamus or surrounding
structures.
ANATOMY
PITUITARY
AXES
 ETIOLOGY
• DEVELOPMENTAL/ • NEOPLASTIC
STRUCT URAL – Pituitary adenoma
– Transcription factor defect
– Pituitary dysplasia/aplasia – Parasellar mass
– Congenital Central nervous (germinoma,
system ependymoma, glioma,
mass/encephalocele meningioma, Rathke’s
– Primary empty sella Cyst)
– Congenital hypothalamic – Craniopharyngioma
disorders
– Hypothalamic
• TRAUMATIC
hamartoma,
– Surgical Resection gangliocytom
– Radiation damage a
– Head injuries
– Pituitary
metastases
 ETIOLOGY
• INFILTRATIVE/INFLAM •
MATORY – Pituitary Apoplexy
– Primary hypophysitis
VASCULAR – Pregnancy related
• Lymphocytic – Sickle cell Disease
• Granulomatous
• Xanthomatous
– Arteritis
– Secondary Hypohysitis – Aneurysm
• Sarcoidosis – Diabetes
• Histiocytosis X • INFECTIONS
• Infections – Fungal (histoplasmosis,
• Wegener’s aspergillosis)
granulomatosis
• Takayasu’s disease – Parasitic
– Hemochromatosis (Toxoplasmosis)
– Transcription factor – Tuberculosis
antibodies – Pneumocystis carinii
 ETIOLOGY
• FUNCTIONAL
– Nutritional
– Caloric restriction
– Critical illness – Acute illness, CRF, CLD
– Drugs – Anabolic Steroids, Estrogen, Dopamine,
Thyroxin, GnRH agonists
 CLINICAL FEATURES

• Mass lesions -
– Space occupying lesions result in headache, visual
disturbances and rarely, personality changes,
temporal lobe epilepsy, and CSF rhinorrhoea.
– Actively secreting tumors can produce a complex
picture of combined hormonal excess and deficiency
MASS
LESIO
NS
 CLINICAL FEATURES
• Growth hormone
– Reduced energy and vitality
– Reduced muscle mass and strength
– Increased central adiposity
– Decreased sweating and
impaired thermogenesis
– Reduced bone mineral density
(BMD)
 CLINICAL FEATURES

• Adrenocorticotrophic hormone
–Fatigue, weakness, anorexia, weight loss,
nausea, vomiting, abdominal pain,
hypoglycaemia, circulatory collapse; loss
of axillary/pubic hair in women
 CLINICAL FEATURES

• Gonadotrophins
– Men: erectile dysfunction, reduced muscle mass,
erythropoiesis, reduced energy and vitality
– Women: oligomenorrhoea/amenorrhoea,
dyspareunia, breast atrophy
– Both: loss of libido, flushes, infertility, regression of
sexual characteristics, reduced BMD.
 CLINICAL FEATURES

• Thyroid stimulating hormone

– Fatigue, apathy, cold intolerance, constipation,
weight gain, dry skin, psychomotor retardation.
• Antidiuretic hormone
– Polyuria, polydipsia, nocturia.
• Prolactin
– Lactational failure
• Excessive mortality rates due to cardiovascular
disease
• Order of diminished trophic hormone reserve
function by pituitary compression is
usually :-
– GH>FSH>LH>TSH>ACTH
 INHERITED PITUITARY DEFICIENCY
MUTATION HORMONE DEFICIT
Genetic
Kallmann’s Syndrome FSH, LH
Prader-Willi Syndrome FSH, LH
Lawrence-Moon-Biedl Syndrome FSH, LH
Receptor
GHRH receptor GH
CRH receptor ACTH
GnRH receptor FSH, LH
GPR54 LH, FSH
TRH Receptor TSH
Leptin receptor LH,FSH
Structural
Pituitary Aplasia Any
Pituitary Hypoplasia Any
CNS masses, Encephalocele Any
 INHERITED PITUITARY DEFICIENCY
Transcription Factor Defect
PITX2
PROP1 GH, PRL, TSH, LH, FSH, +/- ACTH
POU1F1(PIT1) PRL, GH, TSH
HESX1 GH, PRL, TSH, LH, FSH, ACTH
LHX3/4 GH, PRL, TSH, LH, FSH
NR0B1 ADRENAL, LH, FSH
TBXI9 (TPIT) ACTH
Hormone Mutation
GH GH
FSHβ FSH
LHβ LH
POMC ACTH
TSHβ TSH
Leptin LH, FSH
Kisspeptin LH,FSH
POU1F1
 LYMPHOCYTIC HYPOPHYSITIS

• Presumed to be autoimmune
• Clinical Presentation
– Women, during postpartum period
– Hyperprolactinemia is seen
– Symptoms of Mass effect with headache & visual
disturbance
– ESR is usually raised
 LYMPHOCYTIC HYPOPHYSITIS

• Deficiency of one or more anterior pituitary hormones

– Diabetes insipidus
• Diagnosis
– MRI - may be indistinguishable from pituitary
adenoma
• Treatment
– Corticosteroids
– Hormone replacement
 PITUITARY APOPLEXY

• Hemorrhagic infarction of a pituitary adenoma/tumor

• Considered a neurosurgical emergency
• Presentation:
– Hypoglycemia
– Hypotension & shock
– CNS hemorrhage
– Severe headache
– Meningismus
– Visual changes
– ophthalmoplegia
 PITUITARY APOPLEXY

• Risk factors:
– Diabetes
– Radiation treatment
– Warfarin use
• Symptoms may occur immediately or may develop over
1-2 days
• Diagnose with CT/MRI
• Treatment:
– Surgical – Trans-sphenoid decompression
– Medical therapy – if symptoms are mild
• Corticosteroids
 Pituitary Apoplexy
Radiology
 SHEEHAN’S SYNDROME

• Named after British Pathologist, Harold Leeming

Sheehan, who described specific association with
PPH
• Ischemic pituitary necrosis after substantial blood
loss during childbirth
 SHEEHAN’S SYNDROME

• No correlation between severity of hemorrhage

and symptoms
• Recognised days to weeks post-partum
– Secondary hypothyroidism
– Lactational Failure
– Secondary Adrenal insufficiency - Lethargy, anorexia,
weight loss
– Typically long interval between obstetric event and
diagnosis
 HEAD TRAUMA
• PARTIALLY OR TOTALLY DAMAGED BY BIRTH
TRAUMA, CRANIAL HEMORHHAGE, FETAL
ASPHYXIA, OR BREECH DELIVERY
• HEAD TRAUMA MAY LEAD TO SELLA
TURCICA FRACTURE, PITUITARY STALK
SECTION, TRAUMA INDUCED VASOSPASM,
OR ISCHEMIC INFARCTION
 HEAD TRAUMA
• Most common traumatic cause is iatrogenic
neurosurgical trauma
• Transient or permanent diabetes insipidus and
varying degrees of anterior pituitary
dysfunction
• Hypopituitarism usually manifests within a year
after the insult
 RADIATION INJURY

• Causes atrophy of the pituitary gland along

with damage to hypothalamic synthesis of
hypophysiotropic hormones
• Radiation dose exposure, time interval after
completion of radiotherapy, & distance of
pituitary from central energy field correlate
with development of pituitary hormone
deficits
 RADIATION INJURY

• Pattern of loss – GH>FSH/LH>ACTH>TSH

• Previously irradiated patients should undergo
lifelong periodic anterior pituitary hormone
testing
 EMPTY SELLA SYNDROME
Often an incidental MRI finding
 EMPTY SELLA SYNDROME

• Usually have normal pituitary function

– Implying that the surrounding rim of pituitary
tissue is fully functional

• Hypopituitarism may develop insidiously when >90%

tissue is compressed.
 EMPTY SELLA SYNDROME

• Primary empty sella may develop as a consequence of

congenital weakness of the diaphragm

• Pituitary masses may undergo clinically silent

infarction with secondary development of a partial or
totally empty sella by cerebrospinal fluid (CSF)
filling the dural herniation.

• Rarely, functional pituitary adenomas may arise within

the rim of pituitary tissue, and these are not always
visible on MRI
 DIAGNOSIS
• Thorough clinical examination including visual
field charting is essential
• Simultaneous measurements of basal anterior
pituitary and target organ hormone levels
• Dynamic/provocative tests are necessary to
assess GH secretory reserve and ACTH-adrenal
axis
HORMONE TEST BLOOD SAMPLE INTERPRETATION
Growth INSULIN TOLERANCE TEST – regular -30, 0, 30, 60, 120 Glucose<40, GH should
Hormone insulin(0.05-0.15 U/kg iv) min for glucose be >3ug/dl
and GH

GHRH TEST – 1 ug/kg iv 0, 15, 30, 45, 60, Normal response is

120 min for GH GH>3 ug/dl

L-ARGININE TEST – 30 g iv over 30 min 0, 30, 60, 120 min Normal response is
for GH GH>3 ug/dl

L-DOPA TEST – 500 mg PO 0, 30, 60, 120 min Normal response is

for GH GH>3 ug/dl
 HORMONE TEST BLOOD SAMPLE INTERPRETATION
Prolactin TRH TEST – 200-500 ug iv 0, 20 and 60 min Normal PRL >2 ug/L and
for TSH and PRL increase >200% of
baseline

TSH BASAL THYROID FUNCTION TESTS – T3, Basal Low free thyroid
T4, TSH measurements hormone with
normal/low TSH

TRH TEST – 200-500 ug IV 0, 20, 60 min for TSH should increase by

TSH and PRL >5 mIU/L unless thyroid
hormone levels are
increased
HORMONE TEST BLOOD SAMPLE INTERPRETATION
ACTH INSULIN TOLERANCE TEST – regular -30, 0, 30, 60, 120 Glucose<40, Cortisol
insulin(0.05-0.15 U/kg iv) min for glucose should increase by
and cortisol >7ug/dl or to >20
ug/dl
CRH TEST– 1 ug/kg iv at 8 AM 0, 15, 30, 45, 60, Basal ACTH increases 2-
90, 120 min for to 4-fold & peaks at 20-
ACTH & cortisol 100 pg/ml. Cortisol >20-
25 ug/dl

METYRAPONE TEST– 30mg/kg at Plasma 11- Plasma cortisol should

midnight deoxycortisol and be <4 ug/dl to assure an
cortisol at 8 AM; adequate response.
ACTH can also be Normal response is 11-
measured deoxycortisol >7.5 ug/dl
or ACTH >75 pg/ml

STANDARD ACTH STIMULATION TEST – 0, 30, 60 min for Cortisol > 21 ug/dl &
Cosyntropin 0.25 mg im or iv cortisol and aldosterone > 4ng/dL
aldosterone above baseline

LOW DOSE ACTH TEST – 1 ug iv 0, 30, 60 min for Cortisol > 21 ug/dL
cortisol

3-DAY ACTH STIMULATION TEST – 0.25 Cortisol > 21 ug/dL

mg cosyntropin iv over 8 h each day
 HORMONE TEST BLOOD SAMPLE INTERPRETATION
LH, FSH LH, FSH, TESTOSTERONE, ESTROGEN Basal Basal LH & FSH should
measurements be increased in
postmenopausal women
Low testosterone levels
with low FSH & LH
indicate pituitary
insufficiency

LH should increase by 10
GnRH TEST – 100 ug iv 0, 30, 60 min for IU/L and FSH by 2 IU/L
LH & FSH Normal responses are
variable

Multiple COMBINED ANTERIOR PITUITARY TESTS: -30, 0, 15, 30, 60, Combined or individual
hormones GHRH (1ug/kg), CRH (1 ug/kg), GnRH 90, 120 min for releasing hormone
(100 ug), TRH (200 ug) are given iv GH, ACTH, responses must be
cortisol, LH, FSH, elevated in the context
and TSH of basal target gland
hormone values
 TREATMENT
• Hormone replacement therapy
• It should mimic physiological hormone
production
• Those with glucocorticoid replacement
require dose adjustments during stressful
events like acute illness, pregnancy, surgery,
dental procedures, trauma, and acute
hospitalization
 TSH DEFICIENCY

• Thyroxine is the treatment of choice.

• ACTH deficiency should be treated if present
before initiating thyroxine replacement.
• TSH monitoring is unhelpful
• Long term over treatment may result in AF &
reduction in bone mineral density
 GONADOTROPHIN DEFICIENCY

MEN
• Testosterone replacement has beneficial
effects on body composition, sexual function,
mood, behavior & BMD.
• Treatment is contraindicated in patients with
prostate cancer and male breast cancer
 GONADOTROPHIN DEFICIENCY

WOMEN
• Oestrogen replacement alleviates
symptoms of deficiency and is bone
protective.
• It is often given with cyclical/continuous
progesterone.
 GH DEFICIENCY

• Human GH 0.2-0.3 mg s.c. is given daily,

titrating the dose every 4-6 weeks
• Side effects include headache, arthralgia,
myalgia, fluid retention.
• Absolute contraindications are active
malignancy, benign intracranial hypertension
and proliferative diabetic retinopathy
 VASOPRESSIN DEFICIENCY

• In mild Diabetes Insipidus, (urine output

<4l/day), adequate oral fluid intake is
sufficient
• In severe forms desmopressin is the treatment
of choice
• Hyponatremia is a common side effect
 ACTH DEFICIENCY

• Hydrocortisone is the preferred agent

• 2 to 3-fold increase in glucocorticoid dose is
needed temporarily during intercurrent
illness, surgery, etc.
 TROPHIC HORMONE DEFICIT HORMONE REPLACEMENT
ACTH Hydrocortisone (10-20 mg A.M. ; 5-10 mg P.M.)
Cortisone acetate (25 mg A.M. ; 12.5 mg P.M.)
Prednisone (5 mg A.M.)

TSH L-Thyroxine (0.075-0.15 mg daily)

FSH/LH MALES
Testosterone enanthate (200 mg IM every 2 weeks)
Testosterone skin patch (5 mg/day)
FEMALES
Conjugated estrogen (0.65-1.25 mg qd for 25 days)
Progesterone (5-10 mg qd) on days 16-25
Estradiol skin patch (0.5 mg, every other day)
FOR FERTILITY – menopausal gonadotropins, human
chorionic gonadotropins

GH ADULTS – Somatotropin (0.1-1.25 mg SC qd)

CHILDREN – Somatotropin (0.02-0.05 mg/kg/day)
VASOPRESSIN Intranasal Desmopressin (5-20 ug twice daily)
Oral 300-600 ug qd
THANK
YOU