Pituitary Disorders
Medicine · Endocrinology · lean revision notes
Pituitary Disorders
The pituitary is the "master gland" sitting in the sella turcica, anatomically wedged below the optic chiasma and within the cavernous sinus. Disorders arise from hormone excess (functioning adenomas), hormone deficiency (hypopituitarism, Sheehan syndrome) or mass effect (visual field loss, headache). For NEET PG, the recurring favourites are acromegaly, prolactinoma, Sheehan syndrome and diabetes insipidus — each with a signature investigation and a signature drug.
Anatomy & physiology you must own
The gland has two embryologically distinct lobes:
- Anterior pituitary (adenohypophysis) — from Rathke's pouch (oral ectoderm). Secretes GH, prolactin, ACTH, TSH, LH, FSH. Controlled by hypothalamic releasing/inhibiting hormones reaching it via the hypophyseal portal system.
- Posterior pituitary (neurohypophysis) — neural ectoderm. Stores and releases ADH (vasopressin) and oxytocin, synthesised in the supraoptic and paraventricular nuclei.
High-yield: Prolactin is the only anterior pituitary hormone under predominantly inhibitory control (dopamine from the hypothalamus). Hence anything that cuts the stalk (stalk effect) or blocks dopamine raises prolactin while lowering every other anterior hormone.
The optic chiasma lies directly above the sella; suprasellar extension of a tumour classically compresses the crossing fibres from the nasal retinae → bitemporal hemianopia (upper quadrants first, as inferior chiasmal fibres are hit earliest).
Classification of pituitary adenomas
| Basis | Categories |
|---|---|
| Size | Microadenoma < 10 mm; Macroadenoma ≥ 10 mm |
| Function | Functioning (secretory) vs Non-functioning |
| Commonest functioning tumour | Prolactinoma (~40–50%) |
| Commonest in autopsy/incidentaloma | Non-functioning |
| Hormone secreted (frequency) | Prolactin > GH > ACTH > TSH (rare) |
High-yield: The single most common pituitary adenoma overall is the prolactinoma. The most common cause of bitemporal hemianopia is a non-functioning macroadenoma (it presents late, by mass effect, since it secretes nothing detectable).
Acromegaly (GH excess)
Caused in >95% by a GH-secreting somatotroph adenoma. If GH excess occurs before epiphyseal fusion → gigantism; after fusion → acromegaly. GH acts largely via hepatic IGF-1 (somatomedin C).
Clinical features
- Acral enlargement — large hands/feet (ring/shoe size increases), frontal bossing, prognathism, macroglossia, widely spaced teeth.
- Soft-tissue: doughy handshake, skin tags, oily skin, sweating.
- Carpal tunnel syndrome, arthropathy, obstructive sleep apnoea.
- Organomegaly, cardiomyopathy (commonest cause of death — cardiovascular), hypertension.
- Impaired glucose tolerance / diabetes (GH is anti-insulin, diabetogenic).
- Colonic polyps → increased colorectal carcinoma risk (screen with colonoscopy).
Diagnosis — stepwise
1. Screen: serum IGF-1 (best single screening test — reflects integrated 24-h GH, no diurnal swing) → 2. Confirm: Oral Glucose Tolerance Test (OGTT) with GH measurement → 3. Localise: pituitary MRI with contrast → 4. Assess complications (echo, colonoscopy, visual fields, glucose).
High-yield: The confirmatory / gold-standard test for acromegaly is failure of GH suppression after a 75 g oral glucose load. In normals GH falls to < 1 ng/mL (< 0.4 ng/mL on ultrasensitive assays); in acromegaly it stays high or paradoxically rises. Random GH is useless (pulsatile).
| Test | Role | Key cut-off |
|---|---|---|
| Serum IGF-1 | Screening | Elevated for age/sex |
| 75 g OGTT + GH | Confirmation | GH not suppressed < 1 ng/mL |
| Pituitary MRI (contrast) | Localisation | Microadenoma vs macroadenoma |
| Random GH | Not useful | Pulsatile, unreliable |
Management
Trans-sphenoidal surgery (TSS) is the first-line / treatment of choice for resectable tumours. Adjunctive:
- Somatostatin analogues — octreotide, lanreotide (medical DOC when surgery fails or pre-op for macroadenomas).
- Pegvisomant — GH-receptor antagonist (normalises IGF-1 when others fail; does not shrink tumour).
- Cabergoline (dopamine agonist) — modest effect, useful if mild/co-secreting prolactin.
- Radiotherapy — last line for residual disease.
High-yield: Mnemonic for acromegaly complications — "ACROMEGALY": Arthralgia/Acral, Carpal tunnel, Ring/shoe size up, Organomegaly, Macroglossia, Enlarged jaw (prognathism), Glucose intolerance, Apnoea (sleep), Lipodystrophy/sweating, Y = hYpertension/heart disease (the killer).
Prolactinoma & Hyperprolactinaemia
Most common functioning adenoma. In women presents early (small microadenomas) with the amenorrhoea–galactorrhoea syndrome; in men presents late (macroadenoma, mass effect) with erectile dysfunction, decreased libido, gynaecomastia.
Causes of raised prolactin (differentials)
- Physiological: pregnancy, lactation, stress, sleep, nipple stimulation.
- Pathological: prolactinoma, stalk compression (any sellar mass disconnecting dopamine), primary hypothyroidism (high TRH stimulates prolactin), chronic kidney disease, cirrhosis, PCOS.
- Drugs: dopamine antagonists — metoclopramide, domperidone, antipsychotics (risperidone, haloperidone), methyldopa, verapamil, oestrogens, opioids.
High-yield: A prolactin level > 200 ng/mL strongly suggests a prolactinoma. A large pituitary mass with only mildly raised prolactin (< 100–150 ng/mL) suggests a non-functioning adenoma causing stalk effect, not a prolactinoma. Beware the hook effect: a very large prolactinoma can give a falsely low reading due to assay saturation — dilute the sample if clinically suspicious.
Management — note the exception!
High-yield: Prolactinoma is the one pituitary tumour where MEDICAL therapy, not surgery, is first-line. Dopamine agonists — cabergoline (preferred, twice weekly, better tolerated) or bromocriptine — shrink the tumour and normalise prolactin. Bromocriptine is preferred in pregnancy/fertility planning (longest safety record).
Surgery (TSS) is reserved for dopamine-agonist resistance/intolerance, apoplexy, or CSF leak.
Hypopituitarism & Sheehan Syndrome
Deficiency of one or more anterior pituitary hormones. Order of hormone loss with progressive compression follows the mnemonic "Go Look For The Adenoma" — GH → LH/FSH (gonadotropins) → TSH → ACTH lost last (and prolactin may rise from stalk effect).
| Axis lost | Clinical effect |
|---|---|
| GH | Children: short stature; Adults: ↓ muscle/↑ fat, fatigue |
| LH/FSH | Amenorrhoea, infertility, loss of libido, ↓ body hair |
| TSH | Central hypothyroidism (low T4, low/normal TSH) |
| ACTH | Secondary adrenal insufficiency — the life-threatening loss |
Sheehan syndrome
Postpartum ischaemic necrosis of the (enlarged) pituitary following severe obstetric haemorrhage and hypotension. The pituitary doubles in size in pregnancy (lactotroph hyperplasia) without a matching rise in blood supply, making it exquisitely vulnerable to hypoperfusion.
- Earliest sign: failure of postpartum lactation (prolactin deficiency).
- Followed by failure to resume menses, loss of axillary/pubic hair, fatigue, features of hypothyroidism and adrenal insufficiency.
- Can present acutely with postpartum hypoglycaemia/hypotension or insidiously years later.
High-yield: First and most sensitive feature of Sheehan syndrome = inability to lactate. The dangerous deficiency is ACTH → cortisol; replace glucocorticoids BEFORE thyroxine in any panhypopituitarism — giving thyroxine first accelerates cortisol metabolism and can precipitate adrenal crisis.
Pituitary apoplexy = sudden haemorrhage/infarction into an adenoma → thunderclap headache, ophthalmoplegia, visual loss, acute hypopituitarism — an endocrine emergency needing IV hydrocortisone and urgent imaging.
Dynamic testing of pituitary reserve
- GH reserve — provocative testing with insulin tolerance test (ITT) is the gold standard: insulin-induced hypoglycaemia (< 40 mg/dL) should provoke a GH and cortisol surge; a flat response confirms deficiency. Glucagon stimulation is a safer alternative where ITT is contraindicated (epilepsy, ischaemic heart disease).
- ACTH–cortisol axis — 8 am serum cortisol; if equivocal, short Synacthen (ACTH stimulation) test or ITT.
- Gonadotropins — basal LH/FSH with testosterone/oestradiol; low sex steroid with low/inappropriately normal LH/FSH localises the defect to the pituitary/hypothalamus (hypogonadotropic hypogonadism).
High-yield: A low target-gland hormone with a low or inappropriately normal trophic (pituitary) hormone = central/secondary failure; a low target hormone with a high trophic hormone = primary gland failure. This pattern recognition repeatedly distinguishes pituitary from end-organ disease in MCQ stems.
Empty sella syndrome
Herniation of the subarachnoid space into the sella flattens the gland against the floor. Primary empty sella (defect in the diaphragma sellae, often obese multiparous women) is usually an incidental finding with normal function; secondary empty sella follows surgery, radiotherapy, infarction (including Sheehan) or apoplexy and may cause hypopituitarism.
Diabetes Insipidus (DI)
A disorder of water balance: deficiency of ADH (central) or renal resistance to ADH (nephrogenic), producing large volumes of dilute, hypotonic urine, polyuria (> 3 L/day) and compensatory polydipsia.
| Feature | Central DI | Nephrogenic DI |
|---|---|---|
| Defect | ↓ ADH secretion | Renal ADH resistance |
| Causes | Idiopathic, trauma/surgery, tumour, Sheehan, granuloma | Lithium, hypercalcaemia, hypokalaemia, hereditary (V2 receptor/AQP2), chronic renal disease |
| Plasma ADH | Low | Normal/high |
| Response to desmopressin (DDAVP) | Urine concentrates (> 50% rise in osmolality) | No / minimal response |
| Treatment | Desmopressin | Treat cause; thiazides, amiloride, low-salt diet, NSAIDs |
Diagnostic approach — stepwise
1. Confirm hypotonic polyuria (urine osmolality low despite high/normal serum osmolality) → 2. Water deprivation test → 3. Administer desmopressin (DDAVP) to differentiate central vs nephrogenic.
High-yield: In the water deprivation test, normal subjects concentrate urine; in DI urine stays dilute. After giving DDAVP, central DI urine osmolality rises (> 50%) while nephrogenic DI shows little/no rise. Serum copeptin (ADH surrogate) is the newer confirmatory marker.
Key differential — primary polydipsia (psychogenic): also polyuria, but here the patient over-drinks; serum sodium/osmolality tends to be low-normal (vs high-normal in true DI), and the water deprivation test concentrates urine appropriately.
High-yield: Lithium is the classic drug cause of nephrogenic DI. Treatment paradox: thiazide diuretics reduce urine output in nephrogenic DI (induce mild volume depletion → enhanced proximal reabsorption). Amiloride is specifically used for lithium-induced nephrogenic DI (blocks ENaC lithium entry).
SIADH — the mirror image
The opposite of central DI: excess ADH → water retention, dilutional hyponatraemia, concentrated urine, low serum osmolality, euvolaemia. Causes: small-cell lung carcinoma, CNS disease, pneumonia, drugs (carbamazepine, SSRIs). Treat with fluid restriction; tolvaptan (V2 antagonist) or demeclocycline in refractory cases. Often paired against DI in MCQs.
Approach to a sellar mass (integration)
Headache + bitemporal hemianopia → suspect pituitary macroadenoma → MRI sella with contrast (investigation of choice) → full anterior pituitary hormone panel (prolactin, IGF-1, 8 am cortisol/ACTH, free T4/TSH, LH/FSH, testosterone/oestradiol) → identify secretory vs non-functioning → treat (dopamine agonist if prolactinoma, else trans-sphenoidal surgery).
High-yield: MRI with gadolinium is the imaging investigation of choice for any pituitary lesion (CT only if MRI contraindicated, though CT better shows bony sella/calcification e.g. craniopharyngioma).
Craniopharyngioma — key paediatric/suprasellar differential: derived from Rathke's pouch remnants, classically calcified, cystic ("machinery-oil" / motor-oil fluid rich in cholesterol), causes growth failure + DI + visual loss in children. Adamantinomatous histology in kids.
Recently asked / exam angle
- Confirmatory test for acromegaly = GH non-suppression on 75 g OGTT (screening = IGF-1). Repeatedly tested as a one-liner.
- First-line treatment of prolactinoma = dopamine agonist (cabergoline), NOT surgery — the favourite "exception" MCQ.
- Earliest feature of Sheehan syndrome = failure of lactation; "postpartum haemorrhage + no lactation + amenorrhoea" stem.
- Replace steroid before thyroxine in panhypopituitarism — a classic management trap.
- Water deprivation test + DDAVP response to separate central from nephrogenic DI; lithium as the drug cause of nephrogenic DI; thiazide/amiloride as treatment.
- Bitemporal hemianopia — anatomy of optic chiasma compression, upper quadrants first.
- Hook effect in massive prolactinomas giving falsely low prolactin — increasingly tested.
- Acromegaly commonest cause of death = cardiovascular; screen for colorectal cancer.
- Most common pituitary tumour = prolactinoma; most common causing mass effect = non-functioning macroadenoma.
- Copeptin as a modern surrogate for ADH in DI workup.
Rapid revision
- Prolactinoma = commonest pituitary adenoma; treat with cabergoline/bromocriptine first, surgery only if resistant.
- Prolactin is the only anterior hormone under inhibitory (dopamine) control → stalk lesions raise it, lower the rest.
- Acromegaly screen = IGF-1; confirm = GH non-suppression on OGTT (< 1 ng/mL is normal); localise = MRI; DOC = trans-sphenoidal surgery.
- Acromegaly medical DOC = octreotide/lanreotide; pegvisomant = GH-receptor antagonist; death usually cardiovascular.
- Sheehan syndrome = postpartum pituitary necrosis after PPH; earliest sign = failure to lactate.
- In panhypopituitarism give hydrocortisone before levothyroxine to avoid adrenal crisis.
- Pituitary apoplexy = sudden headache + visual loss + ophthalmoplegia → IV hydrocortisone, urgent MRI.
- Central DI responds to DDAVP (urine concentrates); nephrogenic DI does not.
- Lithium is the classic cause of nephrogenic DI; treat with thiazides/amiloride.
- SIADH = mirror of DI → euvolaemic hyponatraemia, concentrated urine; treat with fluid restriction/tolvaptan.
- Bitemporal hemianopia = optic chiasma compression by a macroadenoma; MRI sella with contrast is the imaging of choice.
- Craniopharyngioma = calcified cystic suprasellar Rathke's pouch tumour with "machinery-oil" fluid in children.