Pituitary Pathology

The pituitary is a high-yield CNS–endocrine crossover zone for NEET PG, blending histopathology, radiology, and clinical endocrinology. This set covers adenoma classification, acromegaly, craniopharyngioma, Sheehan syndrome, and diabetes insipidus — with the favourite buzzwords (machine-oil fluid, cholesterol crystals, bitemporal hemianopia) flagged throughout.

Normal anatomy and histology — the foundation

The pituitary (hypophysis) sits in the sella turcica of the sphenoid bone, connected to the hypothalamus by the infundibulum (pituitary stalk). It has two embryologically and functionally distinct parts:

Feature	Anterior pituitary (Adenohypophysis)	Posterior pituitary (Neurohypophysis)
Embryological origin	Rathke's pouch (oral ectoderm / stomodeum)	Neuroectoderm (downgrowth of diencephalon)
Cell type	Epithelial secretory cells	Axons of hypothalamic neurons (no true gland)
Blood supply	Hypophyseal portal system (no direct arterial)	Inferior hypophyseal artery (direct)
Hormones	GH, PRL, ACTH, TSH, FSH, LH	ADH (vasopressin), oxytocin — stored, not made here
Hormone synthesis site	Anterior pituitary itself	Supraoptic & paraventricular nuclei (hypothalamus)

On H&E, anterior pituitary cells are classically divided by staining:

• Acidophils (40%) → GH (somatotrophs) and PRL (lactotrophs)
• Basophils (10%) → ACTH (corticotrophs), TSH (thyrotrophs), FSH/LH (gonadotrophs). Mnemonic for basophils: "B-FLAT" = Basophil → FSH, LH, ACTH, TSH.
• Chromophobes (50%) → degranulated/resting cells

High-yield: Rathke's pouch (oral ectoderm) gives the anterior pituitary AND craniopharyngioma; the posterior pituitary is neuroectodermal. This single fact answers a cluster of NEET PG embryology + pathology items.

Pituitary adenoma — classification

Pituitary adenomas are the most common cause of hyperpituitarism and account for ~10–15% of intracranial neoplasms. They are benign monoclonal proliferations of anterior pituitary cells.

Size-based classification

• Microadenoma → < 1 cm
• Macroadenoma → ≥ 1 cm (mass effect, hypopituitarism)

Functional classification by cell type

Adenoma type	Hormone	Frequency	Clinical syndrome
Prolactinoma (lactotroph)	Prolactin	Most common (~30%)	Amenorrhoea, galactorrhoea, ↓libido, infertility
Somatotroph	GH	2nd–3rd	Gigantism (children), acromegaly (adults)
Corticotroph	ACTH		Cushing disease; Nelson syndrome post-adrenalectomy
Gonadotroph	FSH/LH		Often "silent", hypogonadism, mass effect
Thyrotroph	TSH	Rarest	Central hyperthyroidism
Null cell	None		Mass effect / hypopituitarism only

High-yield: Prolactinoma is the single most common functioning pituitary adenoma. Overall, the most common adenoma in surgical/autopsy series may be reported as non-functioning (null-cell/gonadotroph), but among functioning tumours, prolactinoma dominates — read the stem carefully.

Pathology pearls

• Adenomas are typically monomorphic (uniform cells) with loss of the normal acinar reticulin network — reticulin stain loss is a key diagnostic feature distinguishing adenoma from hyperplasia.
• Pituitary apoplexy = acute haemorrhage/infarction into an adenoma → sudden headache, ophthalmoplegia, visual loss, collapse. A neurosurgical emergency.
• GH adenomas may show fibrous bodies (keratin) on EM; ACTH adenomas can show Crooke's hyaline change in non-tumorous corticotrophs (from high cortisol).

Mass effect (any macroadenoma)

Suprasellar extension compresses the optic chiasm → bitemporal hemianopia (classic). Other effects: headache, hypopituitarism (compression of normal gland), cranial nerve palsies (cavernous sinus → III, IV, VI, V1, V2), and rarely CSF rhinorrhoea.

Flow of mass effect: Adenoma grows → compresses normal pituitary (hypopituitarism) → extends superiorly → compresses optic chiasm → bitemporal hemianopia → lateral extension → cavernous sinus cranial nerve palsies.

Prolactinoma — clinical and management

Hyperprolactinaemia inhibits GnRH pulsatility → hypogonadism.

• Women: amenorrhoea, galactorrhoea, infertility (present early, usually microadenoma).
• Men: decreased libido, erectile dysfunction, often present late as macroadenoma with mass effect.

High-yield: Stalk effect — any large non-prolactin sellar mass that compresses the stalk causes mild–moderate hyperprolactinaemia (loss of dopamine inhibition). Serum prolactin > 200 ng/mL strongly favours a true prolactinoma; modest elevation (< 100–150) may be stalk effect.

Drug of choice: Dopamine agonists — cabergoline (1st line) or bromocriptine. Medical therapy shrinks prolactinomas, so surgery is rarely first-line. (Contrast: nearly all other adenomas are managed by trans-sphenoidal surgery first.)

Acromegaly and gigantism

Caused by a GH-secreting somatotroph adenoma (>95% of cases). Excess GH → hepatic IGF-1 (somatomedin C) which mediates most effects.

• Before epiphyseal fusion (children) → gigantism (proportional tall stature).
• After fusion (adults) → acromegaly (acral/soft-tissue overgrowth).

Clinical features

• Coarse facial features, frontal bossing, prognathism, macroglossia, widely spaced teeth.
• Enlarged hands/feet (ring/shoe size ↑), soft-tissue swelling.
• Carpal tunnel syndrome, skin tags, oily skin, hyperhidrosis.
• Organomegaly (cardiomegaly → cardiomyopathy is the leading cause of death), colonic polyps (↑colorectal cancer risk).
• Metabolic: impaired glucose tolerance / diabetes mellitus (GH is diabetogenic), hypertension.

Diagnosis — investigation of choice

1. Screening: Serum IGF-1 (elevated; not pulsatile, so a reliable single value). Random GH is unreliable (pulsatile).
2. Confirmation (gold standard): Oral Glucose Tolerance Test (OGTT) — give 75 g glucose; in normals GH suppresses to < 1 ng/mL. Failure of GH to suppress confirms acromegaly.
3. Localisation: MRI of the sella with contrast.

High-yield: Acromegaly confirmation = failure of GH suppression after 75 g oral glucose (OGTT). IGF-1 is the best screening test. Memorise both.

Management

• Trans-sphenoidal surgery = treatment of choice.
• Medical (if surgery fails): Somatostatin analogues (octreotide, lanreotide) — drug of choice medically; pegvisomant (GH receptor antagonist); cabergoline (adjunct).
• Radiotherapy reserved for refractory cases.

Craniopharyngioma — the favourite crossover tumour

A benign (WHO grade 1) but locally aggressive suprasellar tumour arising from remnants of Rathke's pouch (squamous epithelial rests along the pituitary stalk).

High-yield: Craniopharyngioma = Rathke's pouch origin. This is the most repeated NEET PG craniopharyngioma fact, alongside the gross "machine oil" fluid and microscopic cholesterol crystals.

Epidemiology — bimodal age

• Children (5–15 yrs): adamantinomatous type (more common overall, classic).
• Adults (>50 yrs): papillary type.

Gross & microscopic pathology

Feature	Adamantinomatous (children)	Papillary (adults)
Cyst fluid	"Machine oil" / motor-oil brownish-yellow fluid rich in cholesterol crystals	Usually solid, fewer cysts
Microscopy	Palisading squamous epithelium, "wet keratin" / stellate reticulum, calcification	Squamous epithelium, no wet keratin, no calcification
Calcification on imaging	Common (~90%)	Rare
BRAF V600E mutation	Absent	Present
CTNNB1 (β-catenin) mutation	Present	Absent

High-yield: The dark brownish-yellow "machine-oil/crankcase-oil" cyst fluid glittering with cholesterol crystals and calcification on CT = adamantinomatous craniopharyngioma in a child. Memorise the triad: machine oil fluid + cholesterol clefts + wet keratin + calcification.

Clinical features

• Children: growth failure (GH deficiency), visual disturbance, raised ICP (headache, vomiting), bitemporal hemianopia (suprasellar compression of chiasm).
• Diabetes insipidus if hypothalamic/posterior pituitary involvement.
• The most common childhood suprasellar tumour and the most common cause of hypopituitarism in children.

Investigation of choice: MRI (extent, cystic/solid) + CT (best to show calcification). Definitive diagnosis is histopathological. Management: Surgical resection ± radiotherapy; recurrence is common due to adherence to vital structures.

Sheehan syndrome (postpartum pituitary necrosis)

Ischaemic necrosis of the anterior pituitary caused by postpartum haemorrhage and hypotension.

Pathophysiology

During pregnancy the anterior pituitary physiologically enlarges (lactotroph hyperplasia) but its blood supply (low-pressure portal system) does not increase proportionally. Severe postpartum haemorrhage → hypovolaemic shock → infarction of the enlarged, vulnerable gland. The posterior pituitary is usually spared (direct arterial supply).

Clinical features — onset can be acute or insidious (years later)

• Failure of lactation (↓prolactin) — often the earliest clue.
• Failure to resume menses (↓FSH/LH), loss of pubic/axillary hair.
• Fatigue, cold intolerance (↓TSH → secondary hypothyroidism).
• Adrenal insufficiency (↓ACTH) → hypotension, hyponatraemia — can be life-threatening.

High-yield: A postpartum woman with PPH who fails to lactate and does not resume menses = Sheehan syndrome. It is panhypopituitarism; ADH (posterior) is typically preserved, so overt DI is uncommon.

Mnemonic for anterior hormone loss order (Sheehan / compression): "Go Look For The Adenoma's Problem" loosely — practically, GH and gonadotrophins (FSH/LH) are lost earliest, ACTH and TSH later.

Diabetes insipidus (posterior pituitary / ADH disorder)

DI = inability to concentrate urine due to ADH deficiency or resistance → polyuria + polydipsia with dilute urine.

Feature	Central (neurogenic) DI	Nephrogenic DI
Defect	↓ADH production/release	Renal resistance to ADH
Causes	Tumour, surgery, trauma, craniopharyngioma, infiltration (Langerhans cell histiocytosis), Sheehan (rare)	Lithium, hypercalcaemia, hypokalaemia, hereditary (V2 receptor/AQP2)
Serum osmolality	High	High
Urine osmolality	Low (dilute)	Low (dilute)
Response to desmopressin (water deprivation test)	Urine osmolality RISES (>50%)	No significant rise
Treatment	Desmopressin (DDAVP)	Treat cause; thiazides, low-salt diet, NSAIDs (amiloride for lithium)

Diagnostic flow: Polyuria → exclude DM (glucose) → water deprivation test → urine stays dilute (confirms DI) → give desmopressin → urine concentrates = central DI; no response = nephrogenic DI.

High-yield: Water deprivation test + desmopressin challenge distinguishes central from nephrogenic DI. Central responds to DDAVP; nephrogenic does not. Contrast with SIADH (opposite picture: concentrated urine, hyponatraemia, euvolaemia).

Hypopituitarism — additional causes

• Mass lesions (adenoma, craniopharyngioma, metastasis)
• Sheehan syndrome, pituitary apoplexy
• Empty sella syndrome (CSF herniates into sella, flattens gland; often asymptomatic / mild)
• Iatrogenic (surgery, radiation), infiltrative (sarcoidosis, Langerhans cell histiocytosis, haemochromatosis), lymphocytic hypophysitis (autoimmune, postpartum, mimics adenoma)

Key differentials at a glance

• Suprasellar mass in a child → craniopharyngioma (calcified, cystic) vs pilocytic astrocytoma vs germinoma vs Rathke cleft cyst.
• Rathke cleft cyst vs craniopharyngioma: cleft cyst is a benign non-neoplastic remnant lined by ciliated/cuboidal epithelium, no wet keratin, no robust calcification, no machine-oil fluid.
• Hyperprolactinaemia: true prolactinoma vs stalk effect vs drugs (antipsychotics, metoclopramide) vs pregnancy vs hypothyroidism.
• Polyuria: DI vs DM vs primary polydipsia (psychogenic — low serum osmolality, distinguishes it).

Recently asked / exam angle

• Craniopharyngioma originates from Rathke's pouch — repeatedly tested embryology link.
• "Machine-oil" cyst fluid + cholesterol crystals + calcification → identify adamantinomatous craniopharyngioma.
• OGTT (failure of GH suppression) as the confirmatory test for acromegaly; IGF-1 for screening.
• Most common functioning pituitary adenoma = prolactinoma; DOC = cabergoline.
• Bitemporal hemianopia mechanism (optic chiasm compression) — neuroanatomy crossover.
• Sheehan syndrome: failure to lactate post-PPH; posterior pituitary spared.
• Water-deprivation/desmopressin differentiation of central vs nephrogenic DI; lithium → nephrogenic DI.
• Crooke's hyaline change (Cushing/ACTH excess) and reticulin stain loss (adenoma vs hyperplasia) as pathology one-liners.
• BRAF V600E (papillary) vs β-catenin/CTNNB1 (adamantinomatous) craniopharyngioma molecular split — newer, increasingly asked.

Rapid revision

1. Anterior pituitary = Rathke's pouch (oral ectoderm); posterior = neuroectoderm.
2. Basophils → B-FLAT (FSH, LH, ACTH, TSH); acidophils → GH, PRL.
3. Prolactinoma = most common functioning adenoma; cabergoline is DOC.
4. Microadenoma < 1 cm, macroadenoma ≥ 1 cm; macro → bitemporal hemianopia.
5. Acromegaly: screen with IGF-1, confirm with OGTT (no GH suppression), treat surgically / octreotide.
6. GH excess before epiphyseal fusion → gigantism; after → acromegaly; cardiomyopathy is the chief killer.
7. Craniopharyngioma: Rathke pouch; child = adamantinomatous, machine-oil fluid + cholesterol crystals + calcification + wet keratin; adult = papillary (BRAF V600E).
8. Sheehan syndrome: postpartum haemorrhage → anterior pituitary infarction → failure of lactation + amenorrhoea; posterior pituitary spared.
9. Central DI responds to desmopressin; nephrogenic DI (lithium, hypercalcaemia) does not.
10. Pituitary apoplexy = acute haemorrhage into adenoma → sudden headache + visual loss → emergency.
11. Crooke's hyaline change = sign of cortisol excess; reticulin loss distinguishes adenoma from hyperplasia.
12. Empty sella = CSF in sella; stalk effect = mild hyperprolactinaemia from any sellar mass.