Pituitary disorders
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Pituitary Disorders - Comprehensive Exam Review
Anatomy & Physiology Recap
The pituitary sits in the sella turcica and has two lobes:
| Lobe | Hormones | Blood Supply |
|---|---|---|
| Anterior (adenohypophysis) | GH, PRL, TSH, ACTH, LH, FSH | Hypophyseal portal venous system (low-pressure) |
| Posterior (neurohypophysis) | ADH (vasopressin), Oxytocin | Direct arterial branches |
The anterior pituitary is the "command center" regulating adrenal, thyroid, and gonads. The posterior pituitary is an extension of hypothalamic neurons - oxytocin and vasopressin are produced in the hypothalamus and transported down axons for storage and release.
Key regulatory principle: Hypothalamic releasing hormones stimulate anterior pituitary secretion; dopamine tonically inhibits prolactin.
I. HYPERPITUITARISM (Excess Hormone Secretion)
Pituitary Adenomas - The Core Concept
The most common cause of hyperpituitarism is an anterior lobe pituitary adenoma (neuroendocrine tumor). Key exam facts:
- Microadenoma = <1 cm | Macroadenoma = >1 cm
- Macroadenomas cause mass effects (especially visual disturbances via optic chiasm compression - bitemporal hemianopia)
- Genetic mutation: GNAS gene mutation causing constitutive activation of stimulatory G protein (one of the more common alterations)
- Morphology: cellular monomorphism + absence of reticulin network are the two distinctive features
- Pituitary carcinomas are exceedingly rare; they extend beyond the sella and metastasize
- Robbins & Kumar Basic Pathology
A. Prolactinoma (Lactotroph Adenoma)
Most common functional pituitary adenoma.
Clinical features:
- Women: amenorrhea, infertility, galactorrhea (the classic triad)
- Men: impotence, loss of libido, infertility (often present late with CNS compression symptoms - headaches, visual defects)
- Galactorrhea associated with amenorrhea is a self-limiting disorder with moderately elevated PRL
Diagnosis:
- PRL >200 µg/L almost invariably indicates a prolactin-secreting adenoma
- PRL <100 µg/L - may be microadenoma, other sellar lesion, or non-neoplastic cause
- MRI should be performed in all patients with hyperprolactinemia
Other causes of hyperprolactinemia to exclude (exam favorite):
- Drugs: dopamine receptor blockers (haloperidol, chlorpromazine, risperidone), metoclopramide, verapamil, opiates, TCAs, SSRIs (fluoxetine), estrogens, cimetidine
- Physiologic: pregnancy, breastfeeding
- Hypothyroidism (TRH stimulates PRL)
- Chronic renal failure, cirrhosis
Treatment:
- Dopamine agonists (cabergoline, bromocriptine) are the mainstay
- Cabergoline (0.5-1.0 mg twice weekly) - achieves normoprolactinemia in ~80% of microadenomas, shrinks ~70% of macroadenomas
- Cabergoline is preferred over bromocriptine (longer-acting, higher D2 affinity, better tolerated)
- Microadenomas: may just monitor if asymptomatic and no fertility desire
- After 2 years of normoprolactinemia with microadenoma - can try withdrawing dopamine agonist (monitor carefully for recurrence)
- ~20% of patients (especially males) are resistant to dopaminergic treatment
- Harrison's Principles of Internal Medicine 22E
B. Somatotroph Adenoma (GH-secreting)
Clinical manifestations:
- Gigantism - if excess GH occurs before epiphyseal closure (children)
- Acromegaly - if excess GH occurs after epiphyseal closure (adults): coarsening of facial features, enlarged hands/feet, prognathism, macroglossia, organomegaly
- Impaired glucose tolerance and diabetes mellitus (GH is insulin-antagonistic)
- Associated with galactorrhea in ~1/3 of patients
- Robbins & Kumar Basic Pathology
C. Corticotroph Adenoma (ACTH-secreting) - "Cushing Disease"
Key distinction:
- Cushing Disease = pituitary ACTH-secreting adenoma (the cause)
- Cushing Syndrome = clinical syndrome from any cause of glucocorticoid excess
Clinical features of Cushing syndrome:
- Central obesity, moon face, buffalo hump
- Striae (purple/red), thin skin, easy bruising
- Proximal muscle weakness, osteoporosis
- Hypertension, hyperglycemia
- Hypokalemia (from mineralocorticoid effects of excess cortisol)
- Hyperpigmentation (from excess ACTH stimulating MSH from same POMC precursor)
Adenoma features: Also produces melanocyte-stimulating hormone (MSH) from the same POMC precursor, causing hyperpigmentation.
- Robbins & Kumar Basic Pathology
D. Other Functional Adenomas
| Adenoma Type | Hormone | Clinical Syndrome |
|---|---|---|
| Thyrotroph | TSH | Secondary hyperthyroidism (rare) |
| Gonadotroph | LH/FSH | Usually nonfunctional clinically; mass effects |
| Null cell | None | Mass effects only |
II. HYPOPITUITARISM
Definition: Deficiency of one or more anterior pituitary hormones. Prevalence: 290-455 cases per million; incidence: 42 cases per million per year. Panhypopituitarism = defect in all pituitary hormone lines.
Causes
| Category | Specific Cause |
|---|---|
| Tumors (most common) | Nonfunctioning macroadenoma compressing normal pituitary |
| Ischemic necrosis | Sheehan syndrome (post-partum), DIC, sickle cell anemia, shock |
| Iatrogenic | Surgery, radiation |
| Inflammation | Sarcoidosis, tuberculosis |
| Trauma | Head injury |
| Metastases | Breast, lung |
| Genetic | Transcription factor mutations (Pit-1, PROP1, TPIT, etc.) |
Sheehan Syndrome (key exam topic): Postpartum pituitary necrosis.
- Mechanism: The anterior pituitary enlarges during pregnancy (increase in prolactin-secreting cells) but portal venous blood supply does NOT increase proportionately. This makes it vulnerable to ischemic injury during obstetric hemorrhage/hypotension.
- Posterior pituitary is protected - receives direct arterial supply - so DI from Sheehan is uncommon
- Panhypopituitarism follows as a result
Clinical Manifestations (by hormone lost)
| Hormone Deficient | Clinical Effect |
|---|---|
| GH | Growth failure in children; fatigue, reduced muscle mass in adults |
| FSH/LH (gonadotropins) | Amenorrhea, infertility (women); impotence, loss of libido, loss of pubic/axillary hair (men) |
| TSH | Secondary hypothyroidism |
| ACTH | Secondary hypoadrenalism (life-threatening if missed) |
| PRL | Failure of postpartum lactation |
| MSH (from ACTH precursor) | Skin pallor (loss of melanocyte stimulation) |
Important: In primary adrenal insufficiency - hyperpigmentation. In secondary (ACTH deficiency from pituitary) - skin pallor. This is a classic distinction.
- Robbins & Kumar Basic Pathology; Goldman-Cecil Medicine; Harrison's
III. POSTERIOR PITUITARY DISORDERS
A. Diabetes Insipidus (DI)
Cause: ADH (vasopressin) deficiency or resistance
| Type | Mechanism | Cause |
|---|---|---|
| Central DI | ADH deficiency | Head trauma, neoplasms, inflammatory disorders, surgery, idiopathic |
| Nephrogenic DI | Renal tubular unresponsiveness to ADH | Genetic, lithium, hypercalcemia |
Clinical features:
- Polyuria (large volumes of dilute urine, low specific gravity)
- Polydipsia
- Increased serum Na and osmolality
- Risk of life-threatening dehydration if unable to drink
Key test: Water deprivation test + ADH response (central DI responds to exogenous ADH; nephrogenic does not)
B. SIADH (Syndrome of Inappropriate ADH Secretion)
Cause: ADH overproduction
Common causes:
- Ectopic ADH from malignant neoplasms - particularly small cell carcinoma of the lung (most classic)
- Non-neoplastic pulmonary diseases
- CNS injury/hypothalamic damage
- Drugs (SSRIs, carbamazepine, etc.)
Clinical features:
- Hyponatremia (dilutional) - the dominant feature
- Cerebral edema and neurologic dysfunction
- Normal or slightly increased total body water
- Blood volume stays normal - no peripheral edema (key distinguishing feature)
- Robbins & Kumar Basic Pathology
IV. CRANIOPHARYNGIOMA
A distinct, separate entity - not an adenoma but an important pituitary-region tumor for exams.
- Derived from remnants of Rathke's pouch
- Suprasellar location, often with calcification (visible on CT)
- Bimodal age distribution: children (5-15 yrs) and adults (45-60 yrs)
- Clinical effects: hypopituitarism, visual field defects (chiasm), hydrocephalus
- Adamantinomatous type (children) - contains cholesterol-rich "machine oil" fluid and calcification
- Papillary type (adults) - associated with BRAF V600E mutation
V. EMPTY SELLA SYNDROME
- Sella filled with CSF; pituitary is compressed against its wall
- Primary (defect in diaphragma sellae) or secondary (post-surgery/radiation/infarction)
- Usually asymptomatic but can cause mild hypopituitarism
- Hyperprolactinemia can occur due to stretch on pituitary stalk
Quick Summary Table (High-Yield for Exams)
| Condition | Key Hormone | Classic Presentation | Treatment |
|---|---|---|---|
| Prolactinoma | ↑ PRL | Amenorrhea + galactorrhea (F); impotence (M) | Cabergoline/bromocriptine |
| Acromegaly | ↑ GH | Enlarged acral parts, DM, coarse features | Surgery (transsphenoidal) |
| Cushing disease | ↑ ACTH | Central obesity, striae, hyperglycemia | Surgery |
| Hypopituitarism | ↓ multiple | Depends on deficient hormone; ACTH loss = most dangerous | Hormone replacement |
| Sheehan syndrome | ↓ multiple | Post-partum failure to lactate | Hormone replacement |
| Central DI | ↓ ADH | Polyuria, polydipsia, ↑ Na | Desmopressin (DDAVP) |
| SIADH | ↑ ADH effect | Hyponatremia, ↓ serum osmolality | Fluid restriction; treat cause |
| Craniopharyngioma | Mass effect | Visual field defect + hypopituitarism + calcification on CT | Surgery |
Exam Mnemonics & High-Yield Points
- "Bitemporal hemianopia" = always think pituitary/suprasellar lesion (optic chiasm compression)
- PRL >200 µg/L = prolactinoma until proven otherwise
- Sheehan = postpartum + can't breastfeed + amenorrhea (failure of all anterior pituitary)
- SIADH + small cell lung cancer = classic pair
- Acromegaly in adults, gigantism in children (same adenoma, different epiphyseal status)
- Cushing Disease vs Syndrome: Disease = pituitary; Syndrome = any cause
- Skin pallor in hypopituitarism (↓ MSH) vs hyperpigmentation in Addison's (↑ ACTH/MSH)
- Central DI responds to DDAVP; nephrogenic does not
- Cabergoline preferred over bromocriptine for prolactinoma (longer half-life, better efficacy)
- GNAS mutation in somatotroph adenomas (constitutive Gs activation → ↑ cAMP → ↑ GH)
Sources: Robbins & Kumar Basic Pathology; Goldman-Cecil Medicine; Harrison's Principles of Internal Medicine 22E; Robbins Cotran Pathologic Basis of Disease
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