Hypo- and hyperfunctions of the hypothalamic-hypophysial system

1. Hypothalamo-Hypophyseal System

Anatomy

• Hypothalamus: links nervous ↔ endocrine systems via pituitary (hypothalamo-hypophyseal system).
• Hypophysis (pituitary): pea-sized; connected to hypothalamus by infundibular stalk.
• Adenohypophysis (anterior pituitary): regulated by hypothalamic releasing/inhibiting factors.
• Neurohypophysis (posterior pituitary): stores ADH + oxytocin from hypothalamic neurons.

Hypothalamic releasing factors → Pituitary hormones

Hypothalamic factor	Pituitary hormone
CRH	→ ACTH
GHRH	→ GH
GnRH	→ FSH + LH
TRH	→ TSH
Dopamine (inhibitory)	→ PRL (inhibits)

2. Hypopituitarism (Hypofunction)

Definition

• Occurs when ≥ 85 % of anterior pituitary parenchyma is lost.

Causes

• Non-functioning pituitary adenomas compressing the gland.
• Ischemic injury:
  • Sheehan syndrome = postpartum hypopituitarism due to pituitary necrosis after severe hypotension / hemorrhage during/after delivery.
• Metastatic tumors: breast, lung.
• Inflammatory reactions, trauma, surgery, radiation.
• Empty sella syndrome.

Clinical course (depends on deficient hormone)

• GH deficiency → children: pituitary dwarfism (growth failure).
• GnRH deficiency → amenorrhea + infertility (women), impotence (men).
• TSH deficiency → hypothyroidism.
• ACTH deficiency → hypoadrenalism.
• Prolactin deficiency → failure of postpartum lactation (classic Sheehan presentation).

3. Hyperpituitarism (Hyperfunction)

Causes

• #1 cause = adenoma of anterior lobe.
• Hyperplasia: pregnant women (gland nearly doubles — lactotrophs + somatotrophs).
  • Sheehan syndrome: enlarged pregnancy pituitary becomes hypoxic if massive hemorrhage → infarct → loss of hormone-producing cells.

4. Pituitary Adenomas

Classification

• Size:
  • Microadenoma < 1 cm
  • Macroadenoma > 1 cm
• Sporadic or familial (part of MEN-1).
• Hormonal activity:
  • Hormonally active — hormone excess + clinical Sx.
  • Silent — hormone production but no Sx.
  • Hormone-negative — no immunohistochemical reactivity.

Morphology

• Usually well-circumscribed, soft.
• Small → confined to sella turcica.
• Large → compress optic chiasm → bitemporal hemianopsia; erode sella; extend into cavernous/sphenoidal sinuses.
• Cellular monomorphism + absence of reticulin meshwork distinguish adenoma from normal parenchyma.

5. Specific Adenoma Types

A) Prolactinoma (~30 % — most common functional)

• Most common hyperfunctioning adenoma.
• Hyperprolactinemia → amenorrhea + galactorrhea + loss of libido + infertility in women.
• More obvious in premenopausal women → detected early.
• In men/postmenopausal women: usually large at diagnosis (mass effect).
• Tx: dopamine agonists (bromocriptine, cabergoline).

B) GH-producing adenoma (gigantism / acromegaly) — 2nd most common

• GH → hepatic IGF-1 secretion → mediates effects.
• Gigantism: childhood, before epiphyseal closure → generalized ↑ body size with disproportionately long arms/legs.
• Acromegaly: adulthood, after epiphyseal closure →:
  • Growth of soft tissue, skin, viscera.
  • Enlargement of bones in face, hands, feet.
  • Jaw protrusion (prognathism), broadening of lower face, separation of teeth.
  • Sausage-like fingers.
• Associations: DM, osteoporosis, HTN, cardiomyopathy, colon polyps.

C) ACTH-producing adenoma (Cushing disease)

• Most small (microadenomas) at diagnosis.
• ↑ ACTH → adrenal cortex stimulation → hypercortisolism (Cushing disease).
• Nelson syndrome: after bilateral adrenalectomy for Cushing disease → loss of cortisol feedback → large aggressive corticotroph adenoma + hyperpigmentation (↑ MSH from POMC cleavage).

D) TSH / FSH / LH adenomas (gonadotroph / thyrotroph)

• Rare, often difficult to recognize (inefficient secretion).
• Gonadotroph adenomas: middle-aged adults; usually present with mass effect / neurologic symptoms (large tumors).

6. Pituitary Carcinoma

• Extremely rare.
• Most malignant brain tumors stay intracranial — pituitary carcinoma is the only exception → extracranial metastases.
• More common: metastases TO pituitary from breast + lung cancer.

7. Posterior Pituitary Syndromes

Hormones

• ADH → water resorption in collecting ducts.
• Oxytocin → uterine contraction + milk ejection.

A) SIADH (Syndrome of Inappropriate ADH)

• Excess ADH → excessive water resorption.
• Causes: small cell lung cancer (paraneoplastic), CNS lesions, drugs, pulmonary disease.
• Sx: hyponatremia, cerebral edema, neurologic dysfunction (confusion, seizures).

B) Diabetes Insipidus

• Central: ADH deficiency (brain trauma, neoplasm).
• Nephrogenic: renal tubular unresponsiveness to ADH (lithium, hypercalcemia).
• Sx: large volume of dilute urine, hypernatremia, thirst, polydipsia.

8. Comparison — SIADH vs DI

Feature	SIADH	Diabetes Insipidus
ADH	↑↑	↓ (central) or resistant (nephrogenic)
Urine	Concentrated	Dilute, large volume
Serum Na⁺	Hyponatremia	Hypernatremia
Symptoms	Cerebral edema, seizures	Polyuria, polydipsia

💡 High-yield: Hypopituitarism = ≥ 85 % loss; classic = Sheehan syndrome (postpartum, failed lactation). Hyperpituitarism #1 cause = adenoma. Prolactinoma = #1 functional, amenorrhea + galactorrhea, dopamine agonists (bromocriptine). GH adenoma = gigantism (pre-epiphyseal) / acromegaly (post-epiphyseal, prognathism + sausage fingers + DM). ACTH adenoma = Cushing disease (microadenoma); Nelson syndrome post-adrenalectomy. Mass effect → bitemporal hemianopsia (optic chiasm compression). MEN-1 = familial. SIADH = ↑ ADH → hyponatremia + cerebral edema. Diabetes insipidus = central (↓ ADH) / nephrogenic (resistance); polyuria + hypernatremia.