Pituitary Adenoma

Pituitary adenomas are benign neoplasms arising from the anterior pituitary (adenohypophysis), representing 10-15% of intracranial tumors. They are classified by: size (microadenoma <10 mm, macroadenoma ≥10 mm, giant adenoma ≥40 mm), hormonal activity (functioning 65% — secretes excess hormone, vs nonfunctioning 35% — clinically silent), cell of origin (lactotroph/prolactinoma 40-50%, somatotroph/GH-secreting 10-15% causing acromegaly, corticotroph/ACTH-secreting 4-8% causing Cushing's disease, gonadotroph 15-20% mostly silent, thyrotroph/TSH-secreting 1-2% causing thyrotoxicosis, mixed/null cell 10-15%), and invasiveness (Knosp grade 0-4 for cavernous sinus invasion).

Pathophysiology involves monoclonal proliferation of pituitary cells with various molecular drivers: GNAS mutations (40% of somatotroph adenomas), USP8 mutations (Cushing's disease), familial syndromes (MEN1, MEN4, Carney complex, McCune-Albright, AIP-related familial isolated pituitary adenoma). Functioning adenomas cause hormone-specific syndromes: prolactinoma (galactorrhea, amenorrhea, infertility, hypogonadism, low libido, gynecomastia in men), acromegaly (acral enlargement, coarse facial features, glucose intolerance, sleep apnea, cardiomyopathy, colon polyps), Cushing's disease (central obesity, moon facies, buffalo hump, striae, hypertension, diabetes, osteoporosis, depression), TSH-oma (hyperthyroidism with inappropriately normal TSH), gonadotropinoma (mostly clinically silent). Mass effect symptoms include headache, visual field defects (bitemporal hemianopia from optic chiasm compression), cranial neuropathies (III, IV, V1, V2, VI from cavernous sinus extension), hypopituitarism, hydrocephalus, CSF rhinorrhea, pituitary apoplexy.

Diagnosis uses pituitary MRI with thin-section dynamic gadolinium contrast as gold standard (microadenomas appear hypoenhancing relative to gland), hormone testing tailored to suspected syndrome (prolactin, IGF-1 + OGTT for GH, late-night salivary cortisol/dexamethasone suppression/24-hour UFC for Cushing's, TSH/free T4/alpha-subunit for TSH-oma, FSH/LH/estradiol/testosterone for gonadotroph), pituitary stimulation/suppression tests (insulin tolerance test, CRH stimulation, IPSS for Cushing's), formal visual field testing (Humphrey perimetry), assessment for hypopituitarism. Treatment depends on tumor type: prolactinoma — first-line dopamine agonists (cabergoline preferred over bromocriptine, normalization in 80-90%); acromegaly, Cushing's, TSH-oma — surgery first-line (transsphenoidal endoscopic resection); nonfunctioning macroadenoma — surgery if vision threatened or growing; medical therapy (somatostatin analogs octreotide/lanreotide/pasireotide, GH receptor antagonist pegvisomant, ketoconazole/metyrapone/osilodrostat for Cushing's), radiotherapy (stereotactic radiosurgery, conventional fractionated) for residual or recurrent disease, hormone replacement for hypopituitarism, lifelong endocrine surveillance.