A 45-year-old woman has galactorrhea, amenorrhea, and MRI showing a 1.2 cm sellar mass. Serum prolactin is 280 ng/mL. The pathological basis of macroprolactinoma growth is primarily driven by:
- A Loss of dopaminergic inhibition allowing estrogen-driven lactotroph proliferation via ERalpha ✓
- B Gain-of-function GNAS mutation causing constitutive Gs-alpha activation
- C MEN1 (menin) loss-of-function mutation in sporadic cases
- D RET mutation activating PI3K/AKT proliferation pathway
Explanation
Dopamine (from the hypothalamus via the portal circulation) is the primary physiological inhibitor of lactotroph proliferation and prolactin secretion, acting via D2 receptors. Lactotrophs also express estrogen receptor alpha (ERalpha); estrogen is trophic and stimulates PRL gene transcription. Prolactinomas arise from lactotrophs and are treated with dopamine agonists (cabergoline, bromocriptine) that restore the inhibitory signal. GNAS gain-of-function mutations (causing Gs-alpha activation) are the key event in somatotroph adenomas (acromegaly, ~40%). MEN1 mutations cause familial prolactinomas (rare). RET mutations cause MEN2.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.