A 38-year-old woman presents with hypertension, hypokalemia, and a 2.5 cm right adrenal adenoma on CT with lipid-rich appearance (HU < 10 on unenhanced CT). Biochemistry confirms primary aldosteronism. Adrenal vein sampling (AVS) shows a lateralization ratio of 4:1. Pathologically, which somatic mutation is most commonly found in aldosterone-producing adenomas (APAs)?

• A KCNJ5 gene mutation causing altered K+/Na+ channel selectivity and inappropriate aldosterone secretion ✓
• B RET proto-oncogene mutation as in MEN2A
• C VHL mutation causing constitutive HIF-1 activation and catecholamine production
• D PRKAR1A mutation causing Carney complex with cortisol excess

Explanation

KCNJ5 mutations (encoding the inward-rectifier potassium channel Kir3.4) are found in approximately 40–60% of aldosterone-producing adenomas, making it the most common somatic mutation. These mutations (typically G151R or L168R) alter channel selectivity, allowing Na+ to enter the zona glomerulosa cell instead of K+, causing membrane depolarization, calcium channel opening, and constitutive CYP11B2 (aldosterone synthase) activation independent of angiotensin II. Other APA mutations include ATP1A1, ATP2B3, CACNA1D, and CTNNB1. AVS lateralization >4:1 guides unilateral adrenalectomy. VHL is for pheochromocytoma/renal cell carcinoma; PRKAR1A is for Cushing's in Carney complex.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.