A 35-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. CT abdomen shows a 1.8 cm right adrenal adenoma. Adrenal vein sampling confirms right-sided aldosterone excess. The pathological basis of autonomous aldosterone secretion in this adenoma involves mutation in which ion channel/ATPase?

• A SCN5A — voltage-gated sodium channel
• B CYP11B1 — 11β-hydroxylase
• C KCNJ5 (Kir3.4) — inwardly rectifying potassium channel ✓
• D NR3C2 — mineralocorticoid receptor

Explanation

Aldosterone-producing adenomas (APAs) — the cause of primary hyperaldosteronism (Conn syndrome) — most commonly harbor somatic KCNJ5 mutations (~40% of APAs in Western populations, >60% in Asian populations). KCNJ5 encodes Kir3.4, a potassium channel. Loss-of-function mutations increase sodium conductance through the channel, causing chronic membrane depolarization of adrenocortical cells → activation of voltage-gated calcium channels → elevated intracellular Ca²⁺ → continuous CYP11B2 (aldosterone synthase) stimulation → autonomous aldosterone production independent of angiotensin II. Other mutated genes in APAs include ATP1A1, ATP2B3, CACNA1D, and CTNNB1.

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

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Written and medically reviewed by the StethoPrep medical team.