A 42-year-old man who regularly consumes large amounts of licorice presents with hypertension, hypokalemia, metabolic alkalosis, and suppressed plasma renin and aldosterone. His mineralocorticoid excess is best explained by inhibition of which enzyme?

• A Aromatase in adipose tissue
• B 21-hydroxylase in the zona glomerulosa
• C 5-alpha reductase in the distal nephron
• D 11-beta-hydroxysteroid dehydrogenase type 2 in renal tubular cells ✓

Explanation

The mineralocorticoid receptor binds cortisol with affinity equal to or greater than aldosterone. Renal specificity depends on 11-beta-HSD type 2, which oxidizes cortisol to inactive cortisone. Glycyrrhetinic acid in licorice inhibits this enzyme, so circulating cortisol floods the receptor, producing apparent mineralocorticoid excess with low renin and aldosterone. 21-hydroxylase deficiency instead lowers aldosterone synthesis and raises precursors.

Reference: Williams Textbook of Endocrinology, 14th ed.

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