Licorice ingestion can inhibit 11β-hydroxysteroid dehydrogenase type 2, producing hypertension due to which condition?

• A. Addison disease
• B. Cushing syndrome
• C. Apparent mineralocorticoid excess
• D. Liddle syndrome

Answer: (C)

Licorice inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2, which in the kidney normally converts active cortisol to inactive cortisone to prevent cortisol from overstimulating the mineralocorticoid receptor (MR). When this enzyme is blocked, cortisol can activate MR, causing sodium reabsorption and potassium loss in the distal nephron. The result is increased blood volume and hypertension with hypokalemia, even though aldosterone levels are not elevated—the situation is termed apparent mineralocorticoid excess. Addison disease would cause hypotension from adrenal failure; Cushing syndrome involves cortisol excess but not via MR activation; Liddle syndrome is due to a gain-of-function in ENaC channels, not 11β-HSD2 inhibition.