A patient on long-term dexamethasone (a pure glucocorticoid) develops severe hypokalemia and edema but no hyperglycemia. The hypokalemia is due to which property of dexamethasone?

• A Dexamethasone has significant mineralocorticoid activity at high doses
• B Dexamethasone inhibits 11-beta-hydroxysteroid dehydrogenase, allowing cortisol to activate mineralocorticoid receptors ✓
• C Dexamethasone has no mineralocorticoid activity; hypokalemia suggests concurrent primary hyperaldosteronism
• D Dexamethasone crosses the blood-brain barrier causing SIADH

Explanation

Dexamethasone itself has no mineralocorticoid activity. However, it can inhibit 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), the enzyme that normally inactivates cortisol in the kidney. This allows cortisol to activate mineralocorticoid receptors, producing pseudohyperaldosteronism with hypokalemia and edema. This is the mechanism of licorice-induced hypertension as well.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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