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Cortisol Spillover

Meaning

Cortisol Spillover is a molecular endocrinology phenomenon where high local concentrations of the glucocorticoid cortisol exceed the inactivating capacity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in mineralocorticoid target tissues, such as the kidney. Under normal circumstances, 11β-HSD2 rapidly converts cortisol into its inactive metabolite, cortisone, protecting the mineralocorticoid receptor (MR) from cortisol binding. When this enzymatic barrier is overwhelmed, the excess cortisol “spills over” and binds to the MR, acting as a potent mineralocorticoid, which can lead to hypertension and hypokalemia, clinically mimicking primary aldosteronism.