Deficient inactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase in essential hypertension

Abstract

Objective: 11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. 11 beta-Dehydrogenase deficiency, either congenital or after inhibition by liquorice and carbenoxolone, results in cortisol-dependent mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hypertension.

Design/patients: Twenty patients with essential hypertension were compared with 19 matched healthy controls.

Measurements: 11 beta-Hydroxysteroid dehydrogenase activity was assessed by the half-life of 11 alpha-3H-cortisol, and by the ratios of cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor activation was assessed by plasma potassium, renin activity and aldosterone.

Results: Half-lives of 11 alpha-3H-cortisol were prolonged in a subgroup of hypertensives (mean +/- SE 53.2 +/- 3.6 min in hypertensives vs 42.3 +/- 2.3 in controls, P < 0.05; seven of the 20 hypertensives had half-lives exceeding 2 SD of controls). Ratios of cortisol to cortisone in plasma and of their metabolites in urine were not different. 11 alpha-3H-Cortisol half-lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation.

Conclusions: 11 beta-Dehydrogenase is defective in a proportion of patients with essential hypertension. The normal ratios of cortisol to cortisone in plasma and of their metabolites in urine, also seen after carbenoxolone administration, suggest that 11 beta-reductase conversion of cortisone to cortisol is also defective. Unlike other syndromes of 11 beta-dehydrogenase deficiency, the defect was not associated with mineralocorticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to cortisol.