Deficient inactivation of cortisol by 11β‐hydroxysteroid dehydrogenase in essential hypertension

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Abstract
Summary: OBJECTIVE 11β‐Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from Cortisol by converting Cortisol to inactive cortisone. 11β‐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 11β‐Hydroxysteroid dehydrogenase activity was assessed by the half‐life of 11α‐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 11α‐3H‐cortisol were prolonged in a subgroup of hypertensives (mean ± SE 53.2 ± 3.6 min in hypertensivesvs42.3 ± 2.3 in controls,P3H‐Cortisol half‐lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation.CONCLUSIONS 11β‐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 11β‐reductase conversion of cortisone to Cortisol is also defective. Unlike other syndromes of 11β‐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.