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

Clin Endocrinol (Oxf). 1993 Aug;39(2):221-7. doi: 10.1111/j.1365-2265.1993.tb01778.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Adult
  • Aldosterone / blood
  • Carbenoxolone / pharmacology
  • Cortisone / metabolism
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Hypertension / blood
  • Hypertension / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Potassium / blood
  • Renin / metabolism


  • Aldosterone
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Renin
  • Carbenoxolone
  • Potassium
  • Cortisone
  • Hydrocortisone