SYNDROME OF APPARENT MINERALOCORTICOID EXCESS ASSOCIATED WITH DEFECTS IN THE PERIPHERAL METABOLISM OF CORTISOL

A syndrome is described whose features, suggestive of primary mineralocorticoid excess, included hypertension, hypokalemia, low PRA, and responsiveness to spironolactone. Aldosterone levels were subnormal but as yet there has been no evidence of overproduction of other mineralocorticoids by chemical analysis or by bioassay of plasma and urinary extracts. The steroidal abnormalities that were observed involved peripheral metabolism rather than secretion. One patient exhibited a transient delay in reduction of the 3-keto group in the A ring, and both patients exhibited a decrease in the metabolism of cortisol to biologically inactive cortisone. This was shown by the marked decrease in the excretion of urinary metabolites bearing an 11-keto group and a decrease in the oxidation of 11α-[3H]cortisol to tritiated water. The defect appeared not to be a deficiency of the 11β-oxidoreductase system itself, since the reverse reaction of conversion of cortisone to cortisol proceeded normally, but, rather, an alteration in the equilibrium position of 11β-oxidoreduction in favor of the reduced form. This was also expressed by a prolongation of the half-time of disappearance of cortisol. The decrease in the MCR permitted the maintenance of normal cortisol plasma levels and normal glucocorticoid function at a diminished rate of secretion. The decreased rate of conversion of cortisol to cortisone serves as a biochemical marker of this hypertensive syndrome. © 1979 by The Endocrine Society.