APPARENT CORTISONE REDUCTASE DEFICIENCY - A UNIQUE FORM OF HYPERCORTISOLISM

We describe two female siblings who had production of cortisol (F; as determined from excretion of urinary metabolites) high enough to give rise to Gushing's disease, but who had no clinical indications of the condition. The teenage patients were hirsute as a result of adrenal hy perandrogenism. A notable feature of the condition was the elevated ex cretion of corticosteroid metabolites with 11-carbonyl groups and very low excretion of 11 beta-hydroxylated steroids. We termed this disord er apparent cortisone (E) reductase disorder. The steroid metabolite p henotype appeared to be the opposite of that seen in the apparent mine ralocorticoid excess syndrome, in which the excretion of 11-keto compo unds is attenuated. As an example, the tetrahydrocortisol plus 5 alpha -tetrahydrocortisol/tetrahydrocortisone ratio was about 0.04 compared to normal values of about 1.0 and apparent mineralocorticoid excess sy ndrome values of 5.0-50.0. Paradoxically, among the F metabolites that had not undergone A-ring reduction, 11 beta-hydroxylated steroids dom inated over Il-carbonyl compounds. The F/E ratio was about 1.8 compare d to an average normal value of 0.54. Neither the father nor the mothe r of the patient had abnormal F metabolite/E metabolite ratios, althou gh the father did excrete highly elevated free E and F, possibly an un related condition. A conclusion was not reached regarding the basis of the disorder. We considered that the most likely causes were 1) defec tive hepatic 11 beta-hydroxysteroid dehydrogenase-1, 2) failure to dev elop the adult form of F metabolism, or 3) excessive activity of A rin g reduction enzymes acting on E.