11-BETA-HYDROXYSTEROID DEHYDROGENASE DEFICIT - A RARE CAUSE OF ARTERIAL-HYPERTENSION - DIAGNOSIS AND THERAPEUTIC APPROACH IN 2 YOUNG BROTHERS

We report the clinical history and results of endocrine investigations in two brothers born to consanguineous parents, who presented with hy pokalemia and arterial hypertension when they were aged 2 and 6 years. The hormonal serum assay results, including extremely low values for aldosterone and plasma renin activity, favored the existence of appare nt mineralocorticoid excess, A diagnosis of 11 beta-hydroxysteroid deh ydrogenase (11 beta-HSD) deficiency was made, based on assays of the h ydrogenated urinary metabolites of cortisol and cortisone, as well as of corticosterone and dehydrocorticosterone. Indeed we found a very lo w rate of urinary elimination of cortisone metabolites: tetrahydrogena ted cortisone was reduced to between 0.10 and 30 mu mol/24 h, which is 15-100 times lower than the normal rate; hexahydrogenated cortolones alpha and beta were found to be 7- to 20-fold lower than normal levels ; and the 11 -keto-17-ketosteroid derivatives of cortisone were also r educed, Urinary elimination of the cortisol-reduced metabolites 5 beta - and 5 alpha-tetrahydrogenated cortisol were slightly reduced or norm al. These results argue in favor of a deficit in the enzyme 11 beta-HS D, which oxidizes cortisol into cortisone. A moderate defect in the co nversion of cortisol into 5 beta-THF compared to normal conversion int o 5 alpha-THF was also found. With respect to corticosterone metabolis m, we demonstrated the presence of a defect in the oxidation of that s teroid into dehydrocorticosterone, also due to the deficit in 11 beta- HSD, Arterial hypertension and hypokalemia were corrected by treatment with dexamethasone, concomitantly with correction of the low aldoster one and plasma renin activity levels, On the other hand, during this t reatment, urinary concentrations of the metabolites of cortisol, corti sone and corticosterone were only moderately affected.