Apparent cortisone reductase deficiency: A functional defect in 11 beta-hydroxysteroid dehydrogenase type 1

A 36-yr-old woman was referred to the endocrine clinic for investigation of oligomenorrhea, hirsutism, and acne. She was plethoric and overweight with central fat distribution. Plasma cortisol was normal, but her adrenal glan ds were enlarged (CT scan). Urinary tetrahydrocortisone excretion rate was consistently high, raising the possibility of 11 beta-hydroxysteroid dehydr ogenase type 1 (11 beta-HSD1) deficiency. In addition, 5 beta- reduction of cortisol and cortisone was markedly enhanced. The levels of all cortisol m etabolites were suppressed normally with dexamethasone, but conversion of o ral cortisone acetate to plasma cortisol was delayed and subnormal compared with that of healthy volunteers. This was accompanied by a larger than nor mal increase in plasma cortisone concentration. Thus, the defect appears to be in 11 beta-HSD1 activity and not in 5 beta-reductase activity. Three cl ose relatives of the subject showed no comparable abnormalities, and analys is of the coding region and exon/intron boundaries of the 11 beta-HSD1 gene of the case revealed no differences from the consensus sequence. The defec t may lie outside the coding region. Alternatively, some other inherited or acquired defect may lead to inhibition of this enzyme system.