title: Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.
abstract: Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.
mesh_terms: D000303:Adrenal Cortex Diseases / Q000209:etiology / Q000652:urine*; D000324:Adrenocorticotropic Hormone / Q000652:urine*; D000328:Adult; D001327:Autoimmune Diseases / Q000150:complications; D002849:Chromatography, Gas; D003366:Cosyntropin; D003480:Cushing Syndrome / Q000150:complications; D003907:Dexamethasone; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000652:urine
chemical_list: D013256:Steroids; D003366:Cosyntropin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone