Long-term effects of aminoglutethimide on steroid metabolism in congenital adrenal hyperplasia.
Five cases of congenital adrenal hyperplasia due to C21-hydroxylase defect were treated with a combination of aminoglutethimide and prednisolone. In the third year of treatment the urinary levels of 17-oxosteroids increased above normal values while the total 17-hydroxy-corticosteroids were normally low. Specifically, urinary pregnanetriol was normal in 3 cases. To determine the reasons for this disparity the adrenal metabolism of cholesterol, as judged by the urinary steroid metabolites, was studied. Fractionation of urinary steroid metabolites was by thin-layer chromatography (TLC) followed by gas-liquid chromatography (GLC). The results indicate that aminoglutethimide inhibits steroidogenesis less than prednisolone; that a pathway from cholesterol via 17 alpha, 20 alpha-dihydroxycholesterol to dehydroepiandrosterone is likely to operate after long-term aminoglutethimide therapy; that 11 beta-hydroxylase, at least for pregnenes may be inhibited by aminoglutethimide and that the metabolic breakdown of testosterone may be delayed by this drug.
D015065:17-Hydroxycorticosteroids / Q000652:urine*; D015068:17-Ketosteroids / Q000652:urine*; D000312:Adrenal Hyperplasia, Congenital; D000308:Adrenocortical Hyperfunction / Q000188:drug therapy / Q000652:urine*; D000616:Aminoglutethimide / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D011239:Prednisolone / Q000627:therapeutic use; D011246:Pregnadienetriols / Q000652:urine*; D013250:Steroid Hydroxylases / Q000172:deficiency; D013997:Time Factors
D015065:17-Hydroxycorticosteroids; D015068:17-Ketosteroids; D011246:Pregnadienetriols; D000616:Aminoglutethimide; D002784:Cholesterol; D011239:Prednisolone; D013250:Steroid Hydroxylases