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.