Decreased urinary C19 and C21 steroid 5 alpha-metabolites in parents of male pseudohermaphrodites with 5 alpha-reductase deficiency: detection of carriers.

The urinary 5 beta/5 alpha ring A-reduced metabolites of C19 and C21 steroids from obligate carrier parents of male pseudohermaphrodites with 5 alpha-reductase deficiency were analyzed by gas chromatography. Etiocholanolone/androsterone, 11 beta-hydroxyetiocholanolone/11 beta-hydroxyandrosterone, tetrahydrocortisol/allotetrahydrocortisol, and tetrahydrocorticosterone/allotetrahydrocorticosterone were the paired 5 beta/5 alpha-metabolite ratios measured. Increased mean 5 beta/5 alpha ratios were found for all paired metabolites compared to mean ratios in normal subjects. In men, the highest index of discrimination of the carrier state was the tetrahydrocorticosterone/allotetrahydrocorticosterone ratio, while in women, the etiocholanolone/androsterone ratio was more diagnostic. In obligate carrier men, plasma testosterone, dihydrotestosterone, androstenedione, and 17 alpha-hydroxyprogesterone levels were normal, as were testosterone/dihydrotestosterone ratios. These studies demonstrate a generalized defect in 5 alpha-reductase activity involving C19 and C21 steroid metabolism in obligate carrier parents and provide further confirmation of an autosomal recessive mode of inheritance in this condition. The data from parents of sporadic cases of male pseudohermaphrodites with primary 5 alpha-reductase deficiency suggest that there is a carrier rate within the general population, although the exact frequency remains unknown.