Decreased Urinary C19and C21Steroid 5α-Metabolites in Parents of Male Pseudohermaphrodites with 5α- Reductase Deficiency: Detection of Carriers*

Abstract

The urinary 5β/5α ring A-reduced metabolites of C₁₉ and C₁₂ steroids from obligate carrier parents of male) pseudohermaphrodites with 5a-reductase deficiency were analyzed by gas chromatography. Etiocholanolone/androsterone, 11β-hydroxyetiocholanolone/ 11β- hydroxyandrosterone, tetra-hydrocortisol/allotetrahydrocortisol, and tetrahydrocorticoster-one/allotetrahydrocorticosterone were the paired 5β/5α-metab-olite ratios measured. Increased mean 5β/5α 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/allotetrahydro-corticosterone ratio, while in women, the etiocholanolone/an- drosterone ratio was more diagnostic. In obligate carrier men, plasma testosterone, dihydrotestosterone, androstenedione, and 17α-hydroxyprogesterone levels were normal, as were testosterone/dihydrotestosterone ratios. These studies demonstrate a generalized defect in 5α-reductase activity involving C₁₉ and C₁₂ 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 5α-reductase deficiency suggest that there is a carrier rate within the general population, although the exact frequency remains unknown.