Prepubertal Diagnosis of Steroid 5α-Reductase Deficiency*

Abstract

The diagnosis of 5α-reductase deficiency was proven in two prepubertal patients with male pseudohermaphroditism (MPH). Both had a 46-XY karyotype and were reared as females; one child had been castrated in infancy. Clitoromegaly, urogenitalsinus, and short vaginal pouch were present in both; inguinal gonads were palpable in one. The diagnosis was made biochemically by observing characteristic changes in five parameters: 1) abnormally high testosterone to dihydrotestosterone (T:DHT) ratio after hCG stimulation (35 and 53 vs. normal, 11 ± 3), 2) abnormally high 5β/5α-T metabolites in urine (8.1 and 6.0 vs. normal, 3H]T infusion (0.3 and 0.4% vs. normal, 5.3 ± 3), 4) deficient conversion of [¹⁴C]T to 5α-reduced metabolitesby nongenital skin fibroblasts (2.2 and 1.9 pmol/μg DNA/nmol substrate vs. 68.4 ± 7.8 pmol/μg DNA/nmol substrate in normal controls), and 5) deficient conversion of [¹⁴C]T to DHT in genital skin slices. The fact that this syndrome represents a defect in T metabolism rather than in T binding is demonstrated by the observation that binding of [³H]DHT to cytosol of skin fibroblasts was normal (4.2 dpm/μg DNA vs. normal male values of 3.7 ± 0.64). Thus, the present report suggests that 5α-reductase deficiency can be diagnosed during childhood and even after castration by metabolic studies of nongenital skin fibroblasts and by determination of the conversion ratio of [³H]T to [³H]DHT in plasma.