Prepubertal Diagnosis of Steroid 5α-Reductase Deficiency*

Abstract

The diagnosis of 5 alpha-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, urogenital sinus, 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 5 beta-T metabolites in urine (8.1 and 6.0 vs. normal, less than 1),3) deficient conversion of T to DHT during [3H] T infusion (0.3 and 0.4% vs. normal, 5.3 +/- 3), 4) deficient conversion of [14 C] T to 5 alpha-reduced metabolites by nongenital skin fibroblasts (2.2 and 1.9 pmol/microgram DNA/nmol substrate vs. 68.4+/- 7.8 Pmol/microgram 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 in in T binding is demonstrated by the observation that binding of [3H]DHT to cytosol of skin fibroblasts was normal (4.2 dpm/micrograms DNA vs. normal male values of 3.7 +/- 0.64). Thus, the present report suggests that 5 alpha-reductase deficiency can be diagnosed during childhood and even after castration by metabolic studies of nongenital skin fibroblasts and determination of the conversion ratio of [3H]T to [3H]DHT in plasma.

Steroid 5α-Reductase Deficiency and Posterior Urethral Valves

“…Following three daily doses of 1,500 units of human chorionic gonadotro phin, plasma testosterone rose to 21 nmol/1 and dihydroteslosterone to 0.35 nmol/1, a ratio of 60:1. These results are compatible with steroid 5a-reductase defi ciency [7,8]. Plasma testosterone and dihydrotestostcrone were measured by radioimmunoassay by meth ods described in the WHO manual [9], There were no abnormal urinary symptoms.…”

5α-Metabolism in Finasteride-Treated Subjects and Male Pseudohermaphrodites with Inherited 5α-Reductase Deficiency

“…Diminished 5a-reductase activity has been demon strated in both tissue slices and fibroblasts cultured from genital skin of MPHs with 5a-reductase deficiency [7][8][9][10][11]. Familial differences demonstrating genetic heterogeneity have been found in tissue studies of enzyme kinetics.…”

Hypospadias in a Male Patient with 21-hydroxylase Deficiency

“…HCG loading test confirmed intact testosterone biosynthesis in the testes that was compatible with the hyperandrogenemia in the neonatal period. T/DHT ratio after hCG loading is reported to be useful in the evaluation of 5-α-reductase-2 activity [10,11]. In our patient, T/DHT ratio after hCG was 7.6, that was considered to be normal.…”