Endocrine studies in a pubertal male pseudohermaphrodite with 17-ketosteroid reductase deficiency

A 12 year old child (46,XY) with 17-ketosteroid reductase deficiency was investigated. The patient, reared as a female, was first noted to have clitoromegaly at 10 years of age. Increased facial hair, deepening of the voice, acne, increased body hair and minimal breast development were noted at 12 years. Δ4-Androstenedione (Δ4) in peripheral blood was markedly elevated (1913 ng/100 ml) whereas testosterone (T) was in the male range of Tanner III puberty (240 ng/100 ml). Thus, Δ4/T in this patient was 9.4, compared to a normal ratio of 0.15 to 0.25. T/DHT was normal (10.5). Oestrone (Oe₁) level was slightly elevated (6 ng/100 ml, normal: 2.5-4.5 ng/100 ml). Oestradiol (Oe₂) was normal (1.7 ng/100 ml, normal: 1.5-3 ng/100 ml). Oe₁/Oe₂ was slightly elevated (3.6, normal: 1-2). At laparotomy, testes were found and spermatic vein blood was obtained prior to castration. Androgen determinations of spermatic vein blood demonstrated extremely high Δ4 levels (283 μg/100 ml) and low levels of T (16 μg/100 ml). Δ4/T in spermatic vein was 17, higher than in the peripheral blood, suggesting intact peripheral conversion of Δ4 to T. Incubation of testes slices with Δ4 demonstrated severely impaired conversion to T. Conversion of Oe₁ to Oe₂ was impaired to a lesser degree. 17-ketosteroid reductase deficiency was documented in vivo by impaired conversion of precursor hormones resulting in higher than normal Δ4/T and Oe₁/Oe₂ ratios in blood. In vitro studies with testes slices confirmed the enzymatic defect.