148 17-KETOREDUCTASE AND PARIAL ADRENAL 3β-HYDROXYSTEROID-DEHYDROGENASE (3β-HSD) DEFICIENCY

Abstract

A patient with female phenotype at birth, a history of bilateral inguinal hernia and karyotype 46, XY was considered to have MPH due to testicular feminization syndrome until 13 years of age when she developed clitoromegaly (3.5 × 1.8 cm), a deep-pitched voice and breast development. The blind vaginal pouch ended at 3cm and no prostatic tissue was palpable at rectal examination. Peripheral serum steroid analyses revealed markedly elevated levels of androstenedione (Δ4)(4.20 ng/ml) and DHEA (9.50 ng/ml) and moderately raised concentrations of testosterone (T)(1.72 ng/ml). The finding of an elevated Δ4/T ratio was consistent with 17-ketoreductase deficiency. Spermatic vein blood with an even higher Δ4/T ratio (22:1 suggested testicular origin of the increased secretion of Δ4. Neither HCG nor ACTH administration caused further significant increases of Δ4 or T, whereas DHEA showed a 3-fold rise after ACTH. The gaschromatographic profile of urinary steroid metabolites indicated predominance of So-reduced steroids. Surgical exploration foi gonadectomy revealed an inguinal right and an abdominal left testicle. No remnants of the Mullerian ducts could be found. Histologically, both gonads showed epididymes and vasa deferentia as well as atrophic testicular tissue with Leydigcell hyperplasia, Sertoli cells and few spermatogonia. Genital skin fibroblasts exhibited normal androgen binding and 5o-reductase activity. After gonadectomy Δ4 and T levels fell to normal; DHEA,however, remained strikinqly hiqh (17 ng/ml) suggesting a coexisting partial adrenal 3β-HSD deficiency.