Male pseudohermaphroditism due to nonsalt-losing 3β-hydroxysteroid dehydrogenase deficiency: Gender role change and absence of gynecomastia at puberty

Adrenal and gonadal functions were evaluated on two adult cousins with male pseudo-hermaphroditism due to congenital 3β-hydroxysteroid dehydrogenase deficiency (3β-HSD) without clinical salt-losing. Both patients had been reared as females since birth. Case 1 presented at age 17 with perineal hypospadias virilization without gynecomastia and a female to male gender role change at puberty. Case 2 had previously undergone bilateral orchidectomy in childhood and presented “primary amenorrhea”, absence of virilization and a female gender role at the age of 24. In the basal state, as well as after ACTH and hCG stimulation, 3β-hydroxy-5-ene-steroid levels were disproportionately elevated, resulting in abnormal 3β-hydroxy-5-ene: 3-oxi-4-ene steroids ratios. Normal basal serum cortisol with inadequate cortisol response to ACTH was observed in both patients. Elevated basal plasma renin activity (PRA) and normal basal serum aldosterone (ALDO) were present in both subjects. After ACTH stimulation serum ALDO rose adequately in Case 1 but subnormally in Case 2. Salt restriction resulted in an increase in serum ALDO and no salt loss in Case 1 whereas in Case 2 the substantial rise in PRA and serum ALDO were unable to prevent slight urinary sodium loss. Case 1 had normal basal serum testosterone with subnormal response to hCG stimulation. Incubation of testicular tissue in vitro with [ 3H]HEA resulted in large Androstenediol production but diminished testosterone conversion confirming the 3β-HSD deficiency in the testes. We conclude that (1) absence of gynecomastia and a female to male gender role change may be observed in the male pubertal presentation of nonsalt-losing 3β-HSD deficiency and (2) the different functional behavior of zona glomerulosa in our patients suggests the presence of variable degrees of 3β-HSD deficiency in the zona glomerulosa of the nonsalt-losing form.