Normal Gestation and Diminished Androgen Responsiveness in an Untreated Patient with 21-Hydroxylase Deficiency

Abstract

A 22-year-old woman with 21-hydroxylase deficiency but minimal clinical evidence of androgenization was studied. She had conceived twice and had borne a normal male infant without therapy of any kind. The diagnosis of 21-hydroxylase deficiency was substantiated by the findings of 17- ketosteroid and pregnanetriol excretions of 18.1 and 8.1 mg/24 hours, respectively. Adequate basal compensation was indicated by a fasting plasma cortisol of 17.5 μg/dl. Plasma ACTH (207 pg/ml), testosterone (216 ng/dl) Δ⁴-androstenedione (649 ng/dl), progesterone (249 ng/dl) and 17α-hydroxyprogesterone (4820 ng/dl) were all significantly elevated. Circulating levels of these steroids increased after exogenous ACTH, decreased after dexamethasone, and were unaffected by oral estrogen, indicating their adrenal origin. Plasma dihydrotestosterone 125 ng/dl) was elevated in proportion to the testosterone, indicating adequacy of 5α-hydroxysteroid reductase activity. Fibroblasts, cultured from a biopsy of wrist skin, had a binding capacity of 89 × 10⁻¹⁸ moles/μg DNA for ³H-dihydrotestosterone, which was in the lower portion of the normal range of 60-675 × 10⁻¹⁸ moles/μg. We interpret these data to suggest that the absence of significant virilization in this patient could be due to partial androgen resistance.