Late-Onset Adrenal Steroid 3β-Hydroxysteroid Dehydrogenase Deficiency. I. A Cause of Hirsutism in Pubertal and Postpubertal Women*

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Abstract
To investigate the adrenal cause of hyperandrogenism in peri- and postpubertal hirsute women, baseline and ACTH-stimulated serum concentrations of Δ5-l7-hydroxypregnenolone(Δ6-17P), dehydroepiandrosterone (DHEA) and its sulfate, 17-hydroxyprogesterone (17-OHP), cortisol, Δ4-androstenedione, and testosterone were determined in 116 women with hirsutism or acne of peri- and postpubertal onset with or without menstrual abnormalities. The results were comparedwith the same steroid concentrations in 30 normal age-matched women. Sixteen of the 116 women with hirsutism whose ACTHstimulated 17-OHP levels (mean ± SD, 5404 ± 3234 ng/ normal, 334 ± 194) were markedly elevated while their ratios of Δ6-17P to 17-OHP (0.4 ± 0.2; normal, 3.4 ± 1.5) were low were diagnosed as having nonclassical symptomatic 21-hydroxylase deficiency. Seventeen other hirsute women, including 3 siblings had very high responses of Δ5-17P (2276 ± 669 ng/dl; normal, 985 ± 327) and DHEA (2787 ± 386 ng/dl; normal, 1050 ± 384) to ACTH stimulation, with significantly elevated ratios of A8-17P to 17-OHP (11 ± 2.0; normal, 3.4 ± 1.5) and DHEA to Δ4-androstenedione (7.5 ± 2.3; normal, 4.6 ± 1.5). In these hirsute women, the morning serum Δ6-17P and DHEA concentrations were elevated, had a diurnal variation, and were suppressed with dexamethasone administration. We propose that partial adrenal 3β-hydroxysteroid dehydrogenase deficiency is the cause of hirsutism in these women. This may represent an allelic variant at the genetic locus for 3β-hydroxysteroid dehydrogenase deficiency similar to that reported for symptomatic nonclassical 21-hydroxylase deficiency producing peripubertal excess androgen syndrome..