Genetic Defects of Steroidogenesis in Premature Pubarche*

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Abstract
Twenty three patients (19 girls, 4 boys) presented with typical features of premature pubarche between the ages of 2–7 yr. The patients were studied for the presence of an adrenal steroidogenic defect by ACTH stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Based on published nomogram standards for serum 17-hydroxyprogesterone (17-OHP), seven patients (30%) were diagnosed as having the nonclassical symptomatic form of 21-hydroxylase deficiency [mean post ACTH 4244 ± 1113 (sd) ng/dl]. Three patients (13%) were diagnosed to have a mild form of 3β-hydroxysteroid dehydrogenase deficiency based upon the response of serum Δ5-17-hydroxypregnenolone (Δ5-17P) and dehydroepiandrosterone, and the ratio of Δ5-17P/17-OHP to ACTH stimulation (Δ5-17P: 1543 ± 272 ng/dl vs. Tanner stage I control subjects, 350 ± 197 ng/dl; dehydroepiandrosterone: 675 ± 190 ng/dl vs. Tanner stage I control subjects, 82 ± 79 ng/dl; Δ5-17P/17-OHP: 8.1 ± 2.6 vs. Tanner stage I control subjects, 1.4 ± 0.6). No enzyme defect could be identified in the remaining 13 patients (57%). Eleven patients with premature pubarche, with and without an adrenal enzymatic defect, underwent dexamethasone suppression. In all patients the measured steroid levels were suppressed. Thus, the dexamethasone suppression test alone did not distinguish the pathogenesis of premature pubarche. In conclusion, premature pubarche is more commonly due to a partial enzyme defect in adrenal steroidogenesis than has been previously recognized.