17-Hydroxyprogesterone responses to adrenocorticotropin in children with premature adrenarche

The adrenal secretory response to an iv bolus dose of ACTH was measured in 10 girls (4-8 yr of age), 5 boys (4-9 yr) with premature adrenarche (PA), and 20 normal children. The evening before the ACTH test, each subject took dexamethasone (1 mg at bedtime) to suppress the early morning surge of ACTH. The next morning, 2 serum samples were obtained before the administration of ACTH (Cortrosyn; 0.25 mg), and 2 samples were collected 30 and 45 min after ACTH administration. All samples were assayed for cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, 17-hydroxyprogesterone (17-OHP), and androstenedione. There was no significant difference in the dexamethasone-suppressed steroid levels between the children with PA and the normal children. After ACTH injection, cortisol, DHEA, 17-OHP, and androstenedione increased significantly. There was no significant change in DHEA sulfate. The mean 17-OHP response to ACTH in girls with PA was significantly higher than that in girls and women whose pubertal development was normal. This response was similar in magnitude to that in a group (n = 5) of obligate heterozygotes for congenital adrenal hyperplasia (CAH). These data suggest that many girls with PA have a mild adrenal steroid secretory defect that resembles the response in adult obligate heterozygotes for CAH due to 21-hydroxylase deficiency. In contrast to the girls, none of the boys with PA had an exaggerated 17-OHP response to ACTH. Thus, these boys had no evidence for an adrenal steroid secretory defect. In summary, although the clinical presentation of boys with PA is similar to that of girls with PA, there is a significant difference in the adrenal steroid secretory response to ACTH. Thus, the biochemical events that cause PA in boys may be different from the corresponding events in girls.