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The Longitudinal Study of Adrenal Maturation during Gonadal Suppression: Evidence That Adrenarche Is a Gradual Process

Divisions of Endocrinology (M.R.P., J.F.C.) and Adolescent Medicine (M.J.M.), Department of Medicine, Children’s Hospital, Boston, Massachusetts 02115; Reproductive Endocrine Unit (M.R.P., W.F.C., P.A.B.) and Pediatric Endocrine Unit (P.A.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Biostatistics Center, General Clinical Research Center, Massachusetts General Hospital (D.L.H.), Boston, Massachusetts 02114; and Esoterix Endocrinology, Inc. (D.W.C.), Calabasas Hills, California 91301

Address all correspondence and requests for reprints to: Paul A. Boepple, M.D., Reproductive Endocrine Unit, Bartlett Hall Extension 5, Massachusetts General Hospital, Fruit Street, Boston, Massachusetts 02114. E-mail: boepple.paul{at}mgh.harvard.edu

Abstract

The physical changes that herald the onset of puberty result from the combination of adrenarche and gonadarche. To examine adrenal maturation and associated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during long-term pituitary-gonadal suppression. Beginning at the mean age of 2.9 yr, dehydroepiandrosterone sulfate levels, linear growth, skeletal maturation, body mass index, and secondary sexual development were evaluated at 3- to 6-month intervals for up to 12.3 yr. In 12 of the girls, levels of dehydroepiandrosterone, androstenedione, 17-hydroxypregnenolone, and 17-hydroxyprogesterone were determined before and after acute ACTH stimulation every 6 months to investigate the maturation of adrenal steroidogenic enzyme activity.

Serum dehydroepiandrosterone sulfate levels rose progressively throughout the study. An exponential model fit the longitudinal datasets well and indicated that dehydroepiandrosterone sulfate levels increased approximately 22%/yr from the youngest age onward. Increasing activity of 17–20 lyase (CYP17) and decreasing activity of 3ß-hydroxysteroid dehydrogenase were also evident in preadrenarchal subjects. When controlled for chronological age, no significant associations were noted between weight, body mass index, or body surface area and dehydroepiandrosterone sulfate levels. However, similar analyses revealed modest correlations of both height and growth velocity with dehydroepiandrosterone sulfate levels.

Our results suggest that adrenarche is not the result of sudden rapid changes in adrenal enzyme activities or adrenal androgen concentrations; rather, adrenarche may be a gradual maturational process that begins in early childhood.

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