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In Boys with Abnormal Developmental Tempo, Maturation of the Skeleton and the Hypothalamic-Pituitary-Gonadal Axis Remains Synchronous

Developmental Endocrinology Branch (A.F.-C., E.W.L., K.M.B., M.C., J.B.) and Warren Grant Magnuson Clinical Center and the Pediatric Reproductive Endocrinology Branch (D.P.M.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and Eli Lilly and Company (G.B.C.), Indianapolis, Indiana 46285

Address all correspondence and requests for reprints to: Armando Flor-Cisneros, M.D., Building 10 RM 10N262, 10 Center Drive MSC 1862, Bethesda, Maryland 20892-1862. E-mail: flora{at}mail.nih.gov.

The primary mechanism that initiates puberty is unknown. One possible clue is that pubertal maturation often parallels skeletal maturation. Conditions that delay skeletal maturation also tend to delay the onset of puberty, whereas conditions that accelerate skeletal maturation tend to hasten the onset of puberty. To examine this relationship, we studied boys with congenital adrenal hyperplasia (n = 13) and familial male-limited precocious puberty (n = 22), two conditions that accelerate maturational tempo, and boys with idiopathic short stature (n = 18) in which maturational tempo is sometimes delayed.

In all three conditions, the onset of central puberty generally occurred at an abnormal chronological age but a normal bone age. Boys with the greatest skeletal advancement began central puberty at the earliest age, whereas boys with the greatest skeletal delay began puberty at the latest age. Furthermore, the magnitude of the skeletal advancement or delay matched the magnitude of the pubertal advancement or delay. This synchrony between skeletal maturation and hypothalamic-pituitary-gonadal axis maturation was observed among patients within each condition and also between conditions. In contrast, the maturation of the hypothalamic-pituitary-gonadal axis did not remain synchronous with other maturational processes including weight, height, or body mass index.

We conclude that in boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous. This synchrony is consistent with the hypothesis that in boys, skeletal maturation influences hypothalamic-pituitary-gonadal axis maturation.

D.P.M. and J.B. are commissioned officers in the United States Public Health Service.

Abbreviations: BMI, Body mass index; CAH, congenital adrenal hyperplasia; FMPP, familial male-limited precocious puberty; HPG, hypothalamic-pituitary-gonadal; ISS, idiopathic short stature.

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