Endocrine Reviews Journal Article

Normal and Premature Adrenarche

July 05, 2021
 

Robert L Rosenfield
Endocrine Reviews, First published online March 31, 2021, bnab009
https://doi.org/10.1210/endrev/bnab009

Abstract

Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to adrenocorticotropin (ACTH) that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3β-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17β-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, and prolactin are related to ZR development. Adrenarchal androgens normally contribute to the onset of sexual pubic hair (pubarche) and sebaceous and apocrine gland development. Premature adrenarche causes ≥90% of premature pubarche (PP). Its cause is unknown. Affected children have a significantly increased growth rate with proportionate bone age advancement that typically does not compromise growth potential. Serum DHEAS and testosterone levels increase to levels normal for early female puberty. It is associated with mildly increased risks for obesity, insulin resistance, and possibly mood disorder and polycystic ovary syndrome. Between 5% and 10% of PP is due to virilizing disorders, which are usually characterized by more rapid advancement of pubarche and compromise of adult height potential than premature adrenarche. Most cases are due to nonclassic congenital adrenal hyperplasia. Algorithms are presented for the differential diagnosis of PP. This review highlights recent advances in molecular genetic and developmental biologic understanding of ZR development and insights into adrenarche emanating from mass spectrometric steroid assays.

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