- Robert L Rosenfield, MD
Robert L Rosenfield, MD
- Professor of Pediatrics and Medicine
- Pritzker School of Medicine of the University of Chicago
- Section Editors
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- National Institute of Child Health and Human Development
- Mitchell Geffner, MD
Mitchell Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
Adrenarche is the term for the maturational increase in adrenal androgen production that becomes biochemically apparent as a rise in dehydroepiandrosterone sulfate (DHEA-S) at about six years of age in both girls and boys (figure 1). It represents a gradual change in the pattern of adrenal secretory response to corticotropin (adrenocorticotropic hormone, ACTH), characterized by a disproportionate rise of 17-hydroxypregnenolone and dehydroepiandrosterone (DHEA) relative to cortisol. This change primarily occurs in the zona reticularis of the adrenal cortex, the cells of which express a unique pattern of steroidogenic enzymes that includes expression of sulfotransferase 2A1 (SULT2A1), which catalyzes the formation of DHEA-S, the major adrenarchal steroid (figure 2). (See "Normal adrenarche".)
The causes, diagnosis, and management of premature adrenarche will be reviewed here. It is useful, however, to begin with a review of definitions used to describe the various aspects of premature sexual development as they relate to adrenarche.
The definitions used to describe normal and premature puberty and pubarche are as follows:
Puberty — Puberty is the stage of development during which secondary sexual characteristics appear and there is a transition from the sexually immature to the sexually mature stage. True puberty results from activation of the hypothalamic-pituitary-gonadal (HPG) axis. Testicular enlargement is the usual first sign of gonadal activation (gonadarche) in boys, and breast development (thelarche) is the first sign in girls, with sexual hair development ordinarily occurring later. The physiology and clinical stages of puberty are discussed in a separate topic review. (See "Normal puberty".)
Premature puberty — The exact age at which puberty is abnormally early (precocious) is not well defined. In general, signs of secondary sexual development occurring before the age of eight years in girls and the age of nine years in boys are considered premature and warrant careful evaluation. This practice is supported by data in girls, though breast budding is normal during the seventh year in Black and Mexican-American girls , while good data are still lacking in boys . Gonadotropin-dependent precocious puberty (also termed “central,” “true,” “or “complete” precocity) results from activation of the normal HPG axis. Gonadotropin-independent precocious puberty (also termed “peripheral” precocious puberty) results from excess exposure to androgens or estrogens derived from the gonads, adrenal glands, exogenous sources, or ectopic production of human chorionic gonadotropin (hCG) by a tumor. (See "Definition, etiology, and evaluation of precocious puberty".)
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- Nayak S, Lee PA, Witchel SF. Variants of the type II 3beta-hydroxysteroid dehydrogenase gene in children with premature pubic hair and hyperandrogenic adolescents. Mol Genet Metab 1998; 64:184.
- Witchel SF, Lee PA, Suda-Hartman M, Hoffman EP. Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency. Biochem Mol Med 1997; 62:151.
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- Charmandari E, Kino T, Ichijo T, Chrousos GP. Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. J Clin Endocrinol Metab 2008; 93:1563.
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- Armengaud JB, Charkaluk ML, Trivin C, et al. Precocious pubarche: distinguishing late-onset congenital adrenal hyperplasia from premature adrenarche. J Clin Endocrinol Metab 2009; 94:2835.
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- Lutfallah C, Wang W, Mason JI, et al. Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 2002; 87:2611.
- Rosenfield RL, Cohen RM, Talerman A. Lipid cell tumor of the ovary in reference to adult-onset congenital adrenal hyperplasia and polycystic ovary syndrome. A case report. J Reprod Med 1987; 32:363.
- Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92:405.
- Abraham GE. Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle. J Clin Endocrinol Metab 1974; 39:340.
- Rosenfeld RS, Rosenberg BJ, Fukushima DK, Hellman L. 24-Hour secretory pattern of dehydroisoandrosterone and dehydroisoandrosterone sulfate. J Clin Endocrinol Metab 1975; 40:850.
- Balassy C, Navarro OM, Daneman A. Adrenal masses in children. Radiol Clin North Am 2011; 49:711.
- Shah RU, Lawrence C, Fickenscher KA, et al. Imaging of pediatric pelvic neoplasms. Radiol Clin North Am 2011; 49:729.
- Pascale MM, Pugeat M, Roberts M, et al. Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours. Clin Endocrinol (Oxf) 1994; 41:571.
- Sontag-Padilla LM, Dorn LD, Tissot A, et al. Executive functioning, cortisol reactivity, and symptoms of psychopathology in girls with premature adrenarche. Dev Psychopathol 2012; 24:211.
- Premature puberty
- Premature pubarche
- Premature adrenarche
- Exaggerated adrenarche
- DIFFERENTIAL DIAGNOSIS OF PREMATURE PUBARCHE
- Idiopathic premature pubarche
- Gonadotropin-dependent precocious puberty
- Virilizing disorders
- - Virilizing congenital adrenal hyperplasia
- - Related congenital ACTH-dependent forms of adrenal hyperandrogenism
- - Cushing's syndrome
- - Virilizing tumors
- Exogenous androgen exposure
- EVALUATION OF PREMATURE PUBARCHE
- History and physical examination
- Bone age
- Hormonal measurements
- ACTH stimulation test
- Dexamethasone androgen-suppression test
- MANAGEMENT OF PREMATURE ADRENARCHE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS