- Robert L Rosenfield, MD
Robert L Rosenfield, MD
- Professor Emeritus of Pediatrics and Medicine
- Pritzker School of Medicine of the University of Chicago
Adrenarche is the term for the maturational increase in adrenal androgen production, which becomes biochemically apparent at about six years of age in both girls and boys (figure 1) [1,2]. It is characterized by production of increasing amounts of weak androgens by the adrenal cortex, which contribute to the development of pubic hair. Although the clinical manifestations of adrenarche ordinarily closely follow true puberty, the two phenomena may be dissociated, as occurs in the presence of hypogonadism [3,4]. Thus, adrenarche seems to be unrelated to the pubertal maturation of the hypothalamic-pituitary-gonadal axis. Adrenarche is a unique phenomenon confined to a few higher primates [5-7]. (See 'Clinical manifestations of adrenarche' below.)
Premature adrenarche is an incomplete, benign, slowly progressive form of premature puberty that is an extreme variant of normal or nearly normal. The term is used to designate a very mild form of androgen excess, most often manifest as premature pubarche (the isolated appearance of sexual hair before the age of eight years in girls and nine years in boys). The evaluation of a child with premature adrenarche is discussed in a separate topic review. (See "Premature adrenarche".)
Adrenarche is the result of a developmental change in the pattern of adrenal secretory response to adrenocorticotropic hormone (ACTH) . During adrenarche the baseline pattern of adrenal steroid levels changes in a unique way (table 1). In the preadrenarchal child, ACTH stimulates cortisol secretion but has very little effect on 17-ketosteroid secretion. During adrenarche, 17-ketosteroid responsiveness to ACTH gradually increases in a selective manner, while cortisol responsiveness to ACTH remains unchanged (figure 2). The adrenarchal secretory pattern is characterized by disproportionate responsiveness of Δ5-steroid intermediates (17-hydroxypregnenolone and dehydroepiandrosterone, DHEA) relative to Δ4-steroid intermediates (eg, 17-hydroxyprogesterone and androstenedione) in the presence of stable responses of cortisol (figure 3) . As a result, dehydroepiandrosterone sulfate (DHEA-S) becomes the predominant 17-ketosteroid of blood and serves as a marker of adrenarche.
These adrenarchal changes are ACTH-dependent [8,9], but they are caused by changes in response to ACTH rather than a change in ACTH secretion. This pattern of steroid secretion is very different from that caused by excessive ACTH stimulation in the preadrenarchal child . After adrenarche, glucocorticoid administration suppresses adrenal androgens more easily than cortisol, providing further evidence that these hormones are differentially regulated [11,12].
Anatomic site and mechanism of biochemical changes — The zona reticularis of the adrenal cortex seems to be a major source of the adrenarchal steroids (figure 3) [3,5,13,14]. The increased synthesis of 17-hydroxypregnenolone, DHEA, and DHEA-S during adrenarche is a byproduct of ACTH stimulation of cortisol synthesis [8,9].
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