Adrenarche

Adrenarche refers to a stage of maturation of the cortex of the human adrenal glands. It typically occurs between ages 6 and 10 years and involves both structural and functional changes. Adrenarche is a process related to puberty but distinct from hypothalamic-pituitary-gonadal maturation and function.

Structural and functional changes of adrenarche
Structural changes of adrenarche include increased size and mass of the adrenal cortex, and completion of differentiation into the three zones: zona glomerulosa, zona fasciculata, and zona reticularis.

One of the primary functional changes is further differentiation of sex steroid synthesis among the three zones, so that as in adults, the zona glomerlulosa primarily produces mineralocorticoids such as aldosterone, the zona fasciculata primarily produces glucocorticoids such as cortisol, and the zona reticularis primarily produces androgens such as dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione.

The second important functional change is a steady increase over several years in the daily production of adrenal androgens. A characteristic aspect of early adrenarche is a diminished activity of 3β-hydroxysteroid dehydrogenase, the enzyme which mediates the hydroxylation of 17-hydroxypregnenolone to 17-hydroxyprogesterone, and DHEA to androstenedione. Blood levels of DHEA, androstenedione, and especially DHEAS are useful measures of adrenal maturation.

Role of adrenarche as part of puberty
An initiator of adrenarche has not yet been identified. Researchers have unsuccessfully tried to identify a new pituitary peptide, to be called "adrenal androgen stimulating hormone". Others have proposed that adrenarchal maturation is a gradual process intrinsic to the adrenal glands that has no distinct trigger. A third avenue of research is pursuing a possible relationship with either fetal or childhood body mass and related signals such as insulin and leptin. Many children born small for gestational age (SGA) because of intrauterine growth retardation (IUGR) have an earlier onset of adrenarche, which raises the possibility that timing of adrenarche may be affected by physiological programming in infancy. Adrenarche also occurs prematurely in many children who are overweight, suggesting a possible relationship with body mass or adiposity signals.

The principal physical consequences of adrenarche are androgen effects, especially pubic hair and the change of sweat composition that produces adult body odor. Increased oiliness of the skin and hair and mild acne may occur. In most boys, these changes are indistinguishable from early testicular testosterone effects occurring at the beginning of gonadal puberty. In girls, the adrenal androgens of adrenarche produce most of the early androgenic changes of puberty: pubic hair, body odor, skin oiliness, and acne. In most girls the early androgen effects coincide with, or are a few months behind, the earliest estrogenic effects of gonadal puberty (breast development and growth acceleration). As female puberty progresses, the ovaries and peripheral tissues become more important sources of androgens.

Parents and many physicians often infer (incorrectly) the onset of puberty from the first appearance of pubic hair (termed pubarche). However, the independence of adrenarche and gonadal puberty is apparent in children with atypical or abnormal development, when one process may occur without the other. For instance, adrenarche does not occur in many girls with Addison's disease, who will continue to have minimal pubic hair as puberty progresses. Conversely, girls with Turner syndrome will have normal adrenarche and normal pubic hair development, but true gonadal puberty never occurs because their ovaries are defective.

Premature adrenarche
Premature adrenarche is the most common cause of the early appearance of pubic hair ("premature pubarche") in childhood. In a large proportion of children it seems to be a variation of normal development requiring no treatment. However, there are three clinical issues related to premature adrenarche.

First, when pubic hair appears at an unusually early age in a child, premature adrenarche should be distinguished from true central precocious puberty, from congenital adrenal hyperplasia, and from androgen-producing tumors of the adrenals or gonads. Pediatric endocrinologists do this by demonstrating advanced levels of DHEAS and other adrenal androgens, with prepubertal levels of gonadotropins and gonadal sex steroids.

Second, there is some evidence that premature adrenarche may indicate that there was an abnormality of intrauterine energy environment and growth. As mentioned above, premature adrenarche occurs more often in children with intrauterine growth retardation and in overweight children. Some of these same studes have demonstrated that some girls who display premature adrenarche may continue to have excessive androgen levels in adolescence. This can result in hirsutism or menstrual irregularities due to anovulation referred to as polycystic ovary syndrome.

Third, at least one report found an increased incidence of behavior and school problems in a group of children with premature adrenarche compared with an otherwise similar control group. To date such a relationship has neither been confirmed nor explained and there are no obvious management implications.