General Medical Information

Initiation of Adrenarche

Sander S. Shapiro and Joel S. Krasnow

Adrenarche refers to the process of adrenal gland secretion. At approximately 3 years of age, the zona reticularis begins to form. As that zone enlarges, changes in its capacity for steroid production result in increased secretion of androgens, principally dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). A rise in plasma DHEAS is first detectable at about 7 years and reaches adult levels at about 15 years of age. During this period, plasma DHEAS levels rise as much as 20-fold in both sexes. The increased production of adrenal androgens results in the development of pubic and axillary hair and contributes to the development of acne in both sexes. Adrenal androgens also contribute to advancing bone age and linear growth. Individuals who experience premature adrenarche will have a diminished adult height, because the effect of androgens on bone maturation is considerably greater than on skeletal growth.

The factors that regulate zona reticularis steroid output are not well established. The increase in androgen synthesis during adrenarche occurs in the absence of any detectable change in adrenocorticotropic hormone or cortisol secretion. A corticotropin androgen-stimulating hormone has been postulated as the agent responsible for adrenarche, but to date no such molecule has been positively identified. The onset of adrenarche typically precedes any rise in gonadotropins or change in growth rate. For this reason, the initiation of adrenal androgen production has been postulated as playing a role in the onset of puberty. Although the initiating factors in both adrenarche and gonadal puberty remain unknown, considerable experimental evidence supports a lack of association between the two processes. This evidence originates primarily from studies of patients with gonadal dysgenesis or isolated gonadotropin deficiency who almost universally experience normal adrenarche. Moreover, patients with true precocious puberty experience gonadal puberty before adrenarche. It also has been observed that children with chronic adrenal insufficiency, who consequently have deficient adrenal androgen secretion, will progress through puberty normally while receiving replacement doses of only glucocorticoids and mineralocorticoids.