Between 6 and 8 years of age, while cortisol concentrations and production rates remain constant, urinary excretion and circulating concentrations of DHA, DHAS, and other adrenal androgens increase. These hormonal changes, which comprise the adrenarche, are accompanied by the appearance of axillary and pubic hair and a transient acceleration of linear growth and bone maturation. Increased adrenarchal concentrations of adrenal androgens may also contribute to the observed developmental decrease in concentration of sex hormone-binding globulin and increase in bioavailable testosterone which occurs in preadolescent boys. It is not known if extra-adrenal factors, intra-adrenal factors, or a combination of both are responsible for the occurrence of adrenarche. However, known hormones, such as ACTH, prolactin, gonadotropins, and estrogens do not appear to cause the adrenarche. The existence of a relationship between adrenarche and puberty has been suggested, partly because increased concentrations of adrenal androgens in under-treated congenital adrenal hyperplasia have been associated with cases of true precocious puberty in boys. However, there is evidence against a causal relationship, including the observation that children with treated primary adrenal insufficiency enter puberty normally. Adrenarche can cause a transient acceleration of growth, increase sebum production, and serve as a permissive factor in male puberty, but does not appear to be necessary for the initiation of puberty. A clinical variant of adrenarche is premature adrenarche, which is a common cause of premature appearance of pubic hair (pubarche). It does not usually result in the alteration of subsequent puberty, but must be differentiated from congenital adrenal hyperplasia and adrenal and gonadal tumors.