Precocious puberty is the onset of secondary sexual charac-teristics prior to the age 6 in black girls and age 7 in white girls.
Precocious puberty is caused by either GnRH-dependentor GnRH-independent sex hormone production (Box 34.1).GnRH-dependent, or true (central) precocious puberty, develops secondary to early activation of the hypothalamic– pituitary–gonadal axis. The most common causes are idiopathic; other causes include infection, inflammation, or injury of the central nervous system. In idiopathic pre-cocious puberty, the arcuate nucleus in the hypothalamus is prematurely activated. This causes early sexual maturation with early reproductive capability. The elevated estrogen levels affect the skeleton, resulting in short stature in adult-hood secondary to premature closure of the epiphyseal plates. These individuals are at risk for sexual abuse and have psychosocial problems related to their early sexual develop-ment. Occasionally, GnRH-dependent precocious puberty results from neoplasms of the hypothalamic–pituitary stalk. In this situation, although sexual development begins early, the rate of sexual development is slower than usual. Transient inflammatory conditions of the hypothalamus may also result in GnRH-dependent precocious puberty; however, sexual development may begin and end abruptly. Laboratory studies show either an appropriate rise in go-nadotropins or a steady gonadotropin level in the prepuber-tal range.
GnRH-independent sex hormone production, or precocious pseudopuberty (peripheral), results from sex hormone production (androgens or estrogens) independent of hypothalamic–pituitary stimulation. This condition can be caused by ovarian cystsor tumors, McCune–Albright syndrome, adrenal tumors, or iatrogenic causes. Some tumors, such as granulosa cell tumors, teratoma, or dysgerminomata, directly secrete androgen. Physical examination usually reveals a palpable pelvic mass and leads to further evaluation/imaging studies.
McCune–Albright syndrome (polyostotic fibrous dysplasia) is characterized by multiple bone fractures, café-au-lait spots, and precocious puberty. Premature menarche can be the first sign of the syndrome.
The syndrome is thought to result from a defect in cellular regulation with a mutation in the alpha subunit of the G protein that stimulates cAMP formation, which causes affected tissues to function autonomously. This mutation causes the ovary to produce estrogen with-out the need for FSH, resulting in sexual precocity.
Adrenal causes of precocious puberty include adrenal tumors or enzyme-secreting defects, such as congenital adrenal hyperpla-sia (CAH). Tumors are very rare and must secrete estrogento cause early sexual maturation. The most common form of CAH, 21-hydroxylase deficiency, presents at birth with the finding of ambiguous genitalia. However, the nonclassical form, previously known as late-onset CAH, tends to present at adolescence. In this disorder, the adrenal glands are unable to produce adequate amounts of cortisol as a result of a partial block in the conversion of 17-hydroxyprogesterone to deoxycortisol. Deficiency of the 21-hydroxylase enzyme leads to a shunting away from aldosterone and cortisol production in cholesterol biosyn-thesis toward the production of androgens (testosterone and estradiol), which results in precocious adrenarche. Apathognomonic finding for 21-hydroxylase deficiency is an elevated 17-hydroxyprogesterone level. Plasma renin is also measured todetermine the amount of mineralocorticoid deficiency. Medical therapy is instituted as early as possible and is aimed at steroid/mineralocorticoid replacement, depending on the severity of the deficiency. In the nonclassical form of CAH, patients present with premature adrenarche, anovulation, and hyperandrogenism, appearing somewhat like patients with polycystic ovarian syndrome.
Iatrogenic causes such as drug ingestion must be considered in all children who present with precocious puberty.
These children may exhibit increased pigmentation of the nipples and areola of the breast secondary to ingestion of oral contraceptives, anabolic steroids, and hair or facial creams.
The main goals of treatment of precocious puberty are to ar-rest and diminish sexual maturation until a normal pubertal age, as well as to maximize adult height. Therapy for GnRH-independent precocious puberty involves administration of a GnRH agonist. Results occur rapidly and continue during the first year of treatment. Treatment for GnRH-independent precocious puberty attempts to suppress go-nadal steroidogenesis.