Precocious puberty can be isosexual (secondary sex characteristics of the same sex) or heterosexual (masculinization in girls and feminization in boys). The syndromes have been further subdivided into those that produce true puberty with functioning gonads and those that produce pseudopuberty, in which development of secondary sex characteristics suggests puberty but the gonads do not function. The major causes of precocious puberty are idiopathic early puberty or the hyper secretion of androgens or estrogens from hypothalamic, pituitary, adrenal, gonadal, or factitious (self-medication) sources.

Hypothalamic precocious puberty is usually associated with a tumor (e.g., a pinealoma) involving the hypothalamus or with encephalitis. The result is always an isosexual true puberty.

Pituitary precocious puberty is usually idiopathic (“constitutional”). The result is normal isosexual puberty. In girls the condition rarely may be due to Albright’s syndrome (polyostotic fibrous dysplasia). Primary pituitary tumors do not cause precocious puberty.

Gonadal precocious puberty in boys results from a Leydig cell tumor of the testis that produces testosterone. This is a pseudopuberty, since FSH is not produced and no spermatogenesis occurs. In girls, various ovarian tumors may cause pseudopuberty, which may be either isosexual or heterosexual, depending on whether the tumor secretes estrogens or androgens. Granulosa-theca cell tumors are the most frequent, although their peak incidence is not until middle age. These tumors most frequently produce estrogens. Dysgerminoma and malignant teratoma are two uncommon ovarian tumors that may produce hCG rather than the usual type of estrogens.

Adrenal precocious puberty is due to either congenital adrenal hyperplasia or adrenal tumor. In early childhood, congenital adrenal hyperplasia is more likely; if onset is in late childhood or prepubertal age, tumor is more likely. In both cases a pseudopuberty results, usually isosexual in boys and heterosexual (virilization) in girls. Congenital adrenal hyperplasia may also produce pseudohermaphroditism (simulation of male genitalia) in infant girls.

Hypothyroidism has been reported to cause rare cases of true isosexual precocious puberty in both boys and girls.

Laboratory evaluation

Laboratory evaluation depends on whether the physical examination indicates isosexual or heterosexual changes. In girls, heterosexual changes point toward congenital adrenal hyperplasia, ovarian tumor, or adrenal carcinoma. The most important test for diagnosis of congenital adrenal hyperplasia is plasma 17-hydroxyprogesterone (17-OH-P) assay. A 24-hour urine specimen for 17-ketosteroids (17-KS) is also very helpful, since the 17-KS values are elevated in 80%-85% adrenal carcinoma, frequently elevated in congenital adrenal hyperplasia, and sometimes elevated in ovarian carcinoma. If test results for congenital adrenal hyperplasia are negative, normal urine 17-KS levels point toward ovarian tumor. Ultrasound examination of the ovaries and adrenals and an overnight dexamethasone screening test for adrenal tumor are helpful. Computerized tomography (CT) of the adrenals is also possible, but some believe that CT is less successful in childhood than in adults. Isosexual changes suggest hypothalamic area tumor, constitutional precocious puberty, ovarian estrogen-secreting tumor, or hypothyroidism. Useful tests include serum thyroxine assay, ultrasound examination of the ovaries, and CT scan of the hypothalamus area. The possibility of exposure to estrogen-containing creams or other substances should also be investigated. Serum hCG levels may be elevated in the rare ovarian choriocarcinomas.

Female isosexual precocious puberty must be distinguished from isolated premature development of breasts (thelarche) or pubic hair (adrenarche). Female heterosexual precocious puberty must be distinguished from hirsutism, although this is a more common problem during and after puberty.

In boys, heterosexual precocious pseudopuberty suggests estrogen-producing tumor (testis choriocarcinoma or liver hepatoblastoma) or the pseudohermaphrodite forms of congenital adrenal hyperplasia. Tests for congenital adrenal hyperplasia plus serum hCG are necessary. Isosexual precocious puberty could be due to a hypothalamic area tumor, constitutional (idiopathic) cause, testis tumor (Leydig cell type), hypothyroidism, or congenital adrenal hyperplasia. Necessary tests include those for congenital adrenal hyperplasia and a serum thyroxine determination. If the results are negative, serum testosterone (to detect values elevated above normal puberty levels) and hypothalamic area CT scan are useful. Careful examination of the testes for tumor is necessary in all cases of male precocious puberty.