The hCG-secreting tumors stimulate LH receptors and increase testosterone secretion. These tumors may be found in various places, including the pineal gland (dysgerminomas) or the liver (hepatoblastoma).
Ovarian cysts may occur once or may be recurrent. High serum estrogen values may mimic ovarian tumors. Congenital adrenal hyperplasia (CAH) is a cause of virilization in girls (see Chapter 178).
Evaluation of Sexual Precocity
The first step in evaluating sexual precocity is to determinewhich characteristics of normal puberty are apparent (seeChapter 67) and whether estrogen effects, androgen effects,or both are present (see Table 174-4). In girls the estrogeneffect manifests as breast development, uterine increase,and, eventually, menarche. Both boys and girls manifest the androgen effect as adult body odor, pubic and axillary hair,and facial skin oiliness and acne. In boys it is also importantto note whether the testes are enlarged more than 2.5 cm inlength (4 mL volume), which implies gonadarche. If the testes are not enlarged but virilization is progressing, the source of the androgens may be the adrenal glands or exogenous sources.
Laboratory evaluation includes determination of sex steroid levels (testosterone, estradiol, DHEAS [dehydroepiandrosterone sulfate], or androstenedione) and baseline gonadotropinconcentrations. The inherent nature of gonadotropin secretionis characterized by low secretory rates throughout childhoodand pulsatile secretion in adolescents and adults. If baselinegonadotropin values are elevated into the normal pubertalrange, central precocious puberty is likely. If baseline gonadotropins are low, however, no immediate conclusion may bedrawn as to GnRH-dependent versus GnRH-independentprecocious puberty. This distinction often requires the assessment of gonadotropin responsiveness to GnRH stimulation. Aprepubertal GnRH response is FSH predominant, whereas a pubertal response is more LH predominant. Thyroid hormonedetermination also is useful because severe primary hypothyroidism can cause incomplete precocious puberty. If there is a suggestion of a CNS anomaly or a tumor (CNS, hepatic, adrenal, ovarian, or testicular), MRI of the appropriate location isindicated. The diagnosis of central precocious puberty mandates that an MRI of the CNS be performed.
Long-acting, superactive analogs of GnRH (leuprolide depot, histrelin depot) are the treatment of choice for central precocious puberty. They suppress gonadotropin secretion by downregulating GnRH receptors in the pituitary gonadotropes (Table 174-5), causing gonadal secretion to revert to the prepubertal state. Boys with GnRH-independent premature Leydig cell and germ cell maturation do not respond to GnRH analogs but require treatment with an inhibitor of testosterone synthesis (e.g., ketoconazole), an antiandrogen (e.g., spironolactone), or an aromatase inhibitor (e.g., testolactone or letrozole). Patients with precocious puberty from a hormone-secreting tumor require surgical removal, if possible. The precocious puberty of the McCune-Albright syndrome is GnRH independent and unresponsive to therapy with GnRH
Autonomous ovarian cysts Medroxyprogesterone acetate Inhibition of ovarian steroidogenesis; regression of cyst (inhibition of FSH release)
McCune-Albright syndrome Medroxyprogesterone acetate* Inhibition of ovarian steroidogenesis; regression of cyst (inhibition of FSH release)
Boys Testolactone* Inhibition of P-450 aromatase; blocks estrogen synthesis