Alternatively, central precocious puberty may result from a tumor, infection, congenital abnormality, or traumatic injury affecting the hypothalamus. A number of congenital malformations, including hydrocephalus, craniostenosis, arachnoid cysts, and septo-optic dysplasia, can be associated with precocious puberty (and with sexual infantilism).
A common etiology (2% to 28%) of central precocious puberty is a hypothalamic hamartoma. It is a congenital malformation composed of a heterotopic mass of nerve tissue containing GnRH neurosecretory neurons, fiber bundles, and glial cells. It is not a true neoplasm and it generally does not change over time based on long-term follow-up studies with periodic CT or MRI scans. Hamartomas appear as isodense, abnormal fullnesses that do not enhance with contrast material. Extreme precocity (usually before 3 years of age) and the absence of tumor markers, such as β-human chorionic gonadotropin and α-fetoprotein, suggest a hamartoma (72). Hamartomas can be associated with laughing (gelastic) seizures, behavioral disturbances, mental retardation, and dysmorphic syndromes. It appears that hamartomas produce GnRH in a pulsatile manner and thus stimulate gonadotropin secretion (Fig. 29.18) (73). Precocious pubertal development can be controlled with GnRH-agonist therapy (74). Because deaths were reported
Precocious Puberty of Peripheral Origin after neurosurgical extirpation, the latter should be reserved for management of hamartomas associated with intractable seizures or hydrocephalus (75).
The efficacy of gonadotropin-releasing hormone analogues (GnRHa) in increasing adult height is undisputed only in early-onset (girls less than 6 years old) central precocious puberty (76). Concerns of weight gain and long-term decrease in bone mineral density with the use of GnRHa do not seem to be warranted. The most important clinical criterion for initiating GnRHa treatment is documented progression of pubertal development over a 3-to 6-month period. This observational period may not be necessary if the child is at or past Tanner stage 3, particularly with advanced skeletal maturation. It appears that discontinuation of GnRHa at a chronological age of about 11 years and a bone age of about 12 years is associated with maximum adult height (77–79). There are a variety of GnRHa formulations, and the choice of a particular agent depends on patient and physician preference.
In gonadotropin-independent precocious puberty, production of estrogens or androgens from the ovaries, adrenals, or rare steroid-secreting neoplasms leads to early pubertal development. Small functional ovarian cysts, typically asymptomatic, are common in children and may cause transient sexual precocity (80). Simple cysts (with a benign ultrasonographic appearance) can be observed and usually resolve over time. Of the various ovarian neoplasms that can secrete estrogens, granulosa-theca cell tumors occur most frequently but are still rare (81). Although such tumors may grow rapidly, more than two-thirds are benign.
Exposure to exogenous estrogens can mimic gonadotropin-independent precocious puberty. Ingestion of oral contraceptives, other estrogen-containing pharmaceutical agents, and estrogen-contaminated foods, and the topical use of estrogens, are implicated in cases of precocious development in infants and children. Ingestion of exogenous steroids over a considerable length of time is required to induce changes typical of complete precocious development.