|
Precocious puberty is onset of sexual maturation before age 8 in girls or age 9 in boys. Diagnosis is by comparison with population standards, x-rays of the left hand and wrist to assess skeletal maturation and check for accelerated bone growth, and measurement of serum levels of gonadotropins and gonadal and adrenal steroids. Treatment depends on the cause.
The definition of precocious puberty depends on reliable population standards for onset of puberty (ie, when pubertal milestones occur); because onset seems to be occurring earlier in the US, these standards are being reevaluated. Almost 8 to 10% of white girls, almost 30% of black girls, and an intermediate percentage of Hispanic girls reach early puberty at age 8. The lower limit of normal puberty may be 7 yr for white girls and 6 yr for black girls. The mean age for early breast development is about 10 yr for white girls and 9 yr for black girls (range 8 to 13 yr). The mean age for pubic hair growth is 9 to 10.5 yr for both groups. These findings imply that guidelines for evaluating disorders that cause precocious puberty can be interpreted more leniently if children are otherwise healthy and are not at risk of not reaching their full adult height potential.
In girls, the first pubertal milestone is typically breast development (thelarche), followed soon after by appearance of pubic hair (pubarche) and axillary hair and later by the first menstrual period (menarche). In boys, the first pubertal milestone is typically testicular growth, followed by penile growth and appearance of pubic and axillary hair. In both sexes, appearance of pubic and axillary hair is called adrenarche.
Precocious puberty can be divided into 2 types:
GnRH-dependent precocious puberty is 5 to 10 times more frequent in girls; in boys, GnRH-dependent and GnRH-independent precocious puberty occur with similar frequency. In GnRH-dependent precocious puberty, the hypothalamic-pituitary axis is activated, resulting in enlargement and maturation of the gonads, development of secondary sexual characteristics, and oogenesis or spermatogenesis. In GnRH-independent precocious puberty, secondary sexual characteristics result from high circulating levels of estrogens or androgens, without activation of the hypothalamic-pituitary axis.
Precocious puberty may also be classified by whether gonadarche or adrenarche occurs. In girls, gonadarche includes breast development, change in body habitus, growth of the uterus, and eventually menarche. In boys, gonadarche includes testicular enlargement; phallic growth; the initial appearance of pubic, facial, and axillary hair; adult body odor; and facial skin oiliness or acne. Adrenarche for both girls and boys involves the development of body hair, body odor, and acne.
Premature appearance of only one specific pubertal milestone is generally considered a benign variant of development. Examples are precocious appearance of pubic and axillary hair before age 8 in girls and age 9 in boys, and precocious onset of breast development before age 8 in girls.
Etiology
GnRH-dependent precocious puberty
In most affected girls ≥ 4 yr, a specific cause cannot be identified. However, many girls < 4 yr have a CNS lesion. Most (60%) affected boys have an identifiable underlying lesion. Such lesions include intracranial tumors, especially of the hypothalamus (hamartoma, rarely craniopharyngioma) or pineal gland region (teratoma, pinealoma). Neurofibromatosis and a few other rare disorders have also been linked to precocious puberty.
GnRH-independent precocious puberty
Follicular ovarian cysts cause most cases; other causes include granulosa-theca cell tumors, adrenal enzyme defects, and McCune-Albright syndrome (a triad of follicular cysts, polyostotic fibrous dysplasia, and café-au-lait spots). Causes of GnRH-independent precocious puberty in boys include certain enzyme defects, familial male gonadotropin-independent precocity (due to an activating mutation of the gene for luteinizing hormone [LH] receptors), testosterone-producing testicular tumors, and occasionally McCune-Albright syndrome.
Rarely in girls and boys, puberty results from pituitary adenomas (hamartomas) that secrete gonadotropins.
Symptoms and Signs
In girls, breasts develop, and pubic hair, axillary hair, or both appear. Girls may begin to menstruate. In boys, facial, axillary, and pubic hair appears and the penis grows, with or without enlargement of testes. Body odor, acne, and behavior changes may develop in either sex. Height gain is initially rapid in both sexes, but premature closure of the epiphyses results in short adult stature. Ovarian or testicular enlargement occurs in precocious puberty but is usually absent in isolated precocious adrenarche.
Diagnosis
Diagnosis is clinical. X-rays of the left hand and wrist are done to check for accelerated skeletal maturation as a result of sex hormone effect. Unless history and examination suggest an abnormality, no further evaluation is required for children with pubertal milestones that are within 1 yr of population standards. Girls and boys with precocious adrenarche and girls with precocious thelarche also do not require further evaluation as long as x-rays confirm that skeletal maturation is not accelerated.
When further evaluation is necessary, the following serum hormones may be measured: β-human chorionic gonadotropin, estradiol, testosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, LH, follicle-stimulating hormone (FSH), and prolactin. Pelvic and adrenal ultrasonography and MRI or CT of the brain may be done.
A GnRH stimulation test (see Endocrine Disorders in Children: Diagnosis) confirms a diagnosis of GnRH-independent precocious puberty when gonadotropin responses to exogenous GnRH are prepubertal in boys or girls with no tumor or other obvious cause of early sexual development. If the response is pubertal, CNS lesions must be excluded.
Treatment
If pubertal milestones are within 1 yr of population standards, reassurance and regular reexamination are sufficient. Treatment is not needed for premature adrenarche or thelarche, but regular reexamination is warranted to check for later development of precocious puberty. For GnRH-dependent precocious puberty, pituitary LH and FSH secretion can be suppressed until normal puberty begins with the GnRH agonist leuprolide acetate 0.2 to 0.3 mg/kg (minimum, 7.5 mg) IM q 4 wk. Responses to treatment must be monitored, and drug dosages modified accordingly.
In girls with McCune-Albright syndrome, testolactone, an aromatase inhibitor, reduces serum estradiol and effectively treats affected girls; alternatively, tamoxifen, an estrogen antagonist, may be beneficial.
If GnRH-independent precocious puberty in boys is due to familial male gonadotropin-independent precocity or McCune-Albright syndrome, androgen antagonists (eg, spironolactone) ameliorate the effects of excess androgen. The antifungal drug ketoconazole reduces testosterone in boys with familial male gonadotropin-independent precocity.
If GnRH-independent precocious puberty is due to a hormone-producing tumor (eg, granulosa-theca cell tumors in girls, testicular tumors in boys), the tumor should be excised. However, girls require extended follow-up to check for recurrence in the contralateral ovary.
Last full review/revision May 2009 by Nicholas Jospe, MD
|
