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Precocious Puberty: To Treat or Not to Treat?

Erik L. Goldman, New York Bureau
Originally published in Pediatric News 33(3):49, 1999

MIAMI BEACH — Early onset of puberty can be alarming to parents, but it does not always require medical intervention, Dr. Gary D. Berkovitz said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

It does, however, require careful evaluation to determine whether the emerging pubertal features reflect a central process driven by hypothalamic and pituitary factors or whether the problem is peripheral, reflecting abnormally elevated sex steroid hormones but no hypothalamic-pituitary axis aberrations.

Central precocious puberty usually requires treatment with GnRH analogues. In some cases, peripheral precocious puberty needs nothing more than close observation, said Dr. Berkovitz, director of department of pediatric endocrinology at the university.

What is early onset of puberty? It’s a critical question, and the answer may surprise some parents. Until recently, endocrinologists considered the lower limit of normal to be 8 years old for onset of breast budding in girls and 9.5 years for pubic-axillary hair in boys.

But a recent study involving 17,077 patients in 225 pediatric practices across the nation indicated that age 7 is a more realistic cut-off for girls, especially African Americans.

In this massive cohort, 27.7% of African American girls and 6.7% of white girls had signs of breast budding by age 7. By age 8, 48.3% of African Americans and 14.7% of white girls had breast buds and/or pubic hair (Pediatrics 99[4]:505-12, 1997).

“For African American girls under 7 [years], you should watch them closely, and between 7 and 8, use good clinical judgment. Girls who start puberty early often have a slow progression through puberty,” he said. “In a lot of these cases, there’s a family history. The mothers had a similar early onset.”

If limited breast development under age 7 (premature thelarche) is the only pubertal sign—no pubic hair, menses, or accelerated growth—extensive endocrinologic evaluation is rarely needed, even if the child is very young.

Dr. Berkovitz recently assessed a 19-month-old African American girl with Tanner stage II breasts—elevation of breast and papillae with enlargement of areola diameter—but no other pubertal signs. He opted for close follow-up only. A watch-and-wait approach is also appropriate for young boys with isolated, sparse pubic or axillary hair (premature adrenarche) but no other pubertal signs.

In true precocious puberty, breast budding or pubic hair development is accompanied by accelerated growth, advancement of bone age, and adult genital features. He described a 10-month-old boy who had pubic hair at 6 months; showed abnormally rapid growth; and had a matured, 8-cm penis. Cases like this require more intensive assessment.

The initial work-up must include baseline gonadotropin levels (LH and FSH), gonadal sex steroids (testosterone, estradiol, and androstenedione), and adrenal steroids (17a-hydroxyprogesterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate). Since there can be marked interlaboratory variation in these measurements, it’s important to know the normative values used by your lab.

If all three hormone classes are at pubertal levels, there is an underlying central process at work. Hypothalamic-pituitary overactivity may be idiopathic, especially in girls but also may reflect CNS tumors, such as hamartomas, astrocytomas, or gliomas; injuries such as head trauma, meningitis, or encephalitis; or primary hypothyroidism. Dr. Berkovitz strongly recommended ordering a brain MRI to rule out neoplasia in these patients.

Regardless of etiology, central precocious puberty requires therapy. If left unchecked, bone maturation will advance ahead of linear growth, with stunting as the ultimate result. Further, a large disjunct among sexual maturity, chronologic age, and psychological development can be detrimental to the child and distressing for parents.

GnRH analogues like leuprolide acetate, which can be given intramuscularly every 4 weeks and continued until the child reaches a more normal pubertal age, are the treatment of choice. In normal puberty, the pituitary releases GnRH in pulses. Analogue injection creates a constant, elevated blood level that tricks the pituitary into shutting off synthesis of the actual hormone.

If gonadotropin levels are prepubertal, but gonadal and adrenal hormones are high, the problem is peripheral. Somewhere in the child’s body, there is a non-CNS-governed source of sex hormones. Think “tumor” and consider CT, ultrasound, and other advanced diagnostics.

In girls, small ovarian cysts, ectopic HCG tumors, and feminizing adrenal tumors are the most common causes. Some of these lesions should be excised while others can be left alone; GnRH analogue treatment is not necessary.

For boys, peripheral precocious puberty may reflect congenital adrenal hyperplasia, testicular tumors, ectopic HCG tumors, or premature Leydig’s cell maturation. Management must be determined by the nature of the underlying problem. GnRH analogue therapy is not appropriate for children with peripheral precocious development.

If the initial hormone profile doesn’t fall into either of the two general patterns of central or peripheral, overnight sampling of blood for LH/FSH and a GnRH stimulation test can be helpful. This involves intravenous infusion of 30 U of GnRH gonadorelin and measuring gonadotropins at 0, 20, 40, and 60 minutes after infusion.

If the hypothalamic-pituitary axis is “revved”—pubertal—there will be a massive surge in gonadotropin levels following infusion. If the CNS is prepubertal, there will be a slight gonadotropin increase “but nothing like what you see with a precocious pubertal pituitary.”