SAN FRANCISCO – You have a female patient come in with apparent breast development but no dark pubic hair – and she’s 7 years old. Is it a case of early puberty, a warning sign to test for possible conditions, or an unremarkable departure from typical development that does not require any intervention?
The answer to situations such as these varies, explained Dennis Styne, MD, professor of pediatrics, and Yocha Dehe Endowed Chair in Pediatric Endocrinology, at the University of California, Davis.
“We don’t know why puberty begins when it does even though we know many of the controlling factors,” Dr. Styne said at the annual meeting of the American Academy of Pediatrics, but it’s important to understand when “early” is so early that you should order lab evaluations, as opposed to simply letting an outlier’s body development continue as it would.
Normal puberty
Dr. Styne reviewed the Tanner stages of puberty for girls’ breast and pubic hair development and boys’ genital and pubic hair development, noting that the classic lower ages of pubertal onset are age 8 years in girls and 9 years in boys. Yet the normal curve may actually start earlier than those ages for U.S. girls, he noted. He shared the results of a 1997 Pediatrics study of 17,077 girls, in which by age 7 years, more than a quarter of black girls (27%) and 7% of white girls had reached at least Tanner stage 2. At age 8, nearly half of black girls (48%) and 15% of white girls had reached at least stage 2 (Pediatrics. 1997 Apr;99[4]:505-12).
Further, breast development, menarche, and early pubic hair development (pubarche) all occur earlier with increased body mass index, which has been increasing among children overall. Another study identified earlier breast development without increased body mass index: Stage 2 development occurred an average 10 months earlier in girls in 2006 than in 1991, regardless of BMI, even though no difference in LH or FSH levels occurred at these ages and estradiol level was even lower. The authors of that Danish study concluded some other factors besides pubertal hormones had to account for the increasingly earlier breast development in girls. Endocrine-disrupting chemicals are a possible cause.
Similarly, puberty in boys is occurring a bit earlier, but less dramatically so: A 2012 study of 4,131 boys found that 5.75% of black boys, 0.54% of white boys, and 1.16% of Hispanic boys had stage 2 pubic hair development by age 6. Meanwhile, 10.9% of black boys, 2% of white boys, and 2.5% of Hispanic boys began puberty with stage 2 pubic hair development at age 8 (Pediatrics 2012;130:e1058-68).
But the boys differ in one key way from the girls: Boys with obesity tend to begin puberty later than those with normal or overweight BMIs, even though overweight boys begin puberty earlier than those with normal weights.
This leaves age 8 years as a normal age to begin puberty in boys but leaves the ages for girls’ start less certain – perhaps 7 years for white girls and 6 years for black girls – but still controversial.
When to be concerned
Various neurotransmitters in the central nervous system control puberty by suppression during childhood, until a trigger for onset occurs that remains mysterious. But gene mutations, such as MKRN3 in girls, as well as brain tumors or trauma, can remove that disinhibition, prompting further investigation. Brain tumors causing precocious puberty are more common in boys than girls.
Rapid growth and bone age advancement, elevated serum levels of sex steroids, and breast development in girls could all indicate precocious puberty. If these signs are accompanied by a rise in gonadotropin values to pubertal levels, early central precocious puberty, which follows the normal course of puberty except that it is earlier, is likely.
With both sex steroids and gonadotropins in the pubertal range, a GnRH agonist could be used to control gonadal steroid production and stop bone age advancement, allowing children to reach a greater adult height if started before age 6 years. If the early puberty is slowly progressing and more subtle, no treatment at all may be necessary if there are no pathologic findings.
Without proper testing, however, a physician might as well be guessing at the cause of the early development.
“You need a highly sensitive assay, and you need pediatric standards, so you’ll probably have to send blood samples out to a national laboratory,” Dr. Styne said.
If sex hormones are being secreted at a higher rate with suppression of gonadotropins, the source is most likely autonomous secretion by the gonads or the adrenal glands.
“If you see a boy with precious puberty, with testes that are not as big as they should be for the pubertal testosterone levels, it could be that the source is the adrenal glands,” Dr. Styne said.
Meanwhile, about 75% of boys will have gynecomastia to some degree during puberty, likely because of a subtle early pubertal imbalance between estrogen and testosterone, Dr. Styne said. The condition usually regresses, but “if it doesn’t regress, there’s a chance scar tissue will develop and remain, leading to the need for surgical correction. Klinefelter syndrome must be ruled out in cases of gynecomastia or, alternatively, rarer cases of disorders of sexual development.
Dr. Styne reported that he had no relevant financial disclosures.