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Symptoms of early, delayed puberty demand close clinical attention, in spite of shifting norms for pubertal onset

Tuesday, October 14 2008 | Comments


Evidence Grade 0 What's This?
By Yvonne Poindexter

Primary care pediatricians considering whether patients' onset of puberty is truly "too early" or "too late" should look beyond established standards and focus clearly on individual cases, urged Dr. Paul Boepple, assistant professor of pediatrics at Harvard Medical School and a member of both the pediatric and reproductive endocrine units of Boston's Massachusetts General Hospital.

Traditionally, precocious puberty has been defined as onset of puberty before age 8 in girls and age 9 in boys. But what constitutes early puberty has become "a bit of a moving target," given recent studies that have raised questions about the average onset of puberty, according to Dr. Boepple. Evidence suggests that girls, in particular, are maturing earlier than their counterparts in the past. For example, analyses from 2 representative samples of girls in the United States published in 2003 suggested a drop of about 2.5 months in the average age of menarche during the time period between 1963-1970 and 1988-1994.

"Our older notions may need to be updated," said Dr. Boepple. In all cases of suspected precocious puberty, a complete history and physical exam should precede biochemical tests and imaging, he added. For example, a magnetic resonance imaging scan and ultrasound may be unnecessary for a 6-year-old girl with some breast development, particularly if development after the initial visit progresses slowly. In the initial exam, it is also essential to distinguish glandular breast tissue from fat, which can mimic true breast tissue. Physicians must also remember that race and ethnicity may influence the average age of onset of puberty. A study of 17,000 girls by the PROS network of 1,500 pediatricians nationwide suggests that breast development is normal in white girls aged as young as 7 years and in black girls aged as young as 6 years, Dr. Boepple noted.

Most patients presenting with signs of early puberty have idiopathic central precocious puberty (CPP), indicating normal endocrine processes with early onset. "The great majority do not have any underlying pathology," said Dr. Boepple, "but every once in awhile, [what pediatricians see] is not just a case of a healthy, normal kid developing early."

To detect these cases, primary care physicians should screen children with "clinical red flags" in mind. One red flag is simply male gender. Boys are much more likely than girls to develop central nervous system (CNS) lesions, such as a human chorionic gonadotropin-secreting tumor, which could mimic symptoms of precocious puberty.

"A boy with precocious puberty warrants your close attention," stressed Dr. Boepple.

In both boys and girls, neurogenic signs or symptoms such as headaches and visual disturbances are also red flags, and can be indicative of a CNS lesion.

If onset of puberty is very early, clinicians should also be wary of underlying pathology. A "related corollary," explained Dr. Boepple, is a case in which the pace of progression of pubertal symptoms is accelerated. "If there are not 2 years between the onset of breast development and menarche, but 2 months, that should get your attention," he said.

Such a quick progression could be indicative of an ovarian or testicular tumor, for example.

Other red flags to consider include abdominal pain, which could indicate the presence of a tumor, and syndromic features such as café au lait spots, which could suggest polyostotic fibrous dysplasia (McCune-Albright syndrome).

In considering treatment for CPP, it is important to remember that normal puberty results from the release of gonadotropin-releasing hormone (GnRH), and that CPP results from the same hormonal response. "It makes sense then, that treatment to essentially turn off GnRH is going to be effective," Dr. Boepple said, adding that treatment with GnRH analogs such as leuprolide acetate and histrelin acetate are "quite safe."

However, not every case of CPP needs to be treated, cautioned Dr. Boepple. GnRH analogs have their downside, and evidence is not conclusive regarding their effect on adult height and bone density. In addition, clinicians should be careful to diagnose unsustained or slowly progressing puberty correctly, because it typically does not warrant treatment. Before considering therapy, the clinician should ensure that sexual maturation is continually progressive.

"Time becomes a very important tool," said Dr. Boepple. On the other end of the spectrum, most cases of delayed puberty--like early puberty--are likely "just the end of the bell curve," said Dr. Boepple.  It is important not to overlook warning signs of underlying conditions that should be diagnosed and treated.

For both boys and girls with signs and symptoms of delayed puberty, close attention should be paid to neurologic symptoms, including sense of smell--which could be related to Kallman's syndrome in boys--as well as gastrointestinal symptoms to explore underlying medical problems. Celiac disease, for example, may lead to delayed puberty.

With delayed puberty, it is girls, not boys, presenting with symptoms who warrant physicians' close attention.

"Constitutional delay is rare among girls, so keep your antennae up for possible underlying causes," urged Dr. Boepple.

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