Mullerian agenesis

BALTIMORE -- If you don't particularly like evaluating the 17-year-old who has not reached menarche yet, refer her to an expert, Dr. Leo Plouffe Jr. advised.

Pubertal development disorders are so rare that "if you're not going to spend the time, you won't go broke not seeing those patients, so just refer them," Dr. Plouffe said at a reproductive endocrinology meeting sponsored by Johns Hopkins University.

Gynecologists often are the first to make a diagnosis of delayed puberty because many times it goes unrecognized by parents and even pediatricians. Still, for many gynecologists, recalling the basic physiology of puberty presents the major stumbling block.

"It wasn't the most thrilling part of our medical school days and so some of us didn't pay too much attention to it. I think the lack of a full grasp [of this] is what trips us up when it comes to working up patients with pubertal disorders," said Dr. Plouffe, medical director of women's health and reproductive medicine at Eli Lilly & Co., Indianapolis.

But if physicians do decide to manage such patients, here's what Dr. Plouffe said they need to know:

The great majority of children will progress through the very orderly and classic sequence from thelarche to adrenarche and menarche with no problems. Only about 5% of females run into trouble, developing either too early or too late. A girl who has had no sign of development by age 13 warrants an evaluation.

The key thing to remember about the sequence is that about 15% of girls will develop pubic hair before they develop breasts.

There's also an expected course of timing between each of the stages.

Axillary hair usually appears 1 year after the development of pubic hair, but more important is the timing of menarche, which usually occurs around age 12.5 but can start anywhere from age 10 to age 15. Some experts say it can be normal to start as late as age 16, but "given that the age of onset of menarche has become younger and younger, I feel much more comfortable today saying it should be age 15," Dr. Plouffe said.

If menarche starts any later, it warrants a workup, he advised.

Importantly, menarche should occur within 3 years of the onset of puberty. So the child who started developing breasts and pubic hair at age 8 and who now has no sign of her period at age 12 is outside the normal window of timing and merits evaluation despite her relatively young age. In this child, "don't wait until she's age 15 to investigate delayed menarche," he said.

Menarche should also happen within 12 months of the peak growth velocity. During the peak growth velocity, girls will grow 9-10 cm in a year; this usually occurs around age 11.

Pediatricians who see these kids regularly are in the best position to detect such growth spurts. Gynecologists may not think about charting growth so closely. To do it properly "you can't depend on [the height gauges] on the scale," he said. They all tend to vary by as much as an inch. Fixed wall charts or rulers are best.

"At no time, under no circumstances, is menarche the first sign of pubertal development. So any time you get menarche as the first sign of puberty at any age, you need a workup," he added.

Menarche should also occur within Tanner stage 4, defined as the projection of the areola and papilla to form a secondary mound above the level of the breast and adult-type pubic hair covering a smaller-than-adult-sized area without extension to the thighs.

Beware of applying Tanner staging criteria intuitively As ubiquitous as Tanner staging is in textbooks, it's not an easy thing to do. A survey of pediatricians indicated that 30% were totally inept at Tanner staging, 20% were fair, and 50% were acceptably accurate. "The ability to use this tool] is not something that you're born with. You have to learn it," Dr. Plouffe said.

Nor is Tanner staging necessarily appropriate for all female populations. The progression from Tanner stage 1 to stage 3 appears to occur much more quickly in black girls than in white girls.

Precocious puberty is any sign of development before age 8, according to many textbooks. But in surveys of African American girls, 25%-50% had the onset of adrenarche at age 6. Breast development doesn't begin among these girls until age 8.

For children whose development appears to be delayed, the physician needs to assess whether there is any sign of development. If not, do a physical exam to exclude any syndromic features.

Provided that syndromes can be ruled out, do a serum FSH test. If the serum FSH level is high, order a karyotype. If the serum FSH level is low or normal, do an endocrine blood test.

"There are very few things in medicine that are this straightforward," he said.

If the FSH level is high, it means the patient is hypergonadotropic, indicating gonadal failure including gonadal dysgenesis.

If the FSH is low, the patient is hypogonadotropic, reflecting a dysfunction of the GnRH/FSH/LH axis.

If the pubertal delay appears to be isolated, in which case there may be breast growth but no pubic hair growth or vice versa, consider disorders such as the congenital absence of breast tissue, mullerian agenesis, or a transverse vaginal septum.

You need to perform an external genital exam, but "you don't need a speculum exam in these kids. That is not appropriate" during the initial workup.

In most cases, once the correct diagnosis has been made, the patient can embark on a course of treatment to induce puberty. There is evidence that if a patient can benefit from growth hormone, the earlier it's started the more effective it will be. Likewise, starting estrogen therapy earlier rather than later allows for lower dosing. "That's the big buzz right now in adolescent gynecology and endocrinology," he said.

"Simple steps will get you a long way and don't hesitate to consult and refer these patients if you don't know what you're doing," Dr. Plouffe concluded.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group