YOSEMITE, CALIF. — The best laboratory evidence of puberty is a test for luteinizing hormone and follicle-stimulating hormone done by immunochemiluminometric assay, Stephen M. Rosenthal, M.D., said at a pediatric conference sponsored by Symposia Medicus.
Two labs that run the tests are Esoterix Inc. and Quest Diagnostics Inc., said Dr. Rosenthal, professor of pediatrics at the University of California, San Francisco.
“If you ever order tests for LH and FSH, it's very important that you order them by immunochemiluminometric assay (ICMA), because [the tests] are able to distinguish between someone who's prepubertal and the different Tanner stages,” he said.
If you get results that are difficult to interpret, Dr. Rosenthal recommended doing a GnRH stimulation test, which is also called a luteinizing hormone releasing factor (LRF) stimulation test. This involves giving a synthetic bolus of GnRH and then measuring the patient's levels of LH, FSH, and either estradiol or testosterone.
Dr. Rosenthal noted that there have been availability problems with GnRH. If GnRH is not available, a similar test can be done with leuprolide acetate, a GnRH agonist. Guidelines for carrying out the latter test are described in the following reference: J. Clin. Endocrinol. Metab. 1994;78:30–5.
“If you give an injection of synthetic GnRH [or agonist] to somebody who's in puberty, their own pituitary gland has been primed by their own GnRH; so when you give it, you're going to see a vigorous rise in LH,” he explained.
The differential diagnosis of delayed puberty is defined clinically as a girl who has no evidence of breast development by age 13 years or a boy who has no evidence of testicular enlargement by age 14 years. The following are general possibilities in this differential diagnosis:
▸ Constitutional delay in growth. Most children seen for concerns about delayed puberty will fit this category.
“This is one of those interesting scenarios where it appears that people not only grow more slowly and reach puberty more slowly, it's like there's something in their biological clock that makes them age more slowly,” Dr. Rosenthal noted. “They ultimately reach a normal adult height and full pubertal development; it just takes them longer to get there. This often runs in families. Is it possible that these kids actually age more slowly as they grow older, even as adults?” he asked. “Is there something to be learned here to give us some insight? We don't know the answer to that yet because there are so many variables as we get older that affect longevity.”
▸ Hypogonadotropic hypogonadism. In this condition, the defect is located in the hypothalamus or in the pituitary gland. The cause could be Kallmann syndrome or could be associated with other conditions including cleft palate; congenital deafness; the X-linked form of congenital adrenal hypoplasia; Prader-Willi syndrome; Laurence-Moon-Biedl syndrome; central nervous system disease; and a variety of other conditions such as hypothyroidism, poorly controlled diabetes, and anorexia nervosa.
▸ Hypergonadotropic hypogonadism. In this condition, the defect is in the testes or ovaries. Potential causes include Klinefelter's syndrome and its variants; anorchia; cryptorchidism; XY gonadal dysgenesis; Noonan's syndrome; Turner's syndrome and its variants; and XX gonadal dysgenesis.