Karla Harby

April 16, 2007

April 16, 2007 (Seattle) — Adolescents and young adults with a history of growth hormone (GH) deficiency in childhood may have below-normal levels of GH that impair their ability to build bone, as well as their quality of life. But the signs are subtle, and when GH is administered to teens or young adults, careful follow-up is essential.

David M. Cook, MD, from Oregon Health and Science University in Portland, and George R. Merriam, MD, from the Division of Metabolism, Endocrinology and Nutrition at the University of Washington in Seattle, discussed the pros and cons of GH therapy beyond childhood in a presentation here at the annual meeting and clinical congress of the American Association of Clinical Endocrinologists.

Benefits of restoring GH to normal levels in this age group (up to about the late 20s) include improvement in psychological symptoms, such as depression, inability to focus, and difficulty in school. Physical improvements include higher bone density, increased energy, and reduced body fat, particularly visceral fat. Potential adverse events include acromegalic changes.

Dr. Cook began by reviewing the natural history of pituitary tumors. Researchers report that "growth hormone did not cause a recurrence of stable pituitary tumor," Dr. Cook said. "I think we can say it's pretty safe, and all the big companies [that produce it] have concluded this also."

Nonetheless, GH receptors exist in many types of cells, including colon, breast, and lymph cells, both in their normal and their transformed, cancerous forms, Dr. Merriam said. GH is mitogenic and stimulates cancer cell growth in culture. The latency for cancers can be decades, and so GH should not be used in cancer patients. However, "there is no evidence at the moment that GH replacement within the normal range increases the risk of de novo cancer," he added.

More needs to be learned about dosing and about stimulation testing in this age group, Dr. Cook said. Stimulation testing is imperfect, so should only be used when warranted by clinical context. In trying to decide on the right dose, he said, "I try 20 to 30 µg/kg per day, and an IGF-1 [insulin-like growth factor level] that's at least above the mean." Excess GH can lead to acromegalic changes, defined as a foot or lower jaw size greater than the 97th percentile.

Dr. Cook described several of his patients in detail. "It's nice to do an MRI in these patients to see if they have something abnormal," such as the hypoplastic pituitary he showed on one MRI. After 3 years of therapy, this patient's bone density was such that she was able to ski safely.

Dr. Merriam, an expert in the study of GH as an anti-aging therapy, reminded the audience that there's a difference between being GH-deficient and being within an age-adjusted normal range. "If you're deficient, GH does a lot of good things for you, even if you're not going to get any taller," he said. But if GH is normal, adding more leads to acromegaly, he said.

He pointed out that the 1990 study that helped launch popular interest in GH for anti-aging treatment involved 21 healthy men and was neither blinded nor placebo controlled. Those authors reported no adverse effects. "Everybody who's tried to replicate this study has run into huge side effects, and use had to be cut back," Dr. Merriam said.

A 1992 initiative by the National Institute on Aging funded 7 proposals, all of which are completed, although not all have been published, Dr. Merriam said. "I've seen the results of all of them. The consensus is that [GH] increases lean body mass and reduces body fat, especially visceral fat."

But the adverse effects were such that doses had to be reduced. A recent review in the Annals of Internal Medicine (2007;146:104-115) found only small changes in body composition in healthy elderly subjects, and an increase in peripheral edema. "Currently, GH can't be recommended outside of clinical trials," Dr. Merriam said.

The moderator for this session, Jeffrey R. Garber, MD, from Harvard Medical School in Boston, Massachusetts, told Medscape: "One cannot use [growth hormone] as an anti-aging therapy, and one has to be cautious about using it if there is a history of cancer, and not use it if there is active cancer." He added that "[GH] is probably underutilized in people who have a documented hormone deficiency and grow into adulthood."

He also agreed that the signs of deficiency are subtle. "You can't diagnose this clinically; that's why it's underused. People do not look abnormal, and they need to be treated carefully." He recalled the one young man described by Dr. Cook, whose jaw grew abnormally large under therapy, then emphasized, "And that's a patient of one of the best endocrinologists in the world."

This work was independently funded. The authors report no relevant financial relationships.

AACE 16th Annual Meeting and Clinical Congress: General Session. Presented April 14, 2007.

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