Questions surround using GH in transition patients

Recombinant human growth hormone is not a fountain of youth and is not recommended for healthy aging outside the clinical trial setting.

Issue: May 2007

SEATTLE — Experts discussed the pros and cons of recombinant human growth hormone treatment in patients beyond childhood at the American Association of Clinical Endocrinologists 16th Annual Meeting and Clinical Congress.

It is not a fountain of youth to be used to counter the changes of normal aging, but instead should be limited to use in hypopituitarism and specific other endocrine disorders in adults, children and patients in the transition stage, according to researchers.

“We believe that a hormone for which nothing else will substitute in childhood does not lose its unique effects as soon as linear growth ceases. It continues to have important functions when used to replace bona fide growth hormone deficiency,” said George R. Merriam, MD, physician at the VA Puget Sound Health Care System and professor of medicine at the University of Washington, who explained that the most widespread off-label use of GH is by people who want to stop the aging clock. He strongly advised against its use for this indication.

“In contrast to adult GH deficiency, there is still no solid evidence that GH supplementation in otherwise normal older adults provides meaningful clinical benefits, and adverse events can be frequent,” Merriam and colleague David M. Cook, MD, chief of endocrinology at Oregon Health and Science University, wrote in their syllabus.

In the transition patient

GH can, however, be extremely useful in the transition patient, which is generally defined as a patient who was treated with GH during childhood but has since entered his late teens or early 20s, thus, in transition between pediatric and adult indications.

Many questions surround GH in the transition patient, such as when to stop treatment, how much to dose and what the best treatment is. Cook suggested a few guidelines to help endocrinologists who treat transition patients.

All patients should be reassessed for persistent GH deficiency (GHD) when they reach their final height, according to Cook. Physicians should wait one month after stopping GH to obtain an insulin-like growth factor I (IGF-I) sample. In patients with an organic cause, such as a genetic syndrome or pituitary tumor, a low test value confirms persistence of GHD. In patients with isolated childhood GHD and no other pituitary deficits, then GH provocative tests may also need to be repeated.

While some suggest a two-year holiday from GH therapy in these patients before starting again, Cook said this can cause patients to gain body fat and lose muscle mass, and may impair their ability to reach normal bone mass. Patients aged 25 to 30 are still in the accrual phase of bone mineral deposition, he said, and this process can be interrupted with a longer duration of discontinuation.

With GH dosing, the general rule has been to titrate doses independent of weight, according to Cook and Merriam. Older patients usually receive lower doses and younger patients receive higher doses. Cook said doses are increased at monthly intervals in 0.2-mg/day increments until a target normal IGF-I level is reached. His rule of thumb is to use doses in the range of 25 mcg to 30 mcg in the transition patient. Too high a dose can lead to acromegaly.

Overall, follow-up is essential from childhood into the transition period to adulthood, Cook said. These signs of persistent GHD can otherwise be missed.

Other concerns

Previous data suggest an increased risk for cancer with GH treatment, including colorectal, breast and prostate cancers. However, Merriam said that cancer trials produced mixed data and all those suggesting increased risk had studied patients treated as children with the older extracted pituitary growth hormone. By contrast there is no evidence of increased cancer risk in patients treated as adults with recombinant synthetic GH, although the base of experience is shorter.

According to Cook, no evidence points to an increased risk for recurrence of the original pituitary tumor with GH replacement into the normal ranges. Currently, the general consensus is to withhold GH in patients with active cancer or where there is any doubt. – by Katie Kalvaitis

For more information:
Cook DM and Merriam GR. Growth hormone in adults and adolescents: pros and cons. Presented at: The American Association of Clinical Endocrinologists 16th Annual Meeting and Clinical Congress. April 11-15, 2007; Seattle.