Growth hormone-deficient young adults need larger replacement doses than older adults

Young adults who received growth hormone treatment as children for deficiencies in producing that essential hormone likely will need continued treatment for years and at higher doses than doctors now prescribe, a new multi-center North American study concludes.

Higher doses of the hormone should help protect such patients from excessive and eventually crippling declines in the density of their bones and from higher blood levels of harmful fats that could promote heart disease, researchers say. Earlier reports suggested growth hormone also helped maintain healthy muscle mass and lessened depression, a common complaint among patients.

A report on the study, conducted over two years at 12 U.S. and five Canadian medical centers, appears in the November issue of the Journal of Clinical Endocrinology & Metabolism.

Dr. Louis Underwood, professor of pediatrics at the University of North Carolina at Chapel Hill School of Medicine, led the research. Co-authors of the paper were Drs. Kenneth M. Attie and Joyce Baptista of Genentech Inc. of San Francisco and the Genentech Collaborative Study Group.

“We did this randomized, double-blind, placebo-controlled trial to improve our understanding of what doses we should give young adults who need treatment,” said Underwood. “We believe our findings will change clinical practice in the United States and abroad.”

Typically, doctors treat growth hormone-deficient children with hormone doses that reach a peak in late adolescence when the naturally secreted compound reaches its maximum in healthy children, he said. As patients age into adulthood, clinicians often stop treatment to determine whether there is a continued need. If so, treatment is restarted at significantly lower doses since older adults need less growth hormone and cannot tolerate it as well as children.

“Besides the placebo, which is inactive, we tested a dose of 25 micrograms per kilogram of body weight per day and also a dose that was half that large,” Underwood said. “The 25 microgram dose is about half of what is used in children.”

The medical scientists studied 39 men and 25 women, all under age 35, and looked especially at what happened to their bone mineral density, depending on whether or not they received growth hormone and how much.

“Compared with the placebo group, patients who got 12.5 micrograms showed better bone mineral density after two years,” Underwood said. “Those who received 25 micrograms per kilogram daily showed an even greater and more sustained effect.”

Both growth hormone-treated groups had similar changes in body composition at six months — decreased fat and increased lean mass — but some improvements were later lost in the lower-dose group, he said.

“A significant decrease in low-density lipoprotein cholesterol, which is believed to be bad for a person’s health, was seen only in the higher growth hormone dose group,” Underwood said. “We did not observe significant changes in quality of life or echocardiograph measures.”

Adverse effects among study groups were about the same except that the hormone-treated groups showed more swelling, a common side effect of such treatment in adults, he said.

Genentech supported the research. Collaborating institutions in the United States included Children’s Hospital Medical Center in Cincinnati, Kansas Medical Center, the Medical College of Wisconsin, the Oregon Health Sciences University, Stanford University and the universities of California at Los Angeles and Michigan. Canadian institutions included Children’s Hospital in Winnipeg, Children’s Hospital of Western Ontario, Central University Hospital in Sherbrooke, Quebec, the Research Center of Hotel-Dieu of Montreal and Central Hospital of Laval University in Ste.-Foy, Quebec.

In the 1970s, Dr. Judson J. Van Wyk, Underwood and UNC colleagues purified a compound known as IGF-1 and developed an assay for it. IGF-1, or insulin-like growth factor 1, is a growth-hormone-dependent protein that mediates many of the growth-promoting actions of growth hormone.

Now, doctors around the world monitor the effect of growth hormone therapy in hormone-deficient adults by testing their levels of IGF-1, which is made throughout the body but chiefly in the liver. The brain’s pea-sized pituitary gland produces growth hormone.