Growth hormone for idiopathic short stature in children and adolescents

Growth hormone injections appear to boost height in extremely short, healthy children, according to a recent systematic review, but height gain appears to peak at about three inches - and those inches are expensive.

Even after treatment, children with idiopathic — meaning their height does not result from a medical condition — short stature who received growth hormone injections remained relatively short, said Jackie Bryant, the review's lead author.

There is no indication that increases in height will improve a child's quality of life, the authors say.

Bryant, a senior research fellow at the University of Southampton in England, and colleagues analyzed 10 randomized controlled trials involving growth hormone therapy in 741 children with idiopathic short stature.

The studies compared children receiving growth hormone therapy for at least six months to children who did not receive treatment or who received a placebo.

Children with idiopathic short stature have heights well below the average for their age and sex, but are physically healthy and have normal laboratory results. If parents choose treatment, their children undergo years of recombinant human growth hormone injections, typically given six to seven times weekly at home.

Each half-inch in final height gained via human growth hormone therapy costs anywhere from $18,000 to $36,600.

The review appears in the latest issue of The Cochrane Library , a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

One of the studies took place in the United States and one in the United States and Chile; the remaining studies occurred in the United Kingdom, Australia, New Zealand, the Netherlands, Italy and Egypt. The current review, an update of a previous analysis, includes an additional trial conducted since 2003.

Generally, growth hormone injections increased height in these children, review results indicated.

In one study that followed children throughout adolescence, girls treated with growth hormone reached heights of about three inches taller than an untreated control group by near-adulthood. In another study, children treated with growth hormone were 1.4 inches taller than children treated with an inactive placebo.

In addition to gaining more inches overall, children treated with growth hormone also grew faster. In three studies, treated children experienced a significantly greater rate of growth after one year, compared to untreated children.

Despite these findings, children treated with growth hormone remained short — near the lower range of normal — when compared to their peers.

“Genetic factors affect growth and final height, and parents should be realistic in their expectations about the potential effects of growth hormone,” Bryant said.

In addition, despite its potential to increase height, growth hormone therapy can cause earlier onset of puberty, which paradoxically shortens the growth period and leads to premature closure of the ends of long bones, which may limit final height, Bryant said.

Steven Dowshen, M.D., a pediatric endocrinologist at Alfred I. duPont Hospital for Children in Wilmington, Del., praised the review's methods but said that much more research is necessary to evaluate the effectiveness of therapy in these kids.

“Many pediatric endocrinologists still do not consider the data and the potential benefits proven well enough to actually treat patients for this indication,” said Dowshen, who was not involved with the study.

“A lot of the reasoning behind treating this group of patients has traditionally been that they are socially or psychologically suffering because of their short stature or will later when they reach short final height as adults. … There's very scant evidence that the psychological, social and other outcomes are improved by therapy,” Dowshen said.

Only one study included in the review addressed psychological issues and found that children receiving growth hormone treatments reported no improvement in quality of life compared to children in the control group.

“These factors, plus the cost of treatment, which is substantial, make it unclear whether the small expected gain in height justifies such treatment in children who are not ill,” Bryant said.

Pharmaceutical companies sponsored or provided support for seven of the studies included in the review.

Bryant J, et al. Recombinant growth hormone for idiopathic short stature in children and adolescents. (Review). Cochrane Database of Systematic Reviews 2007, Issue 3.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.