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New research has linked growth hormone treatment to serious adverse health effects years later.
An 8-year-old boy I know is small for his age, shorter and slighter than his friends, even smaller than his 5-year-old sister. Concerned about the increasing use and possible risks of growth hormone, I asked his mother if she’d considered treating him with it. She replied, “Not really. He’s built like his father, who was short and slight as a boy and didn’t shoot up until college.”
Their son, she said, has no sign of a hormone deficiency. “He’s in the third percentile for height and has maintained the same growth trajectory for years, so there’s no reason to do something about it,” she said. “He’s very athletic, physically capable and can keep up with his friends in other ways.”
His father, at 41, is now 6 feet tall, though still very slender. He recalls being a reasonably athletic child but without the physical power of his friends, making up for what he lacked in mass with speed and agility. “I enjoyed competitive sports and worked on skills others didn’t have,” he told me, and said he encourages his son to recognize and capitalize on the skills he has.
If only every parent with a short but healthy child approached the matter as sensibly. Experts estimate that 60 percent to 80 percent of children who are short for their age do not have a growth hormone deficiency or other medical condition that limits growth. But knowing there’s a therapy available to increase height, some parents seek a medical solution for a perceived problem, even when there is no medical abnormality. They should also know, however, that new research has linked growth hormone treatment to serious adverse health effects years later.
Undue shortness may have many causes in addition to a deficiency of growth hormone, including malnutrition, Crohn’s disease or celiac disease, and potential medical conditions should be ruled out or, if present, treated. But height is most often related to the child’s genetics. Like father or mother, like son or daughter. Given the height of my parents — a 5-foot-1 mother and a 5-foot-6 father — I was not likely to become a forward for the Knicks at 4 feet 11.
Dr. Adda Grimberg, a pediatric endocrinologist at Children’s Hospital of Philadelphia, recalled that “20 years ago, families were focused on health. They came in with a child who was not growing right and wanted to know if there was an underlying disease. Now, more and more, they’re focused on height. They want growth hormone, looking for a specific height. But this is not like Amazon; you can’t just place an order and make a child the height you want.”
Originally, growth hormone was used to treat children with an established deficiency, which can result in a host of serious health problems. Cadavers were the initial limited source of the hormone until 1985, when scientists succeeded in producing recombinant human growth hormone in the laboratory, greatly increasing the supply and its use to treat growth hormone deficiency.
Estimates of the incidence of this deficiency range from one in 3,000 to one in 10,000 children. According to the Pediatric Endocrine Society, those affected are usually much shorter than their peers — well below the third percentile — and over time fall increasingly behind.
In 2003, the Food and Drug Administration approved use of recombinant human growth hormone for the condition known as “idiopathic short stature,” or short stature of unknown cause, which is not a disease. But it has prompted a growing number of parents to consider using the hormone to boost the height of their children. The resulting rush to therapy reflects concerns about a widespread societal bias against shortness, rather than a true medical need, Dr. Grimberg said.
Parents considering treatment for this otherwise medically benign condition should know what it entails: daily injections for years until the child’s growth is completed, rotating injection sites in the body to minimize scarring. Although few children experience side effects, which can include severe headaches and hip problems, treatment requires repeated doctor visits, X-rays and blood work and, Dr. Grimberg said, “gives the child a powerful message that there’s something wrong with him that needs fixing.”
According to the Pediatric Endocrine Society, the decision to administer growth hormone for idiopathic short stature should be made on a case-by-case basis in which benefits and risks are carefully considered for each child.
What, then, are the benefits and risks? Although manufacturers have supported monitoring drug safety beyond the 10 years mandated by the U.S. government, reporting is voluntary and necessarily incomplete. However, a far more reliable assessment is available from Sweden, where population-wide data are routinely collected.
In JAMA Pediatrics in December, pediatric endocrinologists from Karolinska University Hospital reported that among 3,408 patients who were treated with recombinant growth hormone as children and adolescents and followed for up to 25 years, the risk of developing a cardiovascular event like a heart attack or stroke was two-thirds higher for men and twice as high for women than among 50,036 untreated but otherwise similar people.
The Swedish finding follows a report last June from a research team in Tokyo that growth hormone promotes biomedical pathways that stimulate the development of atherosclerosis, the basis for most cardiovascular events.
Not yet known is whether other long-term adverse effects will become apparent in the years ahead. Based on its known action, giving growth hormone when no deficiency exists might raise the risk of cancer, respiratory disease and diabetes. In an editorial in JAMA Pediatrics, Dr. Grimberg wrote that “indirect evidence suggests that the potential for untoward effects of growth hormone treatment is sufficiently plausible” to warrant further study.
Equally important for parents to know is how much height their children might gain from years of daily hormone injections. Though impossible to predict in advance for an individual child, the average benefit for children with idiopathic short stature is about two inches in adult height. Dr. Grimberg suggested that if there is no measurable benefit within a year of therapy, parents should consider stopping it.
In discussing the psychological aspects of growth hormone therapy when no deficiency exists, experts have noted that the practice perpetuates the notion that short stature is unacceptable, leading to a spiraling demand for therapy. It is far better, one group suggested, to help a short child develop coping skills than to buy inches through pharmacological means.
In a report in Hormone Research in Pediatrics, Dr. Talia Hitt and colleagues at Children’s Hospital of Philadelphia and the University of Pennsylvania wrote that parents’ high expectations that growth hormone therapy will improve the quality of life for their children are unlikely to be met if the children are not hormone deficient. They urged clinicians to “support families in other ways that promote positive development in children with short stature.”
Dr. Philippa Gordon, a pediatrician in Brooklyn, N.Y., urges parents to make sure their children know “that people can be all different sizes and shapes and that their love for them is unconditional.”