Until recently, little was known about the long-term effects of human growth hormone and endocrinologists felt confident there would be few long-term issues. Today, more experts fear the potential t risks of treatment—both physical and psychological. Is the worry warranted?
Before 2003, parents needed proof of a growth hormone deficiency or a related medical condition to get human growth hormone (HGH) treatments for their children.It was approved for growth hormone deficiency or very specific rare conditions qualified for treatment. Those conditions included chronic renal insufficiency, Prader-Willi syndrome, Turner syndrome, growth hormone or pituitary hormone deficiency or being small-for-gestational-age (underweight for the pregnancy week of birth).
In 2003, the FDA expanded the pool of children eligible to receive human growth hormone treatments by approving the new indication “idiopathic short stature,” which means that a child isn’t growing as expected, but doctors can’t find any clear cause for the stunted growth (such as malnutrition, liver disease or a neurological disorder). Now doctors can prescribe them to kids who are simply really, really short, even if it’s unclear why.
Since only one generation of children has had access to the treatment, more data exist to investigate side effects and outcomes. Still, the argument for using GH is inconclusive. In 2008, the Journal of Clinical Endocrinol Metabolism published research showing use of HGH in children without certain pre-condition had minimal results.
Starting human growth hormone treatments is not a decision doctors or families should take lightly. Reasons to be cautious include the cost, potential side effects and the psychological effects of giving your child a daily shot, which some experts say can make them feel as if there is something wrong with them.
“You have to be pretty dedicated to maximize the child’s height potential to go through the growth hormone pathway,” says Stephen Lauer, MD, PhD, an associate professor of pediatrics at The University of Kansas Medical Center in Kansas City. “You’re trying to convince an elementary school-aged child that it’s in their best interest to get a shot every day.”
Children undergoing growth hormone treatments receive 6 or 7 shots a week, every week, as long as they remain on the treatment. Most children receive treatment for 2 to 3 years, though some may stay on it for 5 to 10 years, according to Bradley S. Miller, MD, PhD, division director of pediatric endocrinology at the University of Minnesota in Minneapolis. How long they undergo treatment generally depends on when they start. “It can start from birth, and you can be treated until you’re done growing,” he says. Many children are referred to endocrinologists at around 11 years old, and the end of puberty generally marks the end of a person’s growth, about 17 for boys and age 15 for girls.
Pros and Cons
“As drugs go, it’s fairly safe,” says Paul Kaplowitz, MD, an endocrinologist affiliated with George Washington UniversityHospital in Washington, D.C., who literally wrote the book—The Short Child: a parents’ guide to the causes, consequences and treatment of growth problems. “We’re not introducing a foreign substance into the body. The synthetic form of growth hormone that is injected is identical to the growth hormone that is normally made by the pituitary glands.”
Still, he always explains to parents, “There’s no medical treatment that’s completely without risk.” Allergic reactions are extremely rare but possible. The most likely side effect is headaches. In about 5 percent of cases, a child can develop such extremely severe headaches that treatment is halted. In children with scoliosis, however, Dr. Miller says, growth hormone can worsen the condition. One small study also found that changes in children’s metabolism may lead to exceptional muscular forms. Inaccurate dosing can lead to overdoses, but a mathematical equation now offers calculations that make proper dosing less complicated, according to a 2007 study.
The bigger question, says Dr. Kaplowitz, is “What happens 20 years down the road?” Despite several European studies seeking to answer this question, long-term effects remain a mystery. Studies have not found evidence that growth hormone increases risk of stroke or death, but concerns over cancer risk are hazier; studies are inconclusive.
“Growth hormone doesn’t make cells become cancerous; it makes cancer cells that already exist grow faster,” explains Dr. Miller, pointing out that the studies do not show children developing new cancers if they’ve taken growth hormone. With that unknown out there, Dr. Kaplowitz reminds parents that treatment decisions are a matter of balancing potential benefits with some unknown risks.
How Short Is Too Short?
After the FDA’s 2003 approval, the expansion to idiopathic short stature opened up the treatment to children who were “short-normal,” Dr. Miller says. “They’re otherwise healthy but not growing like they should.”
To qualify, children’s height must be in the first percentile for their age with no expectation of catching up to any of the 99 percent of peers taller than them.
“There are lots of kids who are below the first percentile who are growing quite normally, and if you leave them alone, they’ll catch up just fine,” says Dr. Kaplowitz. In adults, the first percentile means 4 feet 11 inches for women or 5 feet 3 inches for men.
“Our tools to diagnose growth hormone deficiency aren’t perfect,” Dr. Miller says. “So there are some kids in the idiopathic group who probably don’t make enough human growth hormone.”
That’s likely what happened with Daniel Scarborough, a 13-year-old from Manteca, California, who began growth hormone treatments two years ago. As a micro preemie born at 24 weeks gestation — four months early — Daniel had always been tiny and he never caught up.
His borderline lab work did not definitively show him to be deficient in growth hormone. X-rays showed his hand bones to be 2 years younger than his chronological age, and a brain MRI revealed a grossly underdeveloped pituitary gland. These symptoms fell short of any diagnosis besides idiopathic short stature.
“It took a little more than 2 years of tests, frequent endocrinology visits, and a lot of discussions before we all could figure out a way to get coverage for HGH therapy,” Laura says. Her only regret was not starting sooner, but his earlier doctors disagreed on his need for it.
Keeping It Real
Nearly every doctor has encountered the parents who want their child eye-to-eye with Michael Jordan despite an unlikely family history, says Dr. Lauer. “The most basic thing to consider before treatments is parents’ expectations for their child’s height,” he says. “If the parents are 5 feet 6 inches and 5 feet 2 inches, and they have in the back of their mind that their kid will be 6 feet tall, that’s not going to happen. Part of it is just getting the parents to look at each other.”
In some very rare situations, though, a child might qualify if they’re above the first percentile but dramatically shorter than their genetics suggest they should be, according to Dr. Lauer. “If you have a super tall family and you should grow to 6 feet 2 inches, but you’re targeting 5 feet 6 inches because you’re not growing like you should for your family, you would meet the criteria for treatment because you’re so far below your own genetic curve,” Dr. Miller says.
Measuring the Benefits
But that kind of growth is unusual for most who receive treatment. Early studies found a gain of 2 to 3 inches with treatment, and more recent studies have suggested up to 4 or 5 inches, particularly for younger children, who tend to grow better, Dr. Miller says. In one study from 2015 researchers assessed the growth of 733 children with no diagnosis other than short stature. After 5 years of treatment, the children made up 60 percent of the difference between their original height and that of their average-height peers.
“It’s hard to predict in an individual case,” Dr. Kaplowitz says. “We’ve all seen patients we thought would improve with growth hormone and saw little improvement and other cases where improvement is significantly better than we expected.”
More typical is the experience of Alayna Dibo, a 26-year-old gymnast and social work graduate student from Chicago who took growth hormone from age 7 to age 16. With a 5-foot tall mom and a 5-feet-8-inch tall dad, her predicted height was 4 feet 7 inches before beginning treatment. Today, she’s exactly 5 feet and happy she spent those years getting 6 injections a week.
“I think about being 4 feet 7 inches tall in a professional environment and what that means,” she says. “I think I’m happier because it’s one less thing to worry about each day. Even at five feet, my height affects me. People think I’m younger than I am, and I’m not taken as seriously in the workplace.”
Psychological Impact Is Unclear
Although Dibo is grateful for her treatment, study data don’t show a clear increase in overall quality of life for children who receive treatment. A great deal of research in adults has linked short stature with a range of negative outcomes.
“The taller you are, the more likely you are to make more money, the more likely you’ll marry a taller person and be married at all and the lower your risk of suicide,” Dr. Miller says. But does receiving HGH treatment make a difference?
“We have no idea,” he says. “There are societal differences we’re aware of, but we don’t know if treatment actually helps that.”
Current studies are exploring how much being short affects children psychologically and whether treatment helps, but it’s a challenging question to answer.
“Does adding that inch or 2 improve their quality of life, their social functioning?” Dr. Kaplowitz says. “That’s a hugely controversial question because it’s harder to measure.”
Many children he has treated have been teased about their height, but most have developed strategies for dealing with it, and even with a couple extra inches, the child will be much shorter than his or her peers. “You can add an inch or two or, if you’re lucky, three,” Dr. Kaplowitz says. “It doesn’t necessarily mean they’re going to be a happier child or happier adult.”
Further, sending kids the message that being short is a medical problem may have its own harms, Dr. Miller says.
“For some people, it’s normal to be short,” he says. “[But] I do think that telling people that there’s something wrong with them because they’re short is a negative thing.”
Weighing The Pros and Cons
The more severe a height deficit, the more aggressively he believes they should be helping the child grow. “But if it doesn’t bother them and it’s not interfering with their lives, then there’s really no reason for us to intervene,” Dr. Miller adds.
When parents push for growth hormone but a child is less enthusiastic, the child’s self-esteem can take a hit, Dr. Kaplowitz says. “Unless the child is really short, I would try to convince the parents that their child is well-adjusted, they don’t want the treatment and the benefit is uncertain,” he says.
He also makes clear that most of the benefit for idiopathic short stature kids occurs in the first year: “After that, you don’t see continued extremely good growth in most cases.”
Practical concerns are the tipping point where doctors might advocate more for treatment, such as whether someone could fully participate in daily activities without significant effort.
“If I had a boy who would barely make it to 5 feet or a girl who might not make it to 4 feet 6 inches tall, I might try to convince the kid,” Dr. Kaplowitz says. “There’s a certain height where it’s inconvenient reaching things and driving cars.”
But buy-in from the child is key because the daily injections can take an emotional toll, particularly early on in treatment. Alayna Dibo’s mother, Carol, remembers having to chase Alayna around the house and then hold her down, screaming, to give her the injections.
“It was hard on me and hard on the other children, and I would cry at night,” Carol says. They returned to the endocrinologist and they got an Inject-Ease applicator that made the shots less painful. After that, the injections were just a normal part of her life. She even took them at camp with several other girls receiving daily growth hormone or insulin shots.
“A child who is very short and not growing very well and really wants growth hormone is less likely to complain about daily injections and visits than a child who is dragged into it unwillingly by their parents,” Dr. Kaplowitz points out.
Seeing fast results helped Daniel deal with the shots, too.
“It was a big adjustment for him as a child to deal with a daily injection,” says Laura. “He did understand, though, that his body needed the medicine to grow. We saw results fairly soon, and that encouraged him. Now it’s just a part of his nightly routine, no big deal.”
“There are plenty of well-adjusted short people out there, both kids and adults, who accept that they’re short and function at a very high level,” Dr. Kaplowitz says. “Having said that, there are individual patients who are extremely grateful and have benefited tremendously.”