Weighing the Use of Growth Hormones for Children
JANE E. BRODY
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.”
费城儿童医院(Children s Hospital of Philadelphia)的儿童内分泌学家阿达·格里姆伯格(Adda Grimberg)博士回忆道，“20年前，家庭关注的是健康。家长带着个头不对的孩子来医院，想知道的是他们是否有潜在疾病。现在，家长越来越关注身高。他们想要生长激素，长出特定的身高。但这不是亚马逊(Amazon)；你不能靠下个单就把孩子的身高变成你想要的样子。”
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.
据估计，这一缺乏症的儿童发病率在3000分之一到10000分之一不等。根据儿科内分泌学会(Pediatric Endocrine Society)的数据，受此影响的人通常比同龄人矮得多（远低于第三百分位），且随着时间推移，他们的身高数据会越来越落后。
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.
2003年，美国食品与药品管理局(Food and Drug Administration)批准将重组生长激素用于所谓的“特发性矮小”，或不明原因矮小的问题，但这并不是疾病。这也促使越来越多的父母考虑使用该激素让孩子长高。格里姆伯格表示，由此产生的治疗热潮反映了对普遍存在的矮个偏见的担忧，而非真正的医疗需求。
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.
在《美国医学会杂志·儿科》(JAMA Pediatrics)的12月刊中，卡罗林斯卡大学医院(Karolinska University Hospital)的儿科内分泌学家报告称，儿童和青少年时期进行重组生长激素治疗、并接受最长达25年随访的3408名患者，与未接受治疗但其他状况类似的50036名患者相比，男性发生诸如心脏病发作或中风等心血管事件的风险高出三分之二，女性则高出两倍。
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.”
费城儿童医院的塔莉亚·希特(Talia Hitt)博士及其同事联合宾夕法尼亚大学在《儿科激素研究》(Hormone Research in Pediatrics)期刊发表的一份报告中写道，如果孩子没有激素缺乏，家长对生长激素疗法改善孩子生活质量的过高期待不太可能得到满足。他们敦促临床医师用其他方式来“支持家庭，以促进矮小儿童的积极发展”。
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.”