Does shortness need a cure?
Patricia Costa’s friends told her Nicole was a perfect little girl. Sure, she was tiny for a 3-year-old, but she was adorable and perfectly proportioned. She had a charming feistiness about her -- a determination that seemed to grow as Nicole confronted the childhood taunts of bigger peers and the indignities of being the smallest kid in school.
Like many other children who rank at the bottom of growth charts, Nicole had no identifiable disorder depressing her growth. So what if she’s tiny, Patricia’s friends insisted. The tests say she’s healthy. Why worry?
But Patricia saw a tiny girl on track to become a tiny woman -- 4 feet, 8 inches, by her doctors’ estimates -- and that prospect galvanized her to consider a course of costly and intrusive human growth hormone injections for her then 6-year-old daughter. “I’m thinking about when she’s 25 and walking into a courtroom with an attache case, or into a hospital with a stethoscope,” Patricia Costa said. “Being 4-foot-8 -- that just didn’t cut it.”
Today, Nicole is 18, and her first bid for power and influence has ended with success. After a seven-year course of human growth hormone injections, Nicole, now 5 feet, 2 inches, recently marched into a meeting room filled with federal regulators, physicians and medical ethicists and appealed to the Food and Drug Administration to sanction the use of human growth hormone by “all the children who now walk in the shoes I outgrew.”
In late July, the FDA did just that, expanding its approval of the synthetic human growth hormone -- Eli Lilly and Co.’s Humatrope -- to include children with “idiopathic short stature,” kids such as Nicole, whose shortness does not appear to be the result of underlying disease.
The decision could mean that as many as 400,000 U.S. children could get medication for a problem that lies in the ambiguous territory between personal obstacle, social prejudice and yet-to-be discovered medical disorder.
Like the FDA’s deliberations on drugs that treat complaints from shyness to depressed libido to acne, its latest decision takes the agency into some ethically tricky territory: Where do consumers’ often poignant demands and pharmaceutical companies’ desire to expand their markets fit into the process, next to safety and efficacy? And whose responsibility is it -- doctors’, patients’, insurance companies’ or the government’s -- to weigh whether a course of medical treatment, especially one that can bring only modest results, is worth the expense, the health risks and the attention of the medical community?
The FDA’s deliberations on Humatrope went beyond the traditional confines of technical reports about a drug’s safety and effectiveness. The FDA also reviewed various research that showed how short people are more likely to be bullied and teased in school, to consider themselves lonely, to have reduced marriage rates and to be perceived as having lower competence than people of ordinary height. Among these supportive studies were clinical comparisons showing increased self-esteem and decreased behavior problems among those whose height was enhanced with Humatrope’s use.
But Humatrope use had downsides as well. For some kids in the target group (children 7 to 15 years old), Humatrope does not work, and for many, even years of treatment will draw them just inside the range of “normal height.” A few children developed diabetes-like symptoms or curvature of the spine because of rapid growth. And researchers found 27 cases in which children taking Humatrope developed increased intracranial pressure that mimicked the symptoms of a brain tumor -- an apparent side effect that was reversible, but which required a painful and lengthy exam to rule out cancer.
The science of promoting growth has flourished since the late 1950s, when doctors first began administering a natural form of growth hormone derived from human cadavers to patients with growth deficits. In 1985, Lilly and several other drug firms began producing a synthetic form of human growth hormone, considered safer and easier to manufacture. Although thousands appear to have undertaken such treatment safely, its long-term effects remain uncertain, since many who took it as children are still in their 20s and 30s.
But other testimony considered by the FDA struck a decidedly more personal chord: There were painful accounts of playground taunting fests, of always being chosen last for a team, of being stuffed into lockers and garbage cans and dressed up like a baby. Nicole Costas recalled how lonely she felt waiting on the bench at an amusement park while friends went on rides she was too small for. How embarrassed she was when a kindergarten chair was brought in for her in second grade, because the teacher required all feet on the floor when children were at their desks. How thirsty she was because she couldn’t reach the water fountain.
Patricia Costa, now the executive director of the Human Growth Foundation, an advocacy group, sees the FDA’s decision on July 25 as evidence of “a system that works” to allow children to grow, literally, to their full potential. On the brink of the womanhood her mother imagined, Nicole Costa was just glad that she didn’t need to stand on a box to reach the FDA’s microphone.
For Lilly, the FDA decision is expected in the next five years to bring an additional 40,000 children and their families to the drug counter for treatment that costs $10,000 to $30,000 a year. The FDA’s decision will increase the pressure on health insurers, which have been reluctant to reimburse families for these treatments. Such treatments could reach $18 billion annually, according to one 1998 estimate.
While Lilly is a clear winner in the FDA decision, patients and doctors are likely to benefit as well, said Dr. Pinchas Cohen, a pediatric endocrinologist at UCLA. “This is going to make it easier for [pediatric endocrinologists] to practice the kind of medicine they think they should,” Cohen said. “People complain the insurance companies dictate how we can practice medicine: This decision will make it possible for us to do the right thing by our patients.”
But others view Humatrope’s approval as another disturbing move toward using medicine to treat societal ills that could be dealt with differently.
Steve and Lisa MacChesney’s 9-year-old daughter, Brittany, appears on course to fit the height profile for the FDA’s new decision. At school, Brittany’s 4-feet 1-inch frame has drawn taunts and bullying. But MacChesney, who owns several martial arts schools in the Orlando, Fla., area, and Lisa, a middle-school teacher, marched to Brittany’s school instead of a doctor’s office to solve the problem.
Steve MacChesney said he had used the same self-esteem and social skills he fosters in his schools to boost his daughter’s self-confidence, rather than focusing on her height. And he and his wife started a Web site dedicated to stamping out bullying. “I never thought about human growth hormone for her,” he said. “I always look at more natural responses before I go to the medicine side.... I’m a big proponent of self-esteem building.”
In a 1999 editorial in the New England Journal of Medicine, endocrinologist Sharon E. Oberfield called into question the use of growth hormone for the use of “idiopathic short stature,” noting that for many such children, years of treatments can yield very modest results. “Can we ... continue to practice medicine without responding to society, parents or our own biases?” asked Oberfield, of the Columbia University College of Physicians and Surgeons in New York. “I suggest we can practice and resist the pressure,” she added, “and that we should heed the advice of the Greek philosopher Epictetus, who stated that ‘reason is not measured by size of height but by principles.’ ”
Extreme short stature -- defined as 4 feet, 1 inches for a boy or girl age 10, or less than 4 feet, 11 inches for an adult woman or 5 feet, 3 inches for an adult man -- is not in itself a disease. But it is often the symptom of an underlying medical disorder, such as Turner’s syndrome, a genetic disorder that affects girls and women, chronic kidney failure or Prader-Willi syndrome, a development disorder that also is genetically based. In 1997, the FDA added “growth hormone deficiency” to the list of medical conditions that can cause extreme short stature, and for which the use of Humatrope was government approved.
UCLA’s Cohen says that in testing children for growth hormone deficiency, results range along a continuum. In defining a diagnosis for classical growth hormone deficiency, endocrinologists essentially chose an arbitrary number along that continuum. As a result, many small kids who could benefit from human growth hormone fell somewhere on the wrong side of the defined cutoff: They were out of luck, unless their doctor was willing to write an “off label” prescription for human growth hormone (legal, but largely nonreimbursable by insurance). Dr. David Orloff, director of the FDA’s division of metabolic and endocrine drug products, said the agency’s decision in no way brands unexplained “extreme short stature” a disease. Humatrope is used to treat the symptom of shortness in children with several recognized diseases, but even in those cases, it builds height rather than treating the underlying illness, he said. In approving the latest use for Humatrope, Orloff said, the FDA has gone no further.
Orloff said growth hormone was “by and large safe” in children and the side effects were mostly “reversible and monitorable.”
After the FDA’s move, Orloff said, “it’s up to parents and physicians to decide” whether it’s worth several years of nearly daily injections to increase a child’s full height by perhaps 2 to 3 inches over projections.
For Nicole Costa’s mom, that decision was made easier because her insurer paid for the treatments. But others anguish over the decision.
When Stephen Tucker of El Cajon, Calif., was 3, doctors diagnosed him with growth hormone deficiency and projected an adult height of less than 4 feet. Even then, his mother, Teresa, said she had doubts about proceeding with daily shots of a powerful hormone. And even at 3, Stephen had his own opinion of the treatment: He disliked the shots so much that his mother frequently had to fetch him from beneath a bed.
At age 13, however, after 10 years of human growth hormone treatment, he stood across from his mother’s 5-foot-1-inch frame and, for the first time, looked down on her. He was 5 feet, 2 inches, and he told his mother, “Mom, I’m taller than you. And if this is all the taller I ever get, it’s a darn sight better than 4 feet.” His mother cried.
“Society is so focused on stature that I didn’t want him to have to live his life wondering what if ... what if my mom and dad had given me the opportunity to grow normally?” said Tucker, whose son, now 18, is 5 feet, 7 inches tall. “I did not want to have to answer that question.”
