Controversy surrounds growth hormone use

Although growth hormone was approved for the treatment of ISS in 2003, doctors are divided about its use.

Issue: April 2006

Following expanded indications approved by the FDA, demand for growth hormone has increased. Controversy regarding its use, however, has escalated as a result.

In 2003, the FDA approved growth hormone as a treatment for pediatric patients with idiopathic short stature (ISS). This significantly increased the number of patients eligible to receive growth hormone treatment and set off a storm of controversy regarding optimal and appropriate medical interventions for short stature.

The new FDA guidelines stipulated that growth hormone can be considered an appropriate treatment for pediatric patients with ISS whose height is more than 2.25 standard deviations below the mean and who are considered unlikely to reach normal adult height.

Who to treat

Prior to its approval as a treatment for ISS, growth hormone was used as a treatment for several conditions, including growth hormone deficiency, chronic renal failure and Turner’s syndrome.

With the expanded indication to include ISS, physicians are now treating an increasing number of pediatric patients with growth hormone, but the medical community remains somewhat divided about this practice.

Supporters of the expanded indication for growth hormone say the treatment will help children who are short to achieve average height and may help them have a more normal life. But it is difficult to prove the necessity of the treatment. Children who are short may be suffering because of their height, but it is nearly impossible to determine to what extent.

Physicians face difficult decisions when deciding which patients to treat. “A lot depends on the psychosocial issues of the patients,” Janet Silverstein, MD, from the department of pediatrics in the division of endocrinology at the University of Florida in Gainesville, told Endocrine Today.

“Doctors need to examine how height is affecting their patients’ lives. Patients whose height is interfering with their lives may need to be treated. But some short children who come from short families do not necessarily need growth hormone treatment, unless their height is interfering with functioning.”

Selma Witchel, MD, from the department of pediatric endocrinology at the Children’s Hospital of Pittsburgh, told Endocrine Today that different pediatric endocrinologists likely use differing criteria to determine which patients might benefit from growth hormone therapy.

“You might get dissimilar answers from a group of pediatric endocrinologists,” she said. “Personally, I look at absolute height and growth velocity. I would consider treatment if the patient has short stature [height SDS is more than 2.5 below the mean], subnormal growth velocity and the projected adult height is much lower than the predicted target height based on mid-parental height.” Witchel also mentioned that it is important to gauge the patient’s and the parent’s level of concern because some patients are more troubled by their height than others.

David Allen, MD, from the University of Wisconsin in Madison, said doctors should try to determine how responsive a patient will be and assess how much height might be gained. “It is important to determine which patients are most in need of growth hormone treatment, as measured by the severity of the height disparity,” Allen said. “We should target children who are truly disabled by their height and who will succeed with this treatment.”

Treatment regimen

Once a patient is approved to receive growth hormone therapy, the treatment regimen is extensive. Patients are required to inject shots of growth hormone five to seven times per week. This usually continues for five to six years. Annual treatment costs can range from $10,000 to $20,000 or more.

The results of the treatment can vary. Studies have shown that the average patient achieves two to three inches in final height gain at the end of therapy. Some patients gain less height, however, and some do not respond to the treatment at all.

Because of the intensity of growth hormone treatment, dropout rates are high. Pediatric patients often find the daily injections too difficult or become frustrated with what they think are poor results. Some physicians estimate that as many as 40% of patients who begin a growth hormone treatment regimen do not follow it through to completion.

Since the treatment may not achieve results for some patients, physicians must monitor patients to determine whether continuing the regimen is practical. “Doctors should pay close attention, particularly during the patient’s first six months of treatment,” Silverstein said. “If the treatment is not working, I recommend discontinuing treatment immediately.”

Ethical concerns

Ethical concerns regarding growth hormone treatment are widespread among health care professionals and the general population.

Arthur Caplan, PhD, chair of the department of medical ethics and director of the Center for Bioethics at the University of Pennsylvania in Philadelphia, said some doctors have ethical concerns regarding growth hormone as a treatment for ISS because there are questions regarding the medical necessity of such therapy.

“The problem with the expanded indication for growth hormone is that it starts to creep into aesthetic issues,” Caplan told Endocrine Today. “We have to determine where to draw the line.”

Caplan also said he has ethical concerns because most of the patients being treated with growth hormone begin the regimen as fairly young children. “The patients are usually too young to give competent consent,” he said. “Furthermore, it is a burdensome treatment with relatively low efficacy.”

Many doctors are hesitant because of the burdens associated with growth hormone treatment. “It is painful and intrudes on a child’s lifestyle,” Caplan said. “It also stigmatizes the child. They become a short child who needs shots to correct this problem. If the patient didn’t think height was an issue before, it will become an issue once treatment is underway.”

Use of resources

As the costs associated with growth hormone treatment rise, doctors are increasingly concerned if this is the best use of health care resources. For many doctors, it is hard to justify the economic costs, especially since many insurance companies do not cover growth hormone treatment and the patients’ well-being and quality of life is difficult to measure.

Allen said the economic burden is a major concern for many doctors. “I question in many cases if this is an appropriate allocation of resources,” Allen said. “Growth hormone remains expensive, particularly in later years of treatment, and the question remains: How much should you spend trying to achieve a height that is greater than others already in the normal range? It is difficult to justify in ethical grounds.”

The financial burden will prevent some patients from getting the treatment, even though they meet the criteria. “If the medical profession has used growth hormone to gain a perceived advantage for some by making them taller, this becomes unfair to those now shorter individuals who did not have the opportunity to receive treatment,” he said.

The FDA decision

Despite the controversy, many doctors believe the FDA made the right decision when expanding the indication of growth hormone treatment. Mark Sperling, MD, also from the department of pediatric endocrinology at the Children’s Hospital of Pittsburgh, said he believes the FDA panelists acted appropriately when deciding to expand the indication to include pediatric patients with ISS.

“When the data were reviewed, it was the opinion of the panelists that these children would benefit from growth hormone treatment. The panelists acted correctly on the basis of the information presented to them,” Sperling told Endocrine Today.

Sperling added that he has concerns about the future of growth hormone treatment. “If we are now supposed to treat everyone who is going to be short, we will increase the average height of the general population,” he said. “Then 5’5” is going to be the new ‘short.’ Are we then going to have to treat patients at that height? When does it stop?” – by Jay Lewis