Does GH therapy for idiopathic short stature put children at future risk?
Click Here to Manage Email Alerts
GH has a long-documented track record of safety, although potential benefits and risks should always be discussed.
When talking about treating children with unequivocal growth hormone deficiency, who in the absence of GH therapy have little chance of achieving normal adult stature, the overwhelming majority of endocrinologists would say yes, even though GH has some documented risks and may have some potential theoretical risks. With a condition like idiopathic short statue, the benefit of GH therapy, in general, is not as obvious as with GH deficiency. That forces one to possibly reassess the risk vs. benefits.
I would still argue that GH has an outstanding and long-documented track record of safety. Concerns that have been raised in the past decade about cancer risk, cardiovascular risk and cerebrovascular risk have not been well corroborated and do not change the paradigm I use for whether to recommend therapy. Risk for increased mortality originally described in a French study in 2014 has not been replicated by other groups. That does not de-legitimize the French findings, but it does put it in perspective; that is why we have peer-reviewed papers.
There are a number of potential benefits with GH therapy in idiopathic short statue. The most obvious is improvement of adult height, in some cases reaching genetic target height or even exceeding target height. We should also remember that these are children. By the time they come to an endocrinologist’s attention, they typically are already quite small relative to their peers. This often means parents have held them back in school; it often means friends and relatives have tended to infantilize them. Helping short children catch up with their peers is an independent benefit beyond adult height.
In general, most studies indicate that improvement in adult statue in idiopathic short statue is not as great as in GH deficiency, but there is tremendous variability. Some with idiopathic short statue grow as if they had GH deficiency. Others grow more modestly. Still others see little to no improvement in growth velocity.
We are now entering an era where long-acting GH preparations will become available soon. That provides us all with an opportunity for reassessing any potential risks. I have every hope that we will be careful and there will be extensive monitoring of any short-term and long-term effects with GH therapy.
Ron G. Rosenfeld, MD, is emeritus professor and chair of the department of pediatrics at Oregon Health & Science University.
The long-term effects of pediatric GH therapy are not known.
The safety issue surrounding GH therapy in the short term is virtually certain. However, long-standing concerns exist regarding a potential association between GH treatment and the development or recurrence of neoplasms and the effect on glucose homeostasis, including development of type 2 diabetes. More recently, data from the French cohort of the European Union’s SAGhE study raised concerns for premature mortality and intracranial hemorrhage among young adults treated with GH during childhood.
Results from the observational GENESIS study indicate that the benefit-risk profile of GH remains favorable, although average follow-up time within the study was relatively short.
GH therapy was once one of the safest drugs we prescribed. We saw no side effects. In the 1980s, we discovered Creutzfeldt-Jakob disease with pituitary-derived GH. Today, the SAGhE data show short-term safety; however, it begs the question of long-term safety. The proper study with long-term follow-up simply cannot be done.
If I have a patient with a diagnosis of idiopathic short statue, we discuss that GH therapy might be helpful. However, if we try GH — which would be an n = 1 experiment — and that individual does not grow 2.5 cm more than previously during the first year, then it is futile therapy. We do not marry the patient to this drug for 7 or 9 years and see what happens. With idiopathic short statue, that is a rational way to go about it. The biggest side effect of GH therapy is unmet growth expectations. For GH deficiency, the choice is easy. Idiopathic short statue is different.
Many pharmaceutical companies produce GH. Those databases could be combined but have not been. Additionally, several long-acting GH formulations are now in the pipeline; each is a different chemical entity. If we are ever going to find out about issues like risk for stroke, my plea would be long-term follow-up of these patients. These are different compounds, and there may very well be different side effects.
Alan D. Rogol, MD, PhD, is emeritus professor of pediatrics at the University of Virginia.
- References:
- Child CJ, et al. J Clin Endocrinol Metab. 2019;doi:10.1210/jc.2018-01189.
- Sävendahl L, et al. Lancet Diabetes Endocrinol. 2020;doi:10.1016/S2213-8587(20)30163-7.
Collapse
Click Here to Manage Email Alerts