Eric Gopel, MD, on Growth Hormone Therapy in Patients With IGF1R Mutation – MedPage Today

Posted: March 21, 2020 at 12:55 am

While patients who are born small for their gestational age (SGA) have shown improvement with recombinant human growth hormone (rhGH) therapy, not much research has been conducted on patients who have the IGF1R mutation.

That's why Eric Gpel, MD, and colleagues conducted a study of these patients, which has been published in the Journal of Clinical Endocrinology & Metabolism. They found that while IGF1R carriers did show a lower growth response, they did catch up with other SGA patients.

Dr. Gpel answered some of MedPage Today's questions about their research on hormone therapy for these patients.

Why did you decide to study growth hormone (GH) therapy response in IGF1R patients?

Gpel: Although IGF1R mutations were first described in SGA patients more than 15 years ago, studies examining patient characteristics and treatment options in a cohort are very rare. Most probably IGF1R patients have been treated with the diagnosis "small for gestational age without catch-up growth" for a long time, without knowing the molecular diagnosis, and while case descriptions provided first hints on therapeutic success, cohort analyses were lacking.

You found that IGF1R mutation carriers showed a more pronounced growth retardation and lower response to rhGH therapy than others and that IGF1R mutation good responders showed catch-up growth to the levels of SGA patients. Were these results surprising to you?

Gpel: The clinical experience of our pediatric endocrinologists and various case reports gave the impression of a poorer therapeutic outcome compared to SGA patients. In addition, a lower response to GH could be expected due to the fact that the (aberrant) IGF1 receptor is at the lower end of the growth hormone axis. However, we were surprised by the high variability among patients; the more as we could not find any significant correlation with the kind of mutation. However, growth is a multifactorial process and other, genetic or non-genetic factors, can be expected to modify the response to GH.

What would you say to a physician who finds these results discouraging when it comes to treating patients with the IGF1R mutation?

Gpel: The decision in favor of a GH therapy should, of course, not be taken lightly. However, our study showed that -- despite a somewhat poorer average response -- some patients in the group of IGF1R mutation carriers clearly can benefit from GH therapy. Currently, it is simply not predictable how well or poorly a specific patient will respond to GH therapy. For this reason, we recommend favoring a treatment, re-evaluating the success of therapy periodically, and considering discontinuation of treatment in case of a poor response.

What would you like to see happen as a result of your study? More research? Clinical practice changes?

Gpel: IGF1R deficiency is a relatively rare finding and our study cohort is comparably small. Therefore, further studies are needed to identify factors that make GH treatment success in individual patients more predictable. This will make therapy decisions easier for pediatricians and parents. A distant aim would be to provide an estimation of therapy success according to the patients' individual mutation based on large cohort studies.

You concluded that IGF1R mutation should not be excluded from rhGH treatment, but that a critical re-evaluation of success should be performed periodically. How often do you recommend re-evaluation? What are some key things clinicians should be looking for when they re-evaluate?

Gpel: We would suggest regular control intervals of about half a year with special attention to changes of growth rate. The increment of height velocity SDS values within the first year of treatment could provide initial information about responsiveness. Of course, other aspects such as therapy adherence, socio-psychological aspects, and potential side effects have to be taken into account since GH therapy is a long-lasting treatment.

Is there anything else physicians should know about IGF-1 serum levels?

Gpel: We think that therapy monitoring by IGF-1 serum levels is one of the most difficult aspects in the treatment of SGA patients with IGF1R defects. They tend to have elevated IGF-1 levels, especially under treatment with GH. Because we do not have long-time outcome data, it is difficult to advise which is the upper acceptable limit in a patient with IGF-1 resistance under GH treatment that is both safe and that provides the best therapeutic outcome. Therefore, we recommend following these patients closely and collecting data carefully.

You can read expert commentary about the clinical implications of this study here and review the abstract here.

Last Updated March 17, 2020

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Eric Gopel, MD, on Growth Hormone Therapy in Patients With IGF1R Mutation - MedPage Today

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