Correcting Short Stature: Long-Term Risks May Include Stroke

Early reports from the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) project noted increased cardiac and cerebrovascular mortality in adults who were treated for stature problems as children. In addition, other studies have linked stroke risk to short stature in general, hypothesizing that shorter people have increased metabolic risks.

Human growth hormone (GH or somatropin) is a mitogenic and proliferative agent. It is often used in children who are shorter than average to help them attain a more normal height. During informed consent, clinicians review a long list of possible acute side effects. Its long-term effects, however, are largely unknown, but researchers have been most concerned about possible cancer because of its cell-altering properties.

In the European Union, the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) project was established to monitor for late effects of GH treatment. Early reports from this project noted increased cardiac and cerebrovascular mortality in adults who were treated for stature problems as children. In addition, other studies have linked stroke risk to short stature in general, hypothesizing that shorter people have increased metabolic risks.

A study published in Neurology reports on the incidence of stroke and stroke subtypes in French patients treated with growth hormone (GH) for short stature in childhood. The researchers examined the study population—6,874 adults who were treated with GH between 1985 and 1996—between 2008 and 2010. They compared the incidence of stroke and of stroke subtypes to population-based values between 2000 and 2012.

Patients treated with GH in childhood had a significantly higher risk of stroke. Most of the excess risk of stroke was related to significantly higher risk of hemorrhagic stroke, especially subarachnoid hemorrhage. Long-term GH treatment may alter arterial structure and function.

Although the authors acknowledge that this study has certain limitations, the relationship between hemorrhagic stroke and GH treatment appeared to be strong. Significant debate has engulfed use of GH for short stature since its FDA approval. When GH is deemed necessary and appropriate, clinicians should counsel patients of short stature and their parents carefully about the risk of late effects. More research is needed to validate these findings and determine if this relationship is causal.