Growth Hormone Use in Kids Greatly Increases The Chance For A Stoke When They Are Young Adults

Growth Hormone Use in Kids Linked to Stroke in Young Adults

Growth hormone use in kids for the treatment of short stature or growth hormone deficiency in childhood increases the long-term the risk for stroke in young adulthood, hemorrhagic strokes in particular, French registry data show.growth hormone use in kids

Investigators at the University of Lorraine in France found that growth hormone use in kids resulted in a SIGNIFICANTLY HIGHER risk for stroke among patients treated with growth hormone in childhood compared with 2 population-based registries used as reference controls.

The excess risk for stroke was mainly attributable to a “very substantially and significantly higher risk” of hemorrhagic stroke, at a standardized incidence ratio (SIR) ranging from 3.5 to 7.0 (the higher the number the more incidence of stroke), depending on the registry rates considered.

The study was published online August 13 in Neurology.

Detailed Growth Hormone in Kids Study

“In 2012, we analyzed the same French cohort of growth hormone use in kids treated for short stature or idiopathic growth hormone deficiency which revealed larger numbers of death from cerebral vascular accidents (CVAs), including brain and meningeal hemorrhages in particular in treated individuals,” lead investigator, Joël Coste, MD, PhD, head of the biostatistics and epidemiology unit at Hotel Dieu, University of Paris, France.

“This finding justified a more detailed study, focusing in particular on the frequency of non-lethal CVAs in this population. And we observed a significant increase in CVA risk, with treated individuals 1.5 to 5.3 times more likely to experience a CVA than individuals from the general population!

The earlier study was published in the Journal of Clinical Endocrinology and Metabolism (2012;97:416-25).

For both studies, investigators mined the French study the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) for cerebrovascular morbidity data in a population-based cohort of patients treated with growth hormone.

They specifically studied the incidence of stroke and all stroke subtypes, including subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke, in this cohort.

Investigators limited the analysis to children who were treated for idiopathic isolated growth hormone deficiency, idiopathic short stature, short stature in children born short for gestational age, or isolated growth hormone deficiency associated with a minor craniofacial malformation.

In total, 6874 children were included in this group. Most children in the group were treated for isolated growth hormone deficiency.

A total of 18 events were identified in this previously low-risk group of children, 11 of which were finally validated as incident cases of stroke by hospital reports and imaging results.

Specifically, there were 5 subarachnoid hemorrhages, 3 intracerebral hemorrhages, and 3 ischemic strokes.

The mean age at the time of stroke was 24.2 years, and 4 patients died, including 3 who had a subarachnoid hemorrhage.

Risk/Benefit Assessment of Growth Hormone Use in Kids

Investigators then used a special statistical method, the “capture-recapture” model, to account for patients for whom it was not possible to obtain information about possible nonfatal CVAs.

Using this model, “…total number of incident strokes was 16.3,” investigators report — 11 cases detected at an estimated 5.3 cases missed.

Similarly, the number of intracerebral hemorrhages was 4.9, yielding a total of 12.9 incident hemorrhagic strokes in the growth hormone cohort.

The authors found an increased incidence of stroke relative to the 2 population-based registries, with an SIR of 2.2 to 5.3 for all stroke subtypes and an SIR of 5.7 to a 7.0 for hemorrhagic stroke.

Table: SIR’s for Different Stroke Subtypes

Dijon Registry

Stroke Subtype

SIR

Hemorrhagic Stroke

3.5

Subarachnoid Hemorrhage

5.7

Intracerebral Hemorrhage

2.1

Ischemic Stroke

 0.6

Oxford Registry

Stroke Subtype

SIR

Hemorrhagic Stroke

4.4

Subarachnoid Hemorrhage

6.3

Intracerebral Hemorrhage

2.9

Ischemic Stroke

2.4

“…in the case where growth hormone is being used merely for the treatment of short stature, the benefits of gaining a few centimetres in growth should be assessed against the risk.”

“Much Anticipated” Growth Hormone Use in Kids Report

In an accompanying editorial, extract Rebecca Ichord, MD, University of Pennsylvania, Philadelphia, noted that this report has been “much anticipated” by the endocrinology community because it extends and clarifies findings in the 2012 SAGhE study, which showed an increase in deaths in adults treated in childhood with growth hormone.

“Major strengths [of the current study] include the large sample size arising from a mandatory large national treatment registry and the long duration of follow-up,” Dr. Ichord observed.

“…the implications for clinical practice are potentially urgent and immediate,” Dr. Ichord writes. Based on the available data, practitioners who prescribe growth hormone should consider the potential risk for long-term stroke in their counseling about risks and weigh this risk in their own recommendations when determining “net benefit” to the patient.

It may also be prudent to counsel these patients about the importance of primary prevention strategies for cerebrovascular risk factors throughout adult life, she adds.

“The concept of negligible risk is a standard by which treatments given to healthy children at very high cost should be judged,” she concludes. “Even a very small increase in risk of a condition with fatal or severely disabling consequences violates this standard.”

The study was funded by the French drug safety agency (AFSSAPS), the French Ministry of Health, the Institut National du Cancer and a Commission of European Communities Grant

Neurology. Published online August 13, 2014. Abstract Editorial

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