Long-Term Mortality after Recombinant Growth Hormone Treatment for Isolated Growth Hormone Deficiency or Childhood Short Stature: Preliminary Report of the French SAGhE Study

Department of Pediatric Endocrinology and Diabetology, Institut National de la Santé et de la Recherche Mdicale CIE5, Paris, France.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 02/2012; 97(2):416-25. DOI: 10.1210/jc.2011-1995
Source: PubMed

ABSTRACT Little is known about the long-term health of subjects treated with GH in childhood, and Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) is a study addressing this question.
The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France.
This was a population-based cohort study.
The setting of the study was a French population-based register.
A total of 6928 children with idiopathic isolated GH deficiency (n = 5162), neurosecretory dysfunction (n = 534), idiopathic short stature (n = 871), or born short for gestational age (n = 335) who started treatment between 1985 and 1996 participated in the study. Follow-up data on vital status were available in September 2009 for 94.7% of the patients.
All-cause and cause-specific mortality was measured in the study.
All-cause mortality was increased in treated subjects [standardized mortality ratio (SMR) 1.33, 95% confidence interval (CI) 1.08-1.64]. In a multivariate analysis adjusted for height, the use of GH doses greater than 50 μg/kg · d was associated with mortality rates using external and internal references (SMR 2.94, 95% CI 1.22-7.07, hazard ratio 2.79, 95% CI 1.14-6.82). All type cancer-related mortality was not increased. Bone tumor-related mortality was increased (SMR 5.00, 95% CI 1.01-14.63). An increase in mortality due to diseases of the circulatory system (SMR 3.07, 95% CI 1.40-5.83) or subarachnoid or intracerebral hemorrhage (SMR 6.66, 95% CI 1.79-17.05) was observed.
Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses. Specific effects were detected in terms of death due to bone tumors or cerebral hemorrhage but not for all cancers. These results highlight the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.

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    • "The recent publication of two studies stemming from SAGhE (Safety and Appropriateness of GH treatments in Europe) European consortium, which was started in 2009 and includes eight countries (France, Sweden, Belgium, the Netherlands, Switzerland, Germany, United Kingdom, and Italy), has generated confusion and controversy rather than shedding light on this delicate matter (Carel et al., 2012; Sävendahl et al., 2012). The French study reported a significant increase in both allcause mortality and specific mortality for bone tumors or cerebral hemorrhage in a cohort of about 6500 young adult subjects treated with rhGH during childhood for GH deficiency, SGA, or ISS (Table 1). "
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