title: Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France.
  
  
  METHODS
  This was a population-based cohort study.
  
  
  METHODS
  The setting of the study was a French population-based register.
  
  
  METHODS
  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.
  
  
  METHODS
  All-cause and cause-specific mortality was measured in the study.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Institut National de la Santé et de la Recherche Mdicale CIE5, Paris, France. jean-claude.carel@inserm.fr
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ecosse
authors.forename: Fabienne
authors.initials: F
authors.lastname: Landier
authors.forename: Djamila
authors.initials: D
authors.lastname: Meguellati-Hakkas
authors.forename: Florentia
authors.initials: F
authors.lastname: Kaguelidou
authors.forename: Grégoire
authors.initials: G
authors.lastname: Rey
authors.forename: Joël
authors.initials: J
authors.lastname: Coste
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006130:Growth Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D013006:Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011153:Population; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013006:Growth Hormone