title: Overall and cause-specific mortality in GH-deficient adults on GH replacement.
abstract: OBJECTIVE
  Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients.
  
  
  METHODS
  In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available.
  
  
  METHODS
  This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05.
  
  
  RESULTS
  All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044).
  
  
  CONCLUSIONS
  GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.
authors.affiliation: Department of Endocrinology, Diabetology and Metabolism, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Anders F
authors.initials: AF
authors.lastname: Mattsson
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Akerblad
authors.forename: Bengt-Åke
authors.initials: BÅ
authors.lastname: Bengtsson
authors.forename: José
authors.initials: J
authors.lastname: Cara
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
authors.forename: Maria
authors.initials: M
authors.lastname: Koltowska-Häggström
authors.forename: John P
authors.initials: JP
authors.lastname: Monson
authors.forename: Bernhard
authors.initials: B
authors.lastname: Saller
authors.forename: Patrick
authors.initials: P
authors.lastname: Wilton
authors.forename: Roger
authors.initials: R
authors.lastname: Abs
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects* / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016012:Poisson Distribution
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I