title: Long-term safety of recombinant human growth hormone in children.
abstract: BACKGROUND
  Between 1985 and 2006, the National Cooperative Growth Study (NCGS) monitored the safety and efficacy of recombinant human growth hormone (rhGH) in 54,996 children.
  
  
  METHODS
  Enrolled patients were followed until rhGH discontinuation. Investigators submitted adverse event reports for targeted events or those potentially rhGH-related.
  
  
  RESULTS
  Early concerns about de novo leukemia in patients without risk factors have not been substantiated--three observed vs. 5.6 expected in age-matched general population based on years at risk [standard incidence ratio (SIR), 0.54; 95% confidence interval (CI), 0.11-1.58]. De novo malignancies (intracranial and extracranial) were not significantly increased in patients without risk factors (29 confirmed vs. 26 expected; SIR, 1.12; 95% CI, 0.75-1.61). Second neoplasms occurred in 49 patients, of whom 37 had irradiation for their initial tumors (including five of 16 retinoblastoma patients, three of whom had bilateral retinoblastoma) consistent with an increased risk with rhGH. Thirty-three patients developed type 1 diabetes mellitus (DM) (37 expected; SIR, 0.90; 95% CI, 0.62-1.26). Type 2 DM and nonspecified DM were reported in 20 and eight patients, respectively. Two deaths were reported in patients with Prader-Willi syndrome and five deaths from aortic dissection in patients with Turner syndrome. In patients with organic GH deficiency and idiopathic panhypopituitarism, 11 events of acute adrenal insufficiency occurred, including four deaths, consistent with a reported increased risk for adrenal insufficiency in hypopituitary patients with or without rhGH treatment.
  
  
  CONCLUSIONS
  After more than 20 yr, leukemia, a major safety issue initially believed associated with GH, has not been confirmed, but other signals, including risk of second malignancies in patients previously treated with irradiation, have been detected or confirmed through the NCGS. These data further clarify the events associated with rhGH and, although confirming a favorable overall safety profile, they also highlight specific populations at potential risk.
authors.affiliation: Columbia University Medical Center, New York, New York 10032, USA. jjb4@columbia.edu
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: K L
authors.initials: KL
authors.lastname: Parker
authors.forename: R D
authors.initials: RD
authors.lastname: Swinford
authors.forename: A R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: T
authors.initials: T
authors.lastname: Maneatis
authors.forename: B
authors.initials: B
authors.lastname: Lippe
mesh_terms: D016022:Case-Control Studies; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D048909:Diabetes Complications / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D019382:Human Growth Hormone / Q000009:adverse effects* / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D010195:Pancreatitis / Q000139:chemically induced / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012600:Scoliosis / Q000139:chemically induced / Q000453:epidemiology; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone