Long-Term Safety of Growth Hormone Treatment in Childhood: Two Large Observational Studies: NordiNet IOS and ANSWER

Lars Sävendahl, Michel Polak, Philippe Backeljauw, Joanne C. Blair, Bradley S. Miller, Tilman R. Rohrer, Anita Hokken-Koelega, Alberto Pietropoli, Nicky Kelepouris, Judith Ross

Research output: Contribution to journalArticlepeer-review


Context: Growth hormone (GH) treatment has a generally good safety profile; however, concerns about increased mortality risk in adulthood have been raised. Objective: This work aims to assess the long-term safety of GH treatment in clinical practice. Methods: Data were collected from 676 clinics participating in 2 multicenter longitudinal observational studies: the NordiNet International Outcome Study (2006-2016, Europe) and ANSWER Program (2002-2016, USA). Pediatric patients treated with GH were classified into 3 risk groups based on diagnosis. Intervention consisted of daily GH treatment, and main outcome measures included incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to GH dose. Results: The combined studies comprised 37702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (eg, with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with more than one AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P=.003 and P=.001, respectively) and the non-SGA subgroup (both P=.002), and for SAEs in the intermediate-and high-risk groups (P=.002 and P=.05, respectively). Conclusions: We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group. A short visual summary of our work is available (1).

Original languageEnglish (US)
Pages (from-to)1728-1741
Number of pages14
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Jun 1 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.


  • SAGhE
  • adverse events
  • childhood
  • human growth hormone
  • long-term safety
  • neoplasms and malignancies

PubMed: MeSH publication types

  • Journal Article


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