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Cited by 80Growth Hormone and Insulin-like Growth FactorsPituitary Gland Disorders and TreatmentsGenetic Syndromes and Imprinting

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

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Child, Christopher J, Zimmermann, Alan G, Chrousos, George P, Cummings, Elisabeth, Deal, Cheri L, Hasegawa, Tomonobu, Jia, Nan, Lawrence, Sarah +11 more·2019·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2018-01189PMC PMC6300411
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Abstract

Context: Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. Objective: To assess incidence of key safety outcomes. Design: Prospective, multinational, observational study (1999 to 2015). Setting: A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Patients: Children with growth disorders. Interventions: GH treatment. Main outcome measures: Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Results: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. Conclusions: GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors.

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  • No overall increase in mortality due to GH relative to other GH-treated pediatric populations has been reported in TS individuals in GH registries.

    “No overall increase in mortality due to GH relative to other GH-treated pediatric populations has been reported in individuals with TS followed in the GH registries.173,197,208,225”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [225]

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Authors
Child, C. J., Zimmermann, A. G., Chrousos, G. P., Cummings, E., Deal, C. L., Hasegawa, T., Jia, N., Lawrence, S., Linglart, A., Loche, S., Maghnie, M., Pérez Sánchez, J., Polak, M., Predieri, B., Richter-Unruh, A., Rosenfeld, R. G., Yeste, D., Yorifuji, T., & Blum, W. F.
Affiliations
  • Eli Lilly (United Kingdom) (GB)
  • Eli Lilly (United States) (US)
  • National and Kapodistrian University of Athens (GR)
  • Dalhousie University/IWK Health Centre, Halifax, Nova Scotia, Canada
  • Centre Hospitalier Universitaire Sainte-Justine (CA)
  • Keio University (JP)
  • Children's Hospital of Eastern Ontario (CA)
  • Hôpital Bicêtre Paris Sud, Paris, France
  • Ospedale Microcitemico (IT)
  • Istituto Giannina Gaslini (IT)
  • Corporació Sanitària Parc Taulí, Sabadell, Spain
  • Hôpital Necker-Enfants Malades (FR)
  • University of Modena and Reggio Emilia (IT)
  • University Hospitals of the Ruhr-University of Bochum (DE)
  • Oregon Health & Science University (US)
  • Universitat Autònoma de Barcelona (ES)
  • Osaka City General Hospital (JP)
  • Justus-Liebig-Universität Gießen (DE)
Corresponding author
Child, Christopher J
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2018-09-13
Volume
104
Issue
2
Pages
379-389
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2018-01189
PMC
PMC6300411
OpenAlex
W2891605529
Cited by
80
References
47
Citations by year
2026: 5 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 16 · 2021: 11 · 2020: 9 · 2019: 6 · 2017: 1
FWCI
5.17
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
Funders
  • Eli Lilly and Company
  • Pfizer
  • Merck KGaA
  • Novo Nordisk
  • EMD Serono
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
pediatric growth hormone therapy, treatment safety, mortality, type 2 diabetes, primary tumor, second neoplasms, hemorrhagic stroke, growth disorders, short stature, growth hormone deficiency, idiopathic short stature, Turner syndrome, Genesis, standardized mortality ratio, standardized incidence ratio, cancer survivors, risk factors, pediatric endocrinology
MeSH terms
Adolescent, Cerebral Hemorrhage, Child, Child, Preschool, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Growth Disorders, Humans, Male, Neoplasms, Prospective Studies, Recombinant Proteins, Risk Factors, Incidence, Human Growth Hormone

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