CoChat
Sign Up
Cited by 301Growth Hormone and Insulin-like Growth FactorsPituitary Gland Disorders and TreatmentsGenetic Syndromes and Imprinting

Long-term safety of recombinant human growth hormone in children

Bell, J., Parker, K. L., Swinford, R. D., Hoffman, A. R., Maneatis, T., Lippe, B.·2010·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2009-0178
Open this paper in CoChat — free account

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. CONCLUSION: 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.

Integrity signals

Registry

Crossref · 10.1210/jc.2009-0178

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Individuals with TS appear to be at increased risk of intracranial hypertension, slipped capital femoral epiphysis, and scoliosis during GH treatment compared with children with idiopathic GH deficiency or idiopathic short stature.

    “Individuals with TS appear to be at increased risk of intracranial hypertension and slipped capital femoral epiphysis208 as well as scoliosis173,198,208 during GH treatment compared with children with idiopathic GH deficiency or idiopathic short stature.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [208]

  • Data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.

    “data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.173,208,222-224”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [208]

  • 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 [208]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Bell, J., Parker, K. L., Swinford, R. D., Hoffman, A. R., Maneatis, T., & Lippe, B.
Affiliations
  • Columbia University Irving Medical Center (US)
  • The University of Texas Medical Branch at Galveston (US)
  • The University of Texas Health Science Center at Houston (US)
  • VA Palo Alto Health Care System (US)
  • Genentech (US)
Corresponding author
Bell, J.
ORCID
Hoffman, A. R.
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2010-01-01
Volume
95
Issue
1
Pages
167-177
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2009-0178
OpenAlex
W2150210382
Cited by
301
References
54
Citations by year
2026: 5 · 2025: 11 · 2024: 15 · 2023: 13 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 15 · 2015: 22 · 2014: 17 · 2013: 30 · 2012: 22
FWCI
15.03
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Genentech
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
recombinant human growth hormone, long-term safety, pediatric growth hormone therapy, de novo leukemia, secondary malignancies, radiation-induced cancer, retinoblastoma, type 1 diabetes, type 2 diabetes, Prader-Willi syndrome, Turner syndrome, aortic dissection, adrenal insufficiency, hypopituitarism
MeSH terms
Cause of Death, Child, Child, Preschool, Female, Follow-Up Studies, Growth Disorders, Humans, Male, Neoplasms, Pancreatitis, Product Surveillance, Postmarketing, Recombinant Proteins, Retrospective Studies, Scoliosis, Time Factors, Comorbidity, Incidence, Case-Control Studies, Human Growth Hormone, Diabetes Complications

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review