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Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays
Published on: January 7, 2016
Long-term safety of recombinant human growth hormone in children
J Bell1, K L Parker, R D Swinford
1Columbia University Medical Center, New York, New York 10032, USA. jjb4@columbia.edu
Insights
Recombinant human growth hormone (rhGH) safety monitoring over 20 years shows leukemia risk is unconfirmed. However, NCGS data confirms risks of second malignancies in irradiated patients and highlights specific populations needing careful monitoring.
Area of Science:
- Endocrinology
- Pediatric Endocrinology
- Pharmacovigilance
Background:
- The National Cooperative Growth Study (NCGS) tracked the safety and efficacy of recombinant human growth hormone (rhGH) in 54,996 children from 1985 to 2006.
- This large-scale study aimed to identify potential adverse events associated with rhGH treatment in pediatric populations.
Purpose of the Study:
- To evaluate the long-term safety profile of recombinant human growth hormone (rhGH) in children.
- To investigate specific safety concerns, including leukemia, malignancies, diabetes mellitus, and other adverse events, associated with rhGH therapy.
- To identify specific patient populations at potential risk during rhGH treatment.
Main Methods:
- Longitudinal follow-up of 54,996 children treated with rhGH until discontinuation.
- Systematic collection and reporting of adverse events, with a focus on targeted or potentially rhGH-related events.
- Statistical analysis of observed versus expected event rates, including Standard Incidence Ratios (SIR) and 95% Confidence Intervals (CI).
Main Results:
- Concerns regarding de novo leukemia were not substantiated (SIR 0.54).
- No significant increase in de novo malignancies was observed in patients without risk factors (SIR 1.12).
- An increased risk of second malignancies was confirmed in patients with prior irradiation (49 cases), particularly those with retinoblastoma.
- Incidence of type 1 diabetes mellitus was comparable to expected rates (SIR 0.90); type 2 and unspecified DM were also reported.
- Specific risks were noted in certain conditions: deaths in Prader-Willi syndrome and aortic dissection in Turner syndrome.
- Acute adrenal insufficiency events, including fatalities, were observed in patients with hypopituitarism, consistent with known risks.
Conclusions:
- Long-term NCGS data confirms that leukemia is not a significant risk associated with rhGH therapy.
- The study identified and confirmed specific risks, notably second malignancies in previously irradiated patients.
- While rhGH demonstrates an overall favorable safety profile, these findings highlight the need for careful monitoring in specific pediatric subpopulations.
- The NCGS provides valuable insights into the long-term safety of rhGH, guiding clinical practice and risk management.
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.
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