Long-Term Safety of Recombinant Human Growth Hormone in Children
Long-Term Safety of Recombinant Human Growth Hormone in Children
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DOI：
10.1210/jc.2009-0178
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发表时间：
2010-01-01
影响因子：
5.8
通讯作者：
Lippe, B.
中科院分区：
文献类型：
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作者：
Bell, J.;Parker, K. L.;Lippe, B.
背景资料：在1985年和2006年之间，国家合作的生长研究（NCGS）监测的安全性和有效性的重组人生长激素（rhGH）在54,996 children.Methods：入组的患者进行了跟踪，直到rhGH停药。研究者提交了针对性事件或那些潜在的rhGH-related.Results的不良事件报告：早期关注的新发白血病患者没有危险因素尚未得到证实-三个观察与5.6预期年龄匹配的一般人群的基础上，在风险年[标准发病率比（SIR），0.54，95%置信区间（CI），0.11-1.58]。在无风险因素的患者中，原发恶性肿瘤（颅内和颅外）未显著增加（29例确认vs. 26例预期; SIR，1. 12; 95% CI，0. 75 - 1. 61）。49例患者发生第二种肿瘤，其中37例患者的初始肿瘤接受了放疗（包括16例视网膜母细胞瘤患者中的5例，其中3例患有双侧视网膜母细胞瘤），这与rhGH的风险增加一致。33例患者发生1型糖尿病（DM）（预期37例; SIR，0. 90; 95% CI，0. 62 - 1. 26）。分别有20例和8例患者报告了2型糖尿病和非特异性糖尿病。Prader-Willi综合征患者报告了2例死亡，Turner综合征患者报告了5例主动脉夹层死亡。在器质性GH缺乏症和特发性全垂体功能减退症患者中，发生了11起急性肾上腺功能不全事件，包括4例死亡，与报告的有或无rhGH治疗的肾上腺功能减退症患者肾上腺功能不全风险增加一致。20多年过去了，白血病，一个最初被认为与GH有关的主要安全问题，尚未得到证实，但其他信号，包括既往接受过放射治疗的患者发生第二次恶性肿瘤的风险，已通过NCGS检测或确认。这些数据进一步阐明了与rhGH相关的事件，尽管证实了有利的总体安全性特征，但也突出了存在潜在风险的特定人群。（临床内分泌代谢杂志95：167-177，2010）
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. (J Clin Endocrinol Metab 95: 167-177, 2010)