Columbia University Medical Center, New York, New York 10032, USA.
J Clin Endocrinol Metab. 2010 Jan;95(1):167-77. doi: 10.1210/jc.2009-0178. Epub 2009 Nov 11.
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.
Enrolled patients were followed until rhGH discontinuation. Investigators submitted adverse event reports for targeted events or those potentially rhGH-related.
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.
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.
在 1985 年至 2006 年期间，国家合作生长研究（NCGS）监测了重组人生长激素（rhGH）在 54996 名儿童中的安全性和疗效。
入组患者随访至 rhGH 停药。研究者报告了针对目标事件或潜在与 rhGH 相关的不良事件。
最初人们担心无危险因素的患者新发白血病，但目前并未得到证实——根据发病风险年数，在年龄匹配的一般人群中，观察到 3 例，预期为 5.6 例[标化发病比（SIR），0.54；95%置信区间（CI），0.11-1.58]。无危险因素的患者新发恶性肿瘤（颅内和颅外）并未显著增加（确诊 29 例，预期 26 例；SIR，1.12；95%CI，0.75-1.61）。49 例患者发生第二肿瘤，其中 37 例因初始肿瘤接受放疗（包括 16 例视网膜母细胞瘤患者中的 5 例，其中 3 例为双侧视网膜母细胞瘤），这与 rhGH 相关的风险增加一致。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）。20 例患者报告发生 2 型 DM，8 例患者报告发生非特指型 DM。2 例死亡发生于 Prader-Willi 综合征患者，5 例死亡发生于 Turner 综合征患者。在有机 GH 缺乏症和特发性全垂体功能减退症患者中，11 例出现急性肾上腺功能不全，包括 4 例死亡，这与 GH 治疗的垂体功能减退症患者肾上腺功能不全风险增加的报告一致。
经过 20 多年，最初认为与 GH 相关的主要安全性问题白血病并未得到证实，但通过 NCGS，已检测到或证实了其他信号，包括放疗治疗过的患者新发恶性肿瘤的风险，以及其他特定人群的潜在风险。这些数据进一步阐明了与 rhGH 相关的事件，虽然证实了总体安全性良好，但也突出了特定人群的潜在风险。
