Mills James L, Schonberger Lawrence B, Wysowski Diane K, Brown Paul, Durako Stephen J, Cox Christopher, Kong Fanhui, Fradkin Judith E
National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, 6100 Building Room 7B03, Bethesda, MD 20892, USA.
J Pediatr. 2004 Apr;144(4):430-6. doi: 10.1016/j.jpeds.2003.12.036.
Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions.
A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex.
There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000.
The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.
接受垂体来源生长激素（GH）治疗的患者死于克雅氏病的风险过高。我们调查了他们死于其他疾病，特别是可预防疾病的风险是否增加。
对已知的美国垂体来源GH接受者队列（N = 6107，治疗时间为1963 - 1985年）进行研究。通过医生、家长报告以及国家死亡指数确定死亡情况。将死亡率与按种族、年龄和性别标准化的美国人群预期死亡率进行比较。
从1963年到1996年，共有433例死亡，而预期死亡114例（相对风险[RR]为3.8；95%置信区间[CI]为3.4 - 4.2；P <.0001）。因任何肿瘤导致生长激素缺乏的受试者风险增加（RR为10.4；95%CI为9.1 - 12.0；P <.0001）。令人惊讶的是，出生后6个月内接受低血糖治疗的受试者风险极高（RR为18.3；95%CI为9.2 - 32.8；P <.0001），所有肾上腺功能不全的受试者也是如此（RR为7.1；95%CI为6.2 - 8.2；P <.0001）。所有死亡中有四分之一是突然且意外的。在26例克雅氏病病例中，自2000年以来有4例死亡。
垂体来源GH接受者的死亡率几乎是预期死亡率的四倍。用重组生长激素替代垂体来源生长激素仅消除了克雅氏病的风险。低血糖和肾上腺功能不全导致的死亡远多于克雅氏病。肾上腺功能不全和低血糖患者中大量潜在可预防的死亡凸显了肾上腺功能不全患者发生感染时早期干预以及积极治疗全垂体功能减退的重要性。
