Excess Mortality Associated With Hypopituitarism in Adults: A Meta-Analysis of Observational Studies
Excess Mortality Associated With Hypopituitarism in Adults: A Meta-Analysis of Observational Studies
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DOI：
10.1210/jc.2014-3787
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发表时间：
2015-04-01
影响因子：
5.8
通讯作者：
Clayton, Richard N.
中科院分区：
文献类型：
--
作者：
Pappachan, Joseph M.;Raskauskiene, Diana;Clayton, Richard N.
背景：先前的几项观察性研究表明垂体功能减退症与高死亡率之间存在关联。最近发表了关于GH替代降低标准死亡率比（SMR）的报告。目的：本荟萃分析评估了报告SMR的研究，以澄清低血压成人的死亡风险以及GH替代带来的潜在益处。数据来源：在Medline、Embase和科克伦图书馆进行了文献检索，截止日期为2014年3月31日。合格标准：研究与GH替代或不报告SMR与95%置信区间（95%CI）included.Data提取和分析：病人的特点，SMR数据，和治疗结果独立评估的两个作者，并与第三作者的共识，研究被选中进行分析。使用R中的统计软件包metafor对所有研究进行了荟萃分析，并对未使用和使用GH替代的研究分别进行了荟萃分析。结果：分析了6项研究，共报告了19153名垂体功能减退成年人，随访时间超过99000人年。垂体功能减退症与成人总体死亡率过高相关（加权SMR，1.99; 95%CI，1.21-2.76）。雌性低血压成年人的SMR高于雄性（2.53 vs 1.71）。垂体功能减退症的发病年龄越小，SMR越高。GH替代治疗改善了低血糖成人的死亡风险，与背景人群相当（GH替代治疗的SMR，1.15; 95% CI，1.05-1.24 vs无GH的SMR，2.40; 95% CI，1.46-3.34）。生长激素替代治疗对低血压妇女的死亡率的益处低于男性（SMR，1.57; 95%CI，1.38-1.77 vs 0.95; 95%CI，0.85-1.06）。局限性：从上市后数据来看，GH替代疗法的获益存在潜在的选择偏倚，需要从长期随机对照试验中获得进一步证据。垂体功能减退症可能会增加成人的过早死亡率。在垂体功能减退症中，GH替代治疗的死亡率获益在女性中不如男性明显。
Context: Several previous observational studies showed an association between hypopituitarism and excess mortality. Reports on reduction of standard mortality ratio (SMR) with GH replacement have been published recently.Objective: This meta-analysis assessed studies reporting SMR to clarify mortality risk in hypopituitary adults and also the potential benefit conferred by GH replacement.Data Sources: A literature search was performed in Medline, Embase, and Cochrane library up to March 31, 2014.Eligibility Criteria: Studies with or without GH replacement reporting SMR with 95% confidence intervals (95% CI) were included.Data Extraction and Analysis: Patient characteristics, SMR data, and treatment outcomes were independently assessed by two authors, and with consensus from third author, studies were selected for analysis. Meta-analysis was performed in all studies together, and those without and with GH replacement separately, using the statistical package metafor in R.Results: Six studies reporting a total of 19 153 hypopituiatary adults with a follow-up duration of more than 99 000 person years were analyzed. Hypopituitarism was associated with an overall excess mortality (weighted SMR, 1.99; 95% CI, 1.21-2.76) in adults. Female hypopituitary adults showed higher SMR compared with males (2.53 vs 1.71). Onset of hypopituitarism at a younger age was associated with higher SMR. GH replacement improved the mortality risk in hypopituitary adults that is comparable to the background population (SMR with GH replacement, 1.15; 95% CI, 1.05-1.24 vs SMR without GH, 2.40; 95% CI, 1.46-3.34). GH replacement conferred lower mortality benefit in hypopituitary women compared with men (SMR, 1.57; 95% CI, 1.38-1.77 vs 0.95; 95% CI, 0.85-1.06).Limitations: There was a potential selection bias of benefit of GH replacement from a post-marketing data necessitating further evidence from long-term randomized controlled trials.Conclusions: Hypopituitarism may increase premature mortality in adults. Mortality benefit from GH replacement in hypopituitarism is less pronounced in women than men.