英国特伦特河畔斯托克库欣病50年死亡率和发病率研究及文献荟萃分析

Mortality and Morbidity in Cushing"s Disease over 50 Years in Stoke-on-Trent, UK: Audit and Meta-Analysis of Literature

英国特伦特河畔斯托克库欣病50年死亡率和发病率研究及文献荟萃分析海南医学院附属医院内分泌科王新军

Context: Pituitary ACTH-dependent Cushing"s disease (CD) is uncommon, and there are very limited data on long-term mortality.

背景：垂体ACTH依赖性库欣病（CD）罕见，关于其长期死亡率的数据非常有限。

Objective: The aim was to summarize what is known about mortality in ACTH-dependent CD, to report on our own data, and to provide a meta-analysis of six other reports that addressed mortality of CD.

目的： 本研究目的是总结我们所知道的促肾上腺皮质激素依赖性库欣病的死亡率，报告我们的数据，并对其他六项关于库欣病死亡率的报告进行荟萃分析。

Design and Methods: Vital status of 60 CD patients was recorded as of December 31, 2009, and the standardized mortality ratio (SMR) was calculated and compared with the general population of England and Wales, United Kingdom. A meta-analysis of SMRs from seven studies (including ours) was performed for overall mortality in CD. Where reported (four studies), a similar meta-analysis was performed for those patients whose hypercortisolism was in remission after treatment compared to those patients from the same center with persistent disease.

设计和方法：2009年12月31日记录了 60例库欣病患者的生存状态，计算标准化死亡率（SMR），并与英格兰、威尔士和英国总人口进行比较。对7项关于库欣病的整体死亡率进行荟萃分析（包括我们）。经治疗高皮质醇血症缓解以后的患者进行荟萃分析，并与同一中心的持续性疾病患者进行比较。
Results: 1. From Stoke-on-Trent, 51 of 60 patients were female, median age at diagnosis was in the range of 36?46 yr, and median follow-up was 15 yr. There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the whole cohort was 4.8 (95% confidence interval, 2.8?8.3) (P < 0001). SMR for vascular disease was 13.8 (7.2?36.5) (P < 0001). For persistent disease (n = 6), SMR was 16 (6.7?38.4) vs. remission (n = 54) SMR of 3.3 (1.7?6.7); after adjustment for age and sex, relative risk of death for persistent disease was 10.7 (2.3?48.6) (P = 0.002). Hypertension and diabetes mellitus were associated with significantly worse survival. 2. Using a random effects model meta-analysis revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45?3.41) (P < 0.001). Pooled SMR was 1.2 (0.45?3.2) (P = not significant) for patients in remission and 5.5 (2.7?11.3) (P = 0.001) for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes are the main determinants of mortality.

结果：1. 特伦特河畔斯托克的患者，60例患者中51例为女性，诊断时中位年龄范围为36-46岁，中位随访时间为15年。共有13人死亡，9例死于心血管疾病。整个队列总体SMR为4.8（95％可信区间：2.8~8.3）（P <0001）。血管疾病的SMR为13.8（7.2~36.5）（P <0001）。对于持久性疾病患者（6例），SMR为16（6.7~38.4），而缓解组（n = 54）SMR为3.3（1.7-6.7）；校正年龄和性别后，持久性疾病患者相对死亡的风险为10.7 （2.3~48.6）（p= 0.002）。高血压和糖尿病都与疾病恶化显著相关。 2. 采用随机效应模型荟萃分析显示，整体SMR（缓解者及持续性疾病者）为2.2（1.45~3.41）（P < 0.001）。汇集SMR在缓解患者为1.2（0.45~3.2）（P值不显著），在持续性疾病患者为5.5（2.7~11.3）（P = 0.001）。持久性疾病、诊断时的年龄、高血压和糖尿病是死亡的主要决定因素。
Conclusions: Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

结论： 库欣病的整体死亡率是普通人群的两倍。然而，随着库欣病患者缓解，预后明显要比持续高皮质醇血症患者要好，他们似乎死亡率没有增加。高血压和糖尿病是雨后不良的危险因素。由于病人的诊断和治疗时较年轻，缓解患者需要进行更长期的随访观察，才能得出他们的死亡率与总人口没有明显不同，特别是因为即使疾病的生化控制成功以后，心血管危险因素可能持续存在。

J Clin Endocrinol Metab 2011 96: 632-642