ENDO 2013：库欣综合征死亡率的流行病学调查（MISSION研究）

    第95届美国内分泌学会年会（ENDO2013）于2013年6月15-18日在美国旧金山隆重举行。大会旨在为内分泌领域研究人员提供最前沿的科学知识与技术，包括基础和临床研究。本次大会参会人数达9300位，创ENDO年会历史新高，共收到摘要约2600份，ENDO2013希望与会者能从中获得有价值的教育内容和发现新的有启发性的想法以促进临床实践。

    一项由全球多国共同发起的大样本量研究——MISSION研究证实，库欣综合征(Cushing’s syndrome,  CS)患者的死亡率与疾病活动状态和合并症(主要是葡萄糖代谢受损、心脏病及感染)密切相关。
     库欣综合征(Cushing’s syndrome,  CS)患者的死亡率是正常人的5倍。MISSION研究是一项回顾性研究，旨在采用涵盖所有类型CS的大样本量患者人群评估库欣综合征的死亡率。研究的主要目的是发现所有受试者与死亡相关的危险因素及合并症和计算患者的生存曲线。
MISSION研究纳入全球范围内共4872名患者(1004名男性和3868名女性)。最常见的是垂体性CS(68.5%)，其次是肾上腺疾病引起的CS(14.9%)和异位CS(4.7%)。不明原因CS达6.1%。此外，20.9%的患者处于病情活动期，79.1%病情稳定[包括短期缓解(31.8%)、长期治愈(40.4%)和药物控制(6.7%)的患者]。
    结果显示，累积粗死亡率为6.86人/1000/年，男性患者显著高于女性(11.4 vs 5.82,  p<0.001)。处于活动期的CS患者，其累积粗死亡率显著高于其他病情组：前者的死亡率是24.45，而缓解组、治愈组及药物控制组的死亡率分别是4.83、2.43和6.4。与CS缓解组及药物控制组的患者相比，治愈组的粗死亡率显著降低(p<0.001)。与垂体和肾上腺来源的CS患者相比，异位CS患者粗死亡率更高(31.15  vs 4.25,  p<0.001)。而垂体和肾上腺来源的CS患者之间，死亡率无显著差异。CS危险因素及合并症对死亡率有很重要的影响。与无合并症的患者相比，有以下合并症的患者死亡率更高：合并高血压者  (8.52 vs 2.73, p < 0.0001), 葡萄糖代谢受损11.08 vs 4.39, p < 0.0001);血脂异常(7.92 vs  5.99, p < 0.01);凝血病(11.1 vs 6.3,p < 0.01);心脏病(14.5 vs 5.3, p <  0.0001)和感染(15.11 vs 4.74, p < 0.0001)。

【研究摘要】
MISSION STUDY. A worldwide epidemiological study on the mortality  associated with Cushing’s syndrome performed in nearly 5000  patients

Rosario Pivonello*1, Pasquale Vitale2, Lorenzo  Mantovani3, Roberta Ciampichini4, Galina A  Melnichenko5, Sabina Zacharieva6, Feng Gu7,  Oscar Domingo Bruno8, Nalini Shah9 and Annamaria  Colao10

1Federico II University, 2University Federico II,  Naples, Italy, 3University Federico II, 4CHARTA  Foundation, Milan, Italy, 5Endocrinology Res Ctr, Moscow, Russia,  6Medical University, Sofia, Bulgaria, 7Peking union    Medical College Hospital, Beijing, China, 8Hospital de Clinicas,  Buenos Aires, Argentina, 9KEM Hospital, Mumbai,  India,10Università Federico II di Napoli, Naples, Italy

Background: Cushing’s syndrome (CS) is associated with an  increased mortality, which is up to 5 times higher than in normal population.  MISSION study is a retrospective study focusing on the evaluation of the  mortality in a very large population of patients with all types of CS.
Aim: The main objective of the study consists in the  calculation of the risk factors and complications related mortality rate and  survival curve of patients included in the study.

Patients and method: 4872 worldwide patients (1004 males and  3868 females entered the study. Pituitary-derived CS (68.5%) largely represented  the most common form of the disease, followed by adrenal (14.9%) and ectopic  (4.7%) CS. Occult and unknown origins amounted to 6,1% of cases. Moreover, 20.9%  of patients showed active disease, whereas the remaining 79.1% had inactive  disease, including patients evaluated after short-term remission (31.8%) or  long-term cure (40.4%) and patients under pharmacological control (6.7%).

Results: The cumulative crude mortality rate was 6.86 per  1000 person-years; it was significantly higher in men than in women (11.4 vs  5.82, p<0.0001). Patients with active disease had a crude mortality rate  significantly higher compared with patients in different disease status: crude  mortality rate was 24.45 in patients with active disease and 4.83, 2.43 and 6.40  (p<0.001) in patients in remission, or cured patients or under pharmacologic  control, respectively. Cured patients had lower crude mortality rate compared  with patients in remission and those under pharmacologic control (p<0.001).  Furthermore, a worse crude mortality rate was registered in patients with  ectopic compared with those with pituitary (31.15 vs 4.25, p<0,001) and  adrenal (3,21, p<0,001) disease while no statistically significant difference  was found between patients with pituitary and adrenal disease. Finally, the  analyzed risk factors or complications demonstrated to have an important impact  on the mortality of patients with CS. In particular, mortality rate was higher  in patients with hypertension (8.52 vs 2.73, p<0.0001), impairment of glucose  metabolism (11.08 vs 4.39, p<0.0001); dyslipidemia (7,92 vs 5,99, p<0,01),  coagulopathy (11.1 vs 6,3, p<0,01), cardiopathy (14.5 vs 5.3, p<0.0001)  and infections (15.11 vs 4.74, p<0.0001) compared with patients without the  specific complications. {nextpage}

Conclusion: The results of the current study performed in a  very large number of patients derived by several country in the world  demonstrated that the mortality associated with CS is strongly related to the  disease activity and to their complications, mainly the impairment of glucose  metabolism, cardiopathy and infections.