Mortality risk and causes of death in exogenous Cushing's syndrome: a systematic review and meta-analysis.

Although long-term GC exposure causes systemic toxicity, the magnitude, dose-response relationship, and causes of GC-associated mortality remain incompletely defined.

尽管长期暴露于GCs会导致全身性毒性，但GC相关死亡的规模、剂量-反应关系和原因尚不完全清楚。

Background

To quantify overall and cause-specific mortality associated with chronic oral GC exposure and evaluate dose-response relationships across underlying disease groups.

为了量化与慢性口服糖皮质激素暴露相关的总死亡率和特定死因死亡率，并评估不同基础疾病组之间的剂量-反应关系。

Methods

We conducted a systematic reviewand meta-analysisfollowing PRISMA guidelines (PROSPERO CRD42017067530).

我们遵循PRISMA指南进行了系统评价和荟萃分析（PROSPERO CRD42017067530）。

PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, and CINAHL were searched from 1945 to March 2019.

从1945年到2019年3月，对PubMed/MEDLINE、EMBASE、Cochrane图书馆、Web of Science和CINAHL进行了检索。

Eligible studies reported standardized mortality ratios (SMRs) or absolute deaths among adults receiving chronic oral GCs.

符合条件的研究报告了接受慢性口服糖皮质激素治疗的成年人的标准死亡率比（SMRs）或绝对死亡人数。

Random-effects meta-analysisand mixed-effects meta-regression were used to synthesize mortality and dose-response associations across GC exposure metrics, exposure duration, and disease subgroups.

随机效应元分析和混合效应元回归被用于综合胃癌暴露指标、暴露时长和疾病亚组的死亡率和剂量反应关系。

Results

One-hundred and sixteen studies encompassing 128 cohorts and 51 380 patients were included.

共纳入了116项研究，涵盖128个队列和51,380名患者。

Chronic GC exposure was associated with excess mortality (pooled SMR 1.87; 95%CI 1.32-2.61; I2 74.0%).

慢性胃癌暴露与过量死亡率相关（汇总标准化死亡比 1.87；95% 置信区间 1.32-2.61；I2 74.0%）。

The pooled proportion of death was 12.0% (95%CI 10-14%).

死亡的汇总比例为 12.0%（95% 置信区间 10-14%）。

Mortality risk was highest in inflammatory diseases (30.0%) and the vasculitides (18.0%).

炎症性疾病（30.0%）和血管炎（18.0%）的死亡风险最高。

Higher cumulative dose (≥5 g prednisolone-equivalent), average daily dose >5 mg/day, and higher initial dose were each independently associated with increased mortality.

较高的累积剂量（≥5克泼尼松当量）、平均每日剂量超过5毫克以及较高的初始剂量，每个都独立地与增加的死亡率相关。

Cardiovascular disease was the leading causes of death (25.6%), followed by malignancy (15.7%) and infection (13.4%).

心血管疾病是主要的死亡原因（25.6%），其次是恶性肿瘤（15.7%）和感染（13.4%）。

Conclusions

Chronic oral GC exposure was associated with increased mortality across disease groups, with higher cumulative and early-treatment doses correlating with higher risk.

长期口服糖皮质激素暴露与各疾病组死亡率增加有关，累积剂量和早期治疗剂量较高与更高的风险相关。

However, causal attribution remains uncertain due to confounding by indication, limited disease-severity data, and exposure misclassification.

然而，由于指示混杂、疾病严重程度数据有限以及暴露分类错误，因果归属仍然不确定。

These findings support GC stewardship and targeted cardiovascular and infection risk mitigation, rather than indiscriminate dose reduction.

这些发现支持胃肠道保护策略和针对性的心血管及感染风险缓解，而不是不加区分的剂量减少。

However, causal attribution remains uncertain due to confounding by indication, limited disease-severity data, and exposure misclassification.

然而，由于指示混杂、疾病严重程度数据有限以及暴露分类错误，因果归属仍然不确定。