OBJECTIVE To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). DESIGN Systematic review and meta-analysis. METHODS Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). RESULTS In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. CONCLUSIONS The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.

中文翻译：

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轻度自主皮质醇分泌的合并症和治疗效果：系统评价和荟萃分析。

目的 评估肾上腺偶发瘤和轻度自主皮质醇分泌 (MACS；> 1.8 µg/dL (>50 nmol/L) 皮质醇水平截止值 (1 mg 地塞米松后) 患者的 (1) 合并症和 (2) 治疗策略抑制试验）。设计 系统回顾和荟萃分析。方法 检索了截至 2022 年 7 月 14 日的七个数据库。符合条件的研究包括（随机）试验、队列研究和横断面研究，评估伴或不伴 MACS 的肾上腺偶发瘤患者可能因皮质醇过量或死亡引起的合并症，或评估MACS 的保守或手术治疗。进行随机效应荟萃分析来估计合并比例（95% CI）。结果 在 30 项横断面研究和 16 项队列研究中（总共 17 156 名患者），MACS 患者的糖尿病患病率较高（相对风险 [RR] 1.44 [1.23-1.69]）、高血压（RR = 1.24 [1.16]）。 -1.32]）和血脂异常（RR = 1.23 [1.13-1.34]）。在 4 项研究 (n = 5921) 中评估，MACS 患者的全因死亡率（根据混杂因素进行调整）增加（风险比 [HR] = 1.54 [1.27-1.81]）。九项观察性研究 (n = 856) 和 2 项随机试验 (n = 107) 表明糖代谢控制 (RR = 7.99 [2.95-21.90])、高血压 (RR = 8.75 [3.99-19.18]) 和血脂异常 (RR = 3.24 [1.19-8.82]) 肾上腺切除术后。结论 本系统评价和荟萃分析强调了 MACS 的相关性，因为与无功能偶发瘤患者相比，MACS 患者的心脏代谢发病率和死亡率似乎有所增加。然而，由于不同的定义、不同的结果、选择性报告和缺失数据，报告的汇总估计值需要谨慎解释。随机试验中患者数量较少，无法就 MACS 与这些合并症之间的因果关系得出强有力的结论。