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The effect of endogenous Cushing's syndrome on all-cause and cause-specific mortality

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  • Chief Cushie



We aimed to perform a systematic review and meta-analysis of all-cause and cause-specific mortality of patients with benign endogenous Cushing's syndrome (CS).


The protocol was registered in PROSPERO (CRD42017067530). PubMed, EMBASE, CINHAL, Web of Science and Cochrane Central searches were undertaken from inception to January 2021. Outcomes were the standardized mortality ratio (SMR), proportion and cause of deaths. The I 2 test, subgroup analysis and meta-regression were used to assess heterogeneity across studies.


SMR was reported in 14 articles including 3,691 patients (13 Cushing's disease (CD) and 7 adrenal CS (ACS) cohorts). Overall SMR was 3.0 (95%CI 2.3-3.9; I 2=80.5%) for all CS, 2.8 (95%CI 2.1-3.7 I 2=81.2%) for CD and 3.3 (95%CI 0.5-6.6; I 2=77.9%) for ACS. Proportion of deaths, reported in 87 articles including 19,181 CS patients (53 CD, 24 ACS, and 20 combined CS cohorts) was 0.05 (95%CI 0.03, 0.06) for all CS subtypes with meta-regression analysis revealing no differences between CS subtypes (P=0.052). The proportion of deaths was 0.1 (10%) in articles published before 2000 and 0.03 (3%) in 2000 until the last search for CS (P<0.001), CD (p<0.001), and ACS (P=0.01). The causes of death were atherosclerotic diseases and thromboembolism (43.4%), infection (12.7%), malignancy (10.6%), active disease (3.5%), adrenal insufficiency (3.0%), and suicide (2.2%).

Despite improved outcomes in recent years, increased mortality from CS persists. The causes of death highlight the need to prevent and manage co-morbidities in addition to treating hypercortisolism.

Information Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.
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© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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