Cushing disease (CD) is a life-threating disease, with increased mortality in comparison with the general population.
This study aimed to evaluate standardized mortality ratios (SMRs) in CD patients. We also analyzed independent risk factors related to increased mortality.
We conducted a longitudinal cohort study in a third level specialty center, from 1979 to 2018 in patients with CD.
From 1375 cases with pathology diagnosis of pituitary adenoma, 191 cases have the confirmed diagnosis of CD (14%). 172 patients completed follow-up, with a mean age at diagnosis of 33±11 years, female predominance (n=154, 89.5%), majority of them microadenoma (n=136, 79%), and a median follow-up of 7.5 years (2.4-15). Eighteen patients (10.5%) died; 8 of them (44%) with active CD, 8 (44%) under remission, and 2 (11%) under disease control. Estimated all-cause SMR=3.1, 95%CI 1.9-4.8, p <0.001. Cardiovascular disease was the main cause of death (SMR=4.2, 1.5-9.3, p=0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HR=5.2, IC95% 1.8-15.4, p=0.002), high cortisol levels after 1600 h at diagnosis (3.4, 2.3-7.0, p=0.02), and active CD (7.5, 3.8-17.3, p=0.003), significantly increased the risk of mortality.
Main cause of CD mortality was cardiovascular disease. Main risk factors for mortality were uncontrolled diabetes, persistently high cortisol levels after 1600 h at diagnosis, and active disease at last follow-up.

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