Cardiometabolic Risk in Bilateral vs Unilateral Nonfunctioning Adrenal Incidentalomas: Evidence From a Large Referral Center Cohort

Objective: The cardiometabolic risk associated with nonfunctioning adrenal incidentalomas (NFAIs) remains controversial. This study aimed to compare cardiovascular risk and related complications in patients with bilateral versus unilateral NFAIs. Methods: This is a retrospective cross-sectional study including outpatients from a tertiary referral center. The cardiovascular risk was assessed using validated scores, and data about the presence of cardiometabolic complications and organ damage were collected. Results: We included 906 patients with NFAIs in primary cardiovascular prevention (820 unilateral, 86 bilateral), diagnosed and treated in our center between 2000 and 2024. Multivariable linear regressions showed that bilateral NFAIs are associated with higher cardiovascular risk, compared to unilateral NFAI, when calculated using the Framingham score (p=0.006), the CUORE Project (p<0.001), the SCORE (p<0.001), and the SCORE-2 (p=0.035). While multivariable logistic regressions revealed that patients with bilateral NFAIs are associated with the presence of type 2 diabetes mellitus (OR 2.36, 95% CI 1.18-4.72; p=0.015) and with the presence of organ damage (OR 2.09, 95% CI 1.00-4.37; p=0.050), after adjusting for age, male sex, body mass index, smoking habit, arterial hypertension and number of antihypertensive drugs; estimated glomerular filtration rate was additionally included as a covariate in the model predicting type 2 diabetes mellitus. Conclusions: Bilateral NFAIs are independently associated with greater cardiometabolic risk and complications compared to unilateral lesions. These findings support the concept of bilaterality as a distinct clinical phenotype and suggest that patients with bilateral NFAIs may benefit from closer cardiometabolic monitoring.