Non-Functional Adrenal Tumors and Incident Cardiometabolic Outcomes

Abstract

Background: Adrenal tumors are incidentally discovered on abdominal imaging with increasing frequency. Small cross-sectional studies have shown that non-functional adrenal tumors have a higher prevalence of cardiovascular risk factors. However, longitudinal studies are lacking. We hypothesized that non-functional adrenal tumors (NFAT) may increase the risk for incident cardiovascular and metabolic outcomes when compared to controls without adrenal tumors. Methods: We conducted a retrospective longitudinal cohort study. We identified patients who underwent abdominal imaging between 1991-2014 (n=234,267). After a rigorous exclusion process, cases of NFAT were selected using medical chart review to confirm adrenal tumor on imaging and the absence of adrenal hormone dysfunction or malignancy (n=242). Controls were computer-matched by age, gender, and race after confirming no adrenal hormone dysfunction or neoplasia on imaging (n=1237). Multivariable Cox proportional hazards regression was used to evaluate the association between NFAT and the risk of developing incident clinical outcomes in participants with >3 years of follow-up. Results: NFAT were associated with a significantly higher hazard for incident composite diabetes when compared to no adrenal tumor (adjusted HR=2.36, 95% CI: 1.45, 3.84). Larger NFAT size strongly associated with higher “normal” cortisol levels following 1 mg of dexamethasone (<1.8 mcg/dL) (P<0.0001) and higher “normal” 24h urinary cortisol levels (<50 mcg/24h) (P<0.0001). Higher “normal” cortisol levels following dexamethasone predicted a higher prevalence of type 2 diabetes among participants with NFAT, P-trend=0.04. Conclusions: NFAT were associated with a greater than twofold increased risk of developing diabetes when compared to no adrenal tumor. Since “non-functional” adrenal tumors are common and considered to pose no health risk, these results prompt a re-assessment of how incidentally discovered adrenal tumors are biochemically assessed and subsequently treated.