Mortality Not Increased in Patients With Nonfunctional Adrenal Adenomas: A Matched Cohort Study

CONTEXT: Mild autonomous cortisol secretion (MACS) is associated with increased mortality in patients with adrenal incidentalomas, but little is known regarding the potential risk associated with nonfunctional adrenal adenomas (NFAA), which constitute the majority of adrenal incidentalomas. OBJECTIVE: Compare mortality risk in patients with NFAA, and different levels of MACS, to matched controls. METHOD: This was a retrospective matched cohort study. All patients referred to 2 endocrine centers in southern Sweden because of an adrenal incidentaloma between 2005 and 2015 were enrolled. Controls (3:1) matched for sex, age, and residency were included. Primary endpoint was all-cause mortality. Outcome data were obtained from the Cause of Death Register. Patients were grouped according to cortisol level post 1-mg dexamethasone suppression test (cortisol(DST)) (<50 (NFAA), 50-82, 83-137, and ≥138 nmol/L). RESULTS: 1154 patients and 3462 matched controls were included. During a median follow-up of 6.6 years, 210 patients and 505 controls died. There were no statistically significant differences in mortality between patients with NFAA and their controls (HR 1.13 [0.87-1.46]) whereas mortality was increased compared to controls in patients with cortisol(DST) 83-137 (HR 1.99 [1.38-2.88]) and ≥138 nmol/L (HR 4.09 [2.41-6.93]). Likewise, the mortality risk was increased in patients younger than 65 years with cortisol(DST) 50-82 nmol/L compared with controls (HR 2.33 [1.30-4.17]). CONCLUSION: NFAA does not seem to pose a clinically relevant risk for increased mortality in patients with adrenal incidentalomas while patients with MACS, and especially younger patients and those with cortisol(DST) ≥83 nmol/L, have significantly increased mortality risk compared with matched controls.