Mortality not increased in patients with non-functional adrenal adenomas: a matched cohort study

CONTEXT: Mild autonomous cortisol secretion (MACS) is associated with increased mortality in patients with adrenal incidentalomas (AI), but little is known regarding the potential risk associated with non-functional adrenal adenomas (NFAA), which constitute the majority of AI.

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 two endocrine centres in southern Sweden because of an AI 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 was obtained from the Cause of Death Register. Patients were grouped according to cortisol level post 1-mg dexamethasone suppression test (cortisolDST) (<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 cortisolDST 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 inpatients younger than 65 years with cortisolDST 50-82 nmol/L compared to 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 AI while patients with MACS, and especially younger patients and those with cortisolDST ≥83 nmol/L, have significantly increased mortality risk compared to matched controls.