Mild autonomous cortisol secretion (MACS) is associated with increased mortality in patients with adrenal adenomas only in the presence of type 2 diabetes: a retrospective cohort study

Abstract Background Hypercortisolism and type 2 diabetes mellitus (T2D) independently contribute to an increased burden of cardiometabolic morbidity and mortality. However, data on the interaction of hypercortisolism and T2D are scarce—thus, we aimed to assess the cortisol-associated morbidity and mortality in the context of T2D and adrenal mild autonomous cortisol secretion (MACS). Methods This is a retrospective cohort study including 668 patients with adrenal adenomas, who were visiting the endocrine outpatient clinic at the Vienna General Hospital between 01.01.2000 to 31.12.2022. Of those, 151 were diagnosed with T2D at the time of their 1 mg dexamethasone suppression test (DST), other diabetes types were excluded. MACS was defined as a post 1 mg DST cortisol of > 1.8 µg/dL in the absence of Cushing’s stigmata and after biochemical exclusion of ACTH-dependency. The database was linked to the governmental death registry and patients alive after 01.12.2024 were censored. Kaplan Meier curves and cox proportional hazard models were analyzed via RStudio. Results Patients with T2D had a higher post 1 mg DST cortisol level and were more often diagnosed with hypertension, dyslipidemia and cardiovascular disease (CVD) compared to those without T2D. Compared to patients with non-functioning adrenal adenomas (NFAA) without T2D, MACS was strongly linked to increased mortality only in T2D (HR 2.51 [CI95% 1.41–4.48], p < 0.01) but not in those without T2D, even after adjustment for age, sex, BMI, smoking, hypertension, dyslipidemia and CVD at baseline. The T2D cohort with MACS had higher HbA1c and a 3-fold elevation in CVD prevalence compared to those without hypercortisolism. They did not differ according to age, sex or other cardiometabolic risk parameters (dyslipidemia, hypertension, BMI). Conclusions Among patients with adrenal adenomas, MACS is related to increased CVD prevalence and is associated with mortality in patients with T2D. These findings highlight the need for confirmatory prospective studies incorporating larger sample sizes to further assess the importance of earlier identification and treatment of MACS in patients with T2D.