Protocol for Systematic Scoping Review Medical interventions for mild autonomous cortisol excess (MACS)

Adrenal incidentalomas (AI) are commonly detected upon cross sectional imaging of the abdomen for reasons other than to assess the adrenal glands. The majority of AI are benign adrenocortical adenomas. These adenomas are common and occur in up to 10% of the population aged over 80. Approximately 30-50% of adrenocortical adenomas secrete excess cortisol, independently of the normal hypothalamic-pituitary regulation termed mild autonomous cortisol secretion (MACS) (Fassnacht 2023). Previously named subclinical Cushing’s due to the lack of classical features associated with Cushing’s syndrome, MACS has been demonstrated to be associated with a significantly increased risk of cardiometabolic morbidity and mortality (Pelsma 2023). Although several small studies have used medical therapy in MACS, there are currently no licensed medications, with standard of care being conservative management of comorbidities or laparoscopic adrenalectomy in select cases following multi-disciplinary team discussion (Fassnacht 2023). We aim to systematically review the evidence for the effectiveness of medical interventions for MACS in improving patient outcomes.