Frontiers in Endocrinology · Nov 4, 2026
Mild Autonomous Cortisol Secretion: Current Concepts and Clinical Implications
By Anna Golara, Bartosz Kiedrowicz, Robert Stasiuk et al.
Background: Mild autonomous cortisol secretion (MACS), previously referred to as subclinical Cushing's syndrome, represents a state of biochemical cortisol excess without the overt clinical symptoms of Cushing's syndrome. It is most commonly detected in patients with adrenal incidentalomas. Recent European Society of Endocrinology (ESE) guidelines have refined the definition and diagnostic thresholds, highlighting the clinical relevance of this condition. Epidemiology and pathophysiology: MACS is identified in approximately 20–30% of patients with adrenal incidentalomas, with prevalence increasing with age. Autonomous cortisol secretion results from adrenal adenomas or hyperplasia, leading to partial suppression of the hypothalamic–pituitary– adrenal (HPA) axis. Clinical consequences: Although often clinically silent, MACS is associated with an increased prevalence of metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, and metabolic dysfunction–associated steatotic liver disease. Cardiovascular morbidity and mortality are consistently higher compared to patients with non-functioning adenomas. Other reported complications include impaired kidney function, reduced bone mineral density, increased fracture risk, and impaired quality of life. Diagnosis and management: Diagnosis is based primarily on post-dexamethasone cortisol suppression test thresholds, supported by additional biochemical and imaging parameters. Management strategies remain debated, ranging from careful observation with optimization of metabolic, organ and mental risk factors to surgical adrenalectomy in selected patients. Several studies suggest that surgery may improve metabolic outcomes and quality of life, but evidence suggests benefit only in selected patients. Conclusions: MACS represents a common and clinically relevant condition with significant cardiometabolic implications. Current evidence supports a personalized approach to management, considering patient comorbidities, age, and surgical risk. Further prospective studies are warranted to clarify long-term outcomes and to refine treatment algorithms.