The impact of mild autonomous cortisol secretion and proposed interventions.

Introduction: Mild autonomous cortisol secretion (MACS) is the most common hormonal alteration in patients with adrenal incidentalomas (AIs). Given its prevalence and associated adverse outcomes, reviewing its impact and interventions is essential.

Areas covered: In this article, we provide a comprehensive review on the diagnosis of MACS, the cardiometabolic burden associated with MACS and on its surgical and medical treatment. The diagnosis of MACS requires three criteria: hormonal evidence of hypercortisolism, the absence of typical Cushing's syndrome signs, and the presence of an AI. The most recommended test for MACS diagnosis is the 1 mg dexamethasone suppression test. There is plenty of evidence of the detrimental effect of MACS, including an increased risk of diabetes, hypertension, dyslipidemia and all-cause mortality. Surgery should be considered for patients with significant comorbidities and has been shown to significantly improve anthropometric variables, hyperglycemia and blood pressure. Medical therapy to lower cortisol offers an effective alternative, particularly for patients with bilateral AI, when surgery is contraindicated, or the patient declines surgery.

Expert opinion: Based on our expert opinion, steroid profiling has the potential to become the gold standard for MACS diagnosis, and further studies should identify which patients benefit most from specific treatment to guiding evidence-based recommendations.