IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion
The goal of this study is to learn how two treatments-adrenalectomy (surgical removal of an adrenal gland) and semaglutide (a medication used for weight management)-affect insulin resistance and cortisol regulation in adults with mild autonomous cortisol secretion (MACS). The study will also learn how these treatments impact body composition, blood pressure, cholesterol, inflammation, muscle strength, and quality of life. The main questions the study aims to answer are: 1. Does adrenalectomy or semaglutide improve insulin resistance more in people with MACS? 2. How do these treatments change cortisol patterns and other cardiometabolic risk factors? 3. Do people with MACS respond differently to semaglutide compared to matched adults without MACS? Participants will: 1. Receive either adrenalectomy or semaglutide if they have MACS, or semaglutide if they are matched controls 2. Complete clinic visits and phone visits over about 26-30 weeks 3. Undergo metabolic testing such as blood tests, urine steroid profiling, body composition scans, blood pressure monitoring, muscle strength testing, and questionnaires about health and well-being
• Adults ≥18 years
• MACS groups: adrenal adenoma + DST cortisol \>1.8 µg/dL + no overt Cushing + eligible for adrenalectomy
• Willingness to postpone surgery 6 months if randomized
• Controls: no adrenal abnormalities + normal DST + BMI ≥27 + ≥2 cardiometabolic conditions
• Stable medication doses for ≥4 weeks
• Negative pregnancy test if applicable