IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes 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

NCT Number	NCT07361874
Lead Sponsor	University of Texas Southwestern Medical Center Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions	Mild Autonomous Cortisol Secretion (MACS), Autonomous Cortisol Secretion (ACS), Subclinical Cushing's, Mild Autonomous Cortisol Excess
Enrollment	75 participants
Start Date	2026-03-05
Primary Completion	2030-05-31 (estimated)
Study Completion	2030-05-31 (estimated)
Updated on ClinicalTrials.gov	2026-03-27