RECRUITINGINTERVENTIONAL

IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion

IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion

About This Trial

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

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - Prior GLP-1 RA within 90 days - Weight change \>5 kg in past 90 days - Prior obesity/diabetes surgery - Type 1 diabetes or other diabetes types - Severe organ disease - Recent pancreatitis - Pregnancy, breastfeeding - Contraindication to semaglutide - Contraindication to surgery delay - Chronic glucocorticoid use Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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 Exclusion Criteria: * Prior GLP-1 RA within 90 days * Weight change \>5 kg in past 90 days * Prior obesity/diabetes surgery * Type 1 diabetes or other diabetes types * Severe organ disease * Recent pancreatitis * Pregnancy, breastfeeding * Contraindication to semaglutide * Contraindication to surgery delay * Chronic glucocorticoid use

Treatments Being Tested

PROCEDURE

Intervention 1: Adrenalectomy

Surgical removal of one adrenal gland performed by an endocrine surgeon following institutional standard-of-care practices. Includes postoperative monitoring for adrenal insufficiency and routine clinical follow-up.

DRUG

Intervention 2: Semaglutide

Once-weekly subcutaneous semaglutide administered according to FDA-approved titration for chronic weight management (0.25 mg to 2.4 mg weekly as tolerated). Participants receive training on injection technique, dose escalation, and safety monitoring.

Locations (1)

University of Texas Southwestern Medical Center

Dallas, Texas, United States