Surgery or semaglutide for mild autonomous cortisol secretion
Compares adrenal gland removal with semaglutide for insulin resistance in adults with mild cortisol excess.
Key facts
- Who runs it
- University of Texas Southwestern Medical Center
- Where
- Dallas, United StatesSee the site
- Trial code
- Registry title
- IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion
- Status
- Recruiting
- People taking part
- 75 people, planned
- Started
- 5 Mar 2026
- Expected to end
- 31 May 2030
- Type of study
- Interventional, 3 groupsOne group gets an existing treatment, for comparison.
- Treatments tested
- Intervention 1: Adrenalectomy
- Intervention 2: Semaglutide
- Record updated
- 27 March 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with mild autonomous cortisol secretion (MACS), a small adrenal tumour making extra cortisol. It also takes adults without adrenal problems who are overweight and have other heart or metabolic conditions, for comparison.
- Age
- 18 years and older.
- Sex
- All sexes can join.
- Disease stage
- MACS group: an adrenal adenoma (a benign adrenal tumour), no full Cushing syndrome, and fit enough to have adrenalectomy. People must be willing to delay surgery 6 months if assigned to the drug. Comparison group: no adrenal problems, BMI ≥27 and ≥2 cardiometabolic conditions.
- Earlier treatment
- Medicine doses must be stable for ≥4 weeks. No GLP-1 RA drug within 90 days. No past obesity or diabetes surgery. No long-term glucocorticoid (steroid) use.
- Biomarker or test result
- MACS group: cortisol >1.8 µg/dL after a dexamethasone suppression test (DST). Comparison group: normal DST. Negative pregnancy test if applicable.
Main reasons for not taking part
- Weight change of more than 5 kg (11 lb) in the past 90 days
- Type 1 diabetes or other types of diabetes
- Severe organ disease or recent pancreatitis
- Pregnancy or breastfeeding
- Cannot take semaglutide or cannot safely delay surgery
The registry criteria, word for word
Show all 16 criteriaShow less
Who can take part
- 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 cannot take part
- Prior GLP-1 RA within 90 days
- Prior obesity/diabetes surgery
- Contraindication to surgery delay
- Type 1 diabetes or other diabetes types
- Severe organ disease
- Weight change >5 kg in past 90 days
- Recent pancreatitis
- Pregnancy, breastfeeding
- Contraindication to semaglutide
- Chronic glucocorticoid use
Where in United States
- University of Texas Southwestern Medical CenterDallas, United StatesContact: Oksana Hamidi, DO, MSCSTaking people
About the trial
What the trial wants to find out
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.
Read full original descriptionShow less
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
The 3 groups in the trial
- Arm 1: Adrenalectomy (MACS)Existing treatment, for comparison
Adults with mild autonomous cortisol secretion (MACS) who are clinically eligible for adrenalectomy undergo unilateral adrenalectomy as part of standard care. Participants complete all metabolic assessments before and after treatment.
Treatment: Intervention 1: Adrenalectomy
- Arm 2: Semaglutide (MACS)Existing treatment, for comparison
Adults with MACS receive once-weekly semaglutide for 26 weeks using FDA-approved weight-management dosing. Participants undergo the same assessments as the surgery group.
Treatment: Intervention 2: Semaglutide
- Arm 3: Semaglutide (Matched Controls)Existing treatment, for comparison
Matched adults without adrenal tumors receive semaglutide using the same dosing schedule as MACS participants. This arm allows comparison of semaglutide responses between individuals with and without cortisol dysregulation.
Treatment: Intervention 2: Semaglutide
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion
- Plain-language title
- Surgery or semaglutide for mild autonomous cortisol secretionGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 14 November 2026.
- Record updated
- 27 March 2026