Recruiting

Adrenalectomy & Semaglutide

Sponsor:

University of Texas Southwestern Medical Center

Code:

NCT07361874

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Autonomous Cortisol Secretion (ACS)

Subclinical Cushing's

Mild Autonomous Cortisol Excess

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Intervention 1: Adrenalectomy

Intervention 2: Semaglutide

Study Details

Brief summary:

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

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Autonomous Cortisol Secretion (ACS)

Subclinical Cushing's

Mild Autonomous Cortisol Excess

Study ID

NCT07361874

Start date

Mar 5, 2026

Status verified date

Mar, 2026

Completion date

May 31, 2030

Anticipated

Primary completion date

May 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

75 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm 1: Adrenalectomy (MACS)

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.

active comparator: Arm 2: Semaglutide (MACS)

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.

active comparator: Arm 3: Semaglutide (Matched Controls)

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.

Interventions

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.

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.

Primary outcome measure

  • Change in Insulin Sensitivity (M-value), mg/kg/min [ Time Frame: Baseline to Week 26 ]

Central Contacts and Locations

Central contacts

Oksana Hamidi, DO, MSCS

214-645-6397oksana.hamidi@utsouthwestern.edu

Locations

University of Texas Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

Oksana Hamidi, DO, MSCS

2146456397oksana.hamidi@utsouthwestern.edu

oksana.hamidi@utsouthwestern.edu

Principal Investigator:

Oksana Hamidi, DO, MSCS

More Information

Sponsor

University of Texas Southwestern Medical Center

Last update posted

Mar 27, 2026

Last verified

Mar, 2026

Keywords

  • Mild Autonomous Cortisol Secretion
  • MACS
  • Adrenal incidentaloma
  • Adrenal adenoma
  • Subclinical Cushing
  • Hypercortisolism
  • Cortisol dysregulation
  • Adrenalectomy
  • Semaglutide
  • Weight loss
  • Body composition
  • Insulin resistance
  • GLP-1 receptor agonist
  • Hyperinsulinemic-euglycemic clamp
  • Cortisol dynamics
  • Visceral fat
  • cardiometabolic risk
  • randomized controlled trial

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Texas Southwestern Medical Center on 2026-03-27.