Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion

Alaa Sada

Status and phase: Enrolling; Phase 2

Conditions: Mild Autonomous Cortisol Secretion (MACS); Adrenalectomy; Status

Treatments: Drug: Tirzepatide; Other: Standard medical treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT07573163

STUDY25030073

Details and patient eligibility

About

Mild Autonomous Cortisol Secretion (MACS) is a condition in which an adrenal gland produces excess cortisol and is associated with high blood pressure, diabetes, and weight gain. Surgical removal of the adrenal gland (adrenalectomy) is standard treatment, but some patients continue to have metabolic health problems after surgery.

This randomized study will evaluate whether treatment with tirzepatide after adrenalectomy improves metabolic outcomes in patients with MACS compared with adrenalectomy alone.

Full description

This prospective, randomized study will enroll adults with MACS and elevated blood pressure who are undergoing unilateral adrenalectomy. Following surgery, participants will be randomized in a 1:1 ratio to one of two groups: adrenalectomy alone or adrenalectomy followed by tirzepatide therapy for 12 months. Tirzepatide will be prescribed and managed by the study team in accordance with current standard-of-care practices, including routine clinical monitoring and dose adjustments.

The primary focus of the study is to evaluate blood pressure control at 12 months. Secondary outcomes include change in body weight, body mass index, glycemic control, medication burden, and patient-reported quality of life. This study aims to generate preliminary data on the feasibility, safety, and potential additive metabolic benefits of combining pharmacologic incretin-based therapy with surgical management of MACS.

Enrollment: 34 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults aged 18 years and older
• Diagnosis of MACS, defined as morning cortisol >1.8 mcg/dL after a 1 mg dexamethasone suppression test
• Elevated blood pressure (SBP ≥120 mmHg or DBP ≥80 mmHg per the 2025 American College of Cardiology/American Heart Association [ACC/AHA] criteria, or current use of antihypertensive medication)
• BMI ≥27
• Undergoing or having undergone adrenalectomy for the treatment of MACS

Exclusion criteria

• Bilateral adrenal lesions
• Adrenal malignancy
• Concurrent primary aldosteronism with MACS
• Current use of GLP-1 receptor agonists
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
• Pregnancy or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 2 patient groups

GLP-1 Treatment

Active Comparator group

Description:

GLP-1 dose of 2.5 mg once weekly for 4 weeks. The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.

Treatment:

Drug: Tirzepatide

Standard of Care arm

Active Comparator group

Description:

Participants in this arm will receive standard of care management for as determined by their treating clinician.

Treatment:

Other: Standard medical treatment