Adrenalectomy; Status, Mild Autonomous Cortisol Secretion (MACS)
Conditions
Keywords
adrenalectomy, MACS, mild autonomous cortisol secretion
Brief summary
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.
Detailed 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.
Interventions
DRUGTirzepatide
Tirzepatide will be initiated at the lowest 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.
OTHERStandard medical treatment
Participants will receive postoperative care and follow up per institutional standard-of-care practices
Sponsors
Alaa Sada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in systolic blood pressure | Baseline and 12 months | Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| weight | Baseline and 12 months | Change in participant weight, Kg |
| medication | Baseline and 12 months reported in WHO defined daily doses (DDDs) | any change in medication expressed as defined daily doses (DDDs) |
| HbA1c | Baseline and 12 months | change in HbA1c levels |
| quality of life metrics | Baseline and 12 months | quality of life metrics will measured using the 36-Item Short Form Health Survey (SF-36) which is a validated measure of health-related quality of life assessing eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 to 100, with higher scores indicating better health status. Domain scores may be analyzed individually or combined using standard scoring algorithms to generate the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, which are norm-based (mean 50, SD 10); higher values reflect better physical and mental health, respectively. |
| BMI | Baseline and 12 months | Any change in BMI in kg/m2 |
Countries
United States
Contacts
CONTACTMeghan Kelley
PRINCIPAL_INVESTIGATORAlaa Sada, MD
University of Pittsburgh
Outcome results
None listed