DRUG
Tirzepatide
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.
Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion
Status
Recruiting
Phase
Phase 2
Enrollment
34
Locations
1
Results
Not posted
Publications
12
Study summary
What the protocol is testing.
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 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
Treatment arms and agents.
OTHER
Standard medical treatment
Participants will receive postoperative care and follow up per institutional standard-of-care practices
Timeline
From registration to results.
First posted
May 7, 2026
Study start
Jul 27, 2026
Primary completion
Jul 31, 2028
Study completion
Dec 31, 2028
Results posted
Not reported
Registry updated
Jul 30, 2026
Outcomes
What the study measures.
Primary outcomes
Change in systolic blood pressure
Time frame · Baseline and 12 months
Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg
Secondary outcomes
weight
Time frame · Baseline and 12 months
Change in participant weight, Kg
medication
Time frame · Baseline and 12 months reported in WHO defined daily doses (DDDs)
any change in medication expressed as defined daily doses (DDDs)
HbA1c
Time frame · Baseline and 12 months
change in HbA1c levels
quality of life metrics
Time frame · 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
Time frame · Baseline and 12 months
Any change in BMI in kg/m2
Eligibility
Who can take part.
- Minimum age
- 18 Years
- Maximum age
- Not reported
- Sex
- ALL
- 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
Study locations
1 registered sites.
United States. Showing up to 24 locations stored in the fast local snapshot.
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Publications
Results and literature.
PMID 37700437 ↗Kanbay M, Copur S, Siriopol D, Yildiz AB, Gaipov A, van Raalte DH, Tuttle KR. Effect of tirzepatide on blood pressure and lipids: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023 Dec;25(12):3766-3778. doi: 10.1111/dom.15272. Epub 2023 Sep 12.PMID 39084707 ↗Krumholz HM, de Lemos JA, Sattar N, Linetzky B, Sharma P, Mast CJ, Ahmad NN, Bunck MC, Stefanski A. Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial. Heart. 2024 Sep 16;110(19):1165-1171. doi: 10.1136/heartjnl-2024-324170.PMID 19632967 ↗Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D, Fishman E, Kharlip J; American Association of Clinical Endocrinologists; American Association of Endocrine Surgeons. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009 Jul-Aug;15 Suppl 1:1-20. doi: 10.4158/EP.15.S1.1. No abstract available.PMID 37801655 ↗Pelsma ICM, Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis. Eur J Endocrinol. 2023 Oct 17;189(4):S88-S101. doi: 10.1093/ejendo/lvad134.PMID 35799460 ↗Vanek C, Loriaux L. The 1 mg overnight dexamethasone suppression test: a danger to the adrenal gland? Curr Opin Endocrinol Diabetes Obes. 2022 Aug 1;29(4):403-405. doi: 10.1097/MED.0000000000000752.PMID 32206602 ↗Kelsall A, Iqbal A, Newell-Price J. Adrenal incidentaloma: cardiovascular and metabolic effects of mild cortisol excess. Gland Surg. 2020 Feb;9(1):94-104. doi: 10.21037/gs.2019.11.19.PMID 38137336 ↗Araujo-Castro M, Reincke M, Lamas C. Epidemiology and Management of Hypertension and Diabetes Mellitus in Patients with Mild Autonomous Cortisol Secretion: A Review. Biomedicines. 2023 Nov 22;11(12):3115. doi: 10.3390/biomedicines11123115.PMID 38649778 ↗Prete A, Bancos I. Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches. Nat Rev Endocrinol. 2024 Aug;20(8):460-473. doi: 10.1038/s41574-024-00984-y. Epub 2024 Apr 22.PMID 33017843 ↗Morelli V, Ghielmetti A, Caldiroli A, Grassi S, Siri FM, Caletti E, Mucci F, Aresta C, Passeri E, Pugliese F, Di Giorgio A, Corbetta S, Scillitani A, Arosio M, Buoli M, Chiodini I. Mental Health in Patients With Adrenal Incidentalomas: Is There a Relation With Different Degrees of Cortisol Secretion? J Clin Endocrinol Metab. 2021 Jan 1;106(1):e130-e139. doi: 10.1210/clinem/dgaa695.PMID 33528757 ↗Sojat AS, Dunjic-Kostic B, Marina LV, Ivovic M, Radonjic NV, Kendereski A, Cirkovic A, Tancic-Gajic M, Arizanovic Z, Mihajlovic S, Vujovic S. Depression: another cortisol-related comorbidity in patients with adrenal incidentalomas and (possible) autonomous cortisol secretion. J Endocrinol Invest. 2021 Sep;44(9):1935-1945. doi: 10.1007/s40618-021-01509-4. Epub 2021 Feb 2.PMID 29963828 ↗Reimondo G, Puglisi S, Pia A, Terzolo M. Autonomous hypercortisolism: definition and clinical implications. Minerva Endocrinol. 2019 Mar;44(1):33-42. doi: 10.23736/S0391-1977.18.02884-5. Epub 2018 Jul 2.PMID 34978855 ↗Prete A, Subramanian A, Bancos I, Chortis V, Tsagarakis S, Lang K, Macech M, Delivanis DA, Pupovac ID, Reimondo G, Marina LV, Deutschbein T, Balomenaki M, O'Reilly MW, Gilligan LC, Jenkinson C, Bednarczuk T, Zhang CD, Dusek T, Diamantopoulos A, Asia M, Kondracka A, Li D, Masjkur JR, Quinkler M, Ueland GA, Dennedy MC, Beuschlein F, Tabarin A, Fassnacht M, Ivovic M, Terzolo M, Kastelan D, Young WF Jr, Manolopoulos KN, Ambroziak U, Vassiliadi DA, Taylor AE, Sitch AJ, Nirantharakumar K, Arlt W; ENSAT EURINE-ACT Investigators*; ENSAT EURINE-ACT Investigators. Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study. Ann Intern Med. 2022 Mar;175(3):325-334. doi: 10.7326/M21-1737. Epub 2022 Jan 4.
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