Mild Autonomous Cortisol Secretion (MACS)MACSNCT06344143
Detecting Mild Autonomous Cortisol Secretion in Patients With Adrenal Incidentaloma
An observational study of Mild Autonomous Cortisol Secretion (MACS), run by The Cleveland Clinic at 1 site in United States.
Trial summary
The aim of the proposed study is to estimate the incidence of Mild Autonomous Cortisol Secretion (MACS) in patients with Adrenal Incidentaloma (AI) and evaluate the available diagnostic tests to determine the most sensitive and specific combination of tests for assessing MACS from adrenal adenoma for prediction of the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mild Autonomous Cortisol Secretion (MACS)
- What is being tested?
- Various labs and imaging tests
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Nov 2024to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects will be recruited from Endocrinology patients who have previously undergone dexamethasone suppression testing for Adrenal Incidentaloma (AI) or have been diagnosed with AI and have been seen at the Endocrinology and Metabolism institute (EMI). They will be identified from review the laboratory database and clinical records. All subjects with a dexamethasone suppression test <5 micrograms/dL will be invited to participate in the study.
Who may be able to join
- Patients ages 18 years and older.
- Presence of adrenal incidentaloma by cat scan (CT) or magnetic resonance imaging (MRI) examination.
- 1-mg Dexamethasone suppression test cortisol ≤ 5 μg/dL with adequate dexamethasone level.
Who cannot join
- 1-mg Dexamethasone suppression test cortisol > 5 μg/dL with adequate dexamethasone level. Patients who fail to suppress below this level will be considered to have Cushing's syndrome and will be referred for appropriate treatment.
- Current or recent (3 months) history of use of glucocorticoid medication (including joint injections of steroids).
- History of uncontrolled hypertension or history of hypertension with more than 2 medications.
- History of uncontrolled type 2 Diabetes Mellitus or history of diabetes mellitus with A1c>7.5.
- Known History of osteoporosis
- Documented Clinical Cushing's disease.
Show all 14Show fewer
- Clinical suspicion of adrenal carcinoma.
- History of alcohol abuse/dependence.
- History of cirrhosis of liver.
- History of hepatitis B or C infection regardless of treatment.
- History of type 1 diabetes.
- History of hemochromatosis.
- History of autoimmune hepatitis.
- History of Wilson's disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Maya Boyd, 216.444.4919, boyda5@ccf.org
jenkink@ccf.org Jenkins, 216-445-4791, jenkink@ccf.org
About this study
The aim of the proposed study is to estimate the incidence of Mild Autonomous Cortisol Secretion (MACS) in patients with Adrenal Incidentaloma (AI) and evaluate the available diagnostic tests to determine the most sensitive and specific combination of tests for assessing MACS from adrenal adenoma for prediction of the phenotype associated with cortisol excess. As well as following the patients for 4 years and see if anything changes.
Read the detailed description
Mild Autonomous cortisol secretion (MACS) is defined as the hypersecretion of cortisol by the adrenal glands, independent of Adrenocorticotropic Hormone (ACTH) regulation. MACS can be a challenging diagnosis for clinicians to make. It is commonly associated with adrenal incidentalomas (AI), the incidental finding of adrenal gland masses on cross-sectional imaging. There are a variety of adverse clinical conditions associated with MACS, including central obesity, hypertension, impaired fasting glucose due to insulin resistance, and dyslipidemia, which together comprise the "metabolic syndrome," as well as type 2 diabetes mellitus, cardiovascular disease, osteoporosis with vertebral fractures, and early mortality. Androulakis et al. concluded that patients with AI, even without hypertension, diabetes, and/or dyslipidemia, may still have adverse cardiovascular outcomes, possibly due to increased insulin resistance and endothelial dysfunction linked to subtle cortisol excess. There is also a reported association of non-alcoholic fatty liver disease (NAFLD), an increasingly significant cause of morbidity and mortality, with the metabolic syndrome and diabetes, as well as hypercortisolism. However, the link between MACS and NAFLD has not been well delineated, nor has the effect of treatment with MACS on NAFLD been explored.
Given the findings cited above, there may be benefit in treating patients with AI and MACS with medical therapy. Therefore, identifying those individuals who have the metabolic syndrome or its components, bone disease, NAFLD, or increased cardiovascular risk related to excess cortisol secretion is essential but difficult.
- Being tested
- Various labs and imaging tests
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Various labs and imaging testsDiagnostic test
Dexamethasone Suppression Test, Adrenocorticotropic Hormone (ACTH), Salivary Cortisol Levels, Vasopressin Stimulation test, Fasting Glucose, Fasting Insulin, Complete Metabolic Panel (CMP), Gamma-glutamyl transferase (GGT), Sex Hormone Binding Globulin, Cat scan of abdomen/Pelvis, Whole body dual energy x-ray absorptiometry (DXA) scan, Ultrasound Fibroscan Transient Elastography
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate best diagnostic test(s)
To evaluate and determine the most sensitive and specific combination of tests for assessing mild autonomous cortisol secreting (MACS) from adrenal adenoma for prediction of the phenotype associated with cortisol excess. Study team will measure cortisol in serum, cortisol in saliva, cortisol in urine, vasopressin stimulation test, 1 mg dexamethasone stimulation test (DST) and a 2 mg DST, Adrenocorticotropic Hormone test (ACTH) and (dehydroepiandrosterone sulfate test) DHEAS. With this, a diagnosis of MACS can be determined. To determine the sensitivity of each the area under the curve (AUC) will be compared with the standard test which is 1 mg DST.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start20 Nov 2024
- Primary completion1 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Autonomous Cortisol Secretion (MACS)Studies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- RECORDATI GROUP
- Responsible party
- Sponsor
- Investigators
- Ricardo Correa, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06344143
- Sponsor's protocol ID
- 24-324
- Acronym
- MACS
- Status last verified
- Jan 2026
- First submitted
- 27 Mar 2024
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detecting Mild Autonomous Cortisol Secretion in Patients With Adrenal Incidentaloma
- ClinicalTrials.gov ID
- NCT06344143
- Acronym / sponsor ID
- MACS / 24-324
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- RECORDATI GROUP
- Study start
- 20 Nov 2024 (actual)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 3 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the proposed study is to estimate the incidence of Mild Autonomous Cortisol Secretion (MACS) in patients with Adrenal Incidentaloma (AI) and evaluate the available diagnostic tests to determine the most sensitive and specific combination of tests for assessing MACS from adrenal adenoma for prediction of the phenotype associated with cortisol excess. As well as following the patients for 4 years and see if anything changes.
Detailed description
Mild Autonomous cortisol secretion (MACS) is defined as the hypersecretion of cortisol by the adrenal glands, independent of Adrenocorticotropic Hormone (ACTH) regulation. MACS can be a challenging diagnosis for clinicians to make. It is commonly associated with adrenal incidentalomas (AI), the incidental finding of adrenal gland masses on cross-sectional imaging. There are a variety of adverse clinical conditions associated with MACS, including central obesity, hypertension, impaired fasting glucose due to insulin resistance, and dyslipidemia, which together comprise the "metabolic syndrome," as well as type 2 diabetes mellitus, cardiovascular disease, osteoporosis with vertebral fractures, and early mortality. Androulakis et al. concluded that patients with AI, even without hypertension, diabetes, and/or dyslipidemia, may still have adverse cardiovascular outcomes, possibly due to increased insulin resistance and endothelial dysfunction linked to subtle cortisol excess. There is also a reported association of non-alcoholic fatty liver disease (NAFLD), an increasingly significant cause of morbidity and mortality, with the metabolic syndrome and diabetes, as well as hypercortisolism. However, the link between MACS and NAFLD has not been well delineated, nor has the effect of treatment with MACS on NAFLD been explored.
Given the findings cited above, there may be benefit in treating patients with AI and MACS with medical therapy. Therefore, identifying those individuals who have the metabolic syndrome or its components, bone disease, NAFLD, or increased cardiovascular risk related to excess cortisol secretion is essential but difficult.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be recruited from Endocrinology patients who have previously undergone dexamethasone suppression testing for Adrenal Incidentaloma (AI) or have been diagnosed with AI and have been seen at the Endocrinology and Metabolism institute (EMI). They will be identified from review the laboratory database and clinical records. All subjects with a dexamethasone suppression test <5 micrograms/dL will be invited to participate in the study.
Key inclusion criteria (3 listed)
- Patients ages 18 years and older.
- Presence of adrenal incidentaloma by cat scan (CT) or magnetic resonance imaging (MRI) examination.
- 1-mg Dexamethasone suppression test cortisol ≤ 5 μg/dL with adequate dexamethasone level.
Key exclusion criteria (14 listed)
- 1-mg Dexamethasone suppression test cortisol > 5 μg/dL with adequate dexamethasone level. Patients who fail to suppress below this level will be considered to have Cushing's syndrome and will be referred for appropriate treatment.
- Current or recent (3 months) history of use of glucocorticoid medication (including joint injections of steroids).
- History of uncontrolled hypertension or history of hypertension with more than 2 medications.
- History of uncontrolled type 2 Diabetes Mellitus or history of diabetes mellitus with A1c>7.5.
- Known History of osteoporosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Various labs and imaging testsDexamethasone Suppression Test, Adrenocorticotropic Hormone (ACTH), Salivary Cortisol Levels, Vasopressin Stimulation test, Fasting Glucose, Fasting Insulin, Complete Metabolic Panel (CMP), Gamma-glutamyl transferase (GGT), Sex Hormone Binding Globulin, Cat scan of abdomen/Pelvis, Whole body dual energy x-ray absorptiometry (DXA) scan, Ultrasound Fibroscan Transient Elastography | Diagnostic test | – |
Primary outcome
Evaluate best diagnostic test(s)
Time frame: 5 years
To evaluate and determine the most sensitive and specific combination of tests for assessing mild autonomous cortisol secreting (MACS) from adrenal adenoma for prediction of the phenotype associated with cortisol excess. Study team will measure cortisol in serum, cortisol in saliva, cortisol in urine, vasopressin stimulation test, 1 mg dexamethasone stimulation test (DST) and a 2 mg DST, Adrenocorticotropic Hormone test (ACTH) and (dehydroepiandrosterone sulfate test) DHEAS. With this, a diagnosis of MACS can be determined. To determine the sensitivity of each the area under the curve (AUC) will be compared with the standard test which is 1 mg DST.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Mild Autonomous Cortisol Secretion (MACS)
Not yet recruitingPhase 2
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Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
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Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)
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Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ricardo Correa, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mild Autonomous Cortisol Secretion (MACS), run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kimberly Jenkins (216-445-4791, jenkink@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate best diagnostic test(s) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.