Detecting Mild Autonomous Cortisol Secretion in Patients With Adrenal Incidentaloma (MACS)

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.

Study Overview

• Status: Recruiting
• Conditions: Mild Autonomous Cortisol Secretion (MACS)
• Intervention / Treatment: Diagnostic test: Various labs and imaging tests

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 Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Kimberly Jenkins; Phone Number: 216-445-4791; Email: jenkink@ccf.org
• Study Contact Backup: Name: Andrea Parianos; Phone Number: 216 210-7832; Email: debsa@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic Foundation
      • Contact: jenkink@ccf.org Jenkins; Phone Number: 216-445-4791; Email: jenkink@ccf.org
      • Contact: Maya Boyd; Phone Number: 216.444.4919; Email: boyda5@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

1. Patients ages 18 years and older.
2. Presence of adrenal incidentaloma by cat scan (CT) or magnetic resonance imaging (MRI) examination.
3. 1-mg Dexamethasone suppression test cortisol ≤ 5 μg/dL with adequate dexamethasone level.

Exclusion Criteria:

1. 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.
2. Current or recent (3 months) history of use of glucocorticoid medication (including joint injections of steroids).
3. History of uncontrolled hypertension or history of hypertension with more than 2 medications.
4. History of uncontrolled type 2 Diabetes Mellitus or history of diabetes mellitus with A1c>7.5.
5. Known History of osteoporosis
6. Documented Clinical Cushing's disease.
7. Clinical suspicion of adrenal carcinoma.
8. History of alcohol abuse/dependence.
9. History of cirrhosis of liver.
10. History of hepatitis B or C infection regardless of treatment.
11. History of type 1 diabetes.
12. History of hemochromatosis.
13. History of autoimmune hepatitis.
14. History of Wilson's disease.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 years

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: RECORDATI GROUP
• Investigators: Principal Investigator: Ricardo Correa, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Adrenocortical Adenoma
• Other Study ID Numbers: 24-324

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No