Mild Autonomous Cortisol Secretion (MACS)
Conditions
Keywords
MACS, Mild Autonomous Cortisol Secretion, Adrenal Adenoma, Osilodrostat, Isturisa, Body Composition, Metabolic Outcomes, Subclinical Cushing Syndrome, Adrenal hyperplasia, Carotid intima thickness, Bone mineral density, Hypertension, Glycemic control
Brief summary
To characterize the impact of Isturisa on clinical features and comorbidities associated with MACS. The investigators hypothesize that patients treated with Isturisa will exhibit significantly better metabolic indicators (such as fasting glucose, HbA1c, and lipid profile), blood pressure, weight, body composition and bone mineral density than at Baseline. The investigators also assess the effect of Isturisa on quality of life and psychological symptoms in patients with MACS. The investigators hypothesize that treatment with Isturisa will lead to significant improvements in quality-of-life scores and reductions in depression scores compared to Baseline.
Detailed description
Mild autonomous cortisol secretion (MACS) is diagnosed in up to 48% of patients with incidentally discovered adrenal tumors or hyperplasia. Based on the finding of adrenal masses in 5% of adults undergoing cross-sectional imaging, the overall prevalence of MACS is about 1-2%. MACS is characterized by autonomous cortisol secretion without the overt symptoms of Cushing syndrome. It is usually associated with low ACTH and DHEAS levels as an indicator of autonomous cortisol secretion. The European Society of Endocrinology-European Network for the Study of Adrenal Tumors (ESE-ENSAT) and the American Association of Clinical Endocrinology (AACE) recommend a cortisol \>1.8 μg/dL after 1 mg-DST to define MACS. Several metabolic abnormalities are associated with MACS, including increased cardiovascular disease, mood alteration, hypertension, osteoporosis, hyperglycemia, obesity, weight gain, and lipid abnormalities. Additionally, increased mortality has been reported in MACS patients. Given these complications and increased mortality, there is a need for effective management and treatment options for MACS. This research aims to evaluate the efficacy and safety of Isturisa in patients with MACS to address the current gap in treatment strategies. By assessing how effectively Isturisa improves cardiometabolic disorders and monitoring its safety profile, the research will seek to provide a clearer understanding of its role as a treatment option in MACS patients who are not a surgical candidate or do not want to pursue surgery. This evaluation is crucial for developing more effective treatment options and improving management strategies for MACS, ultimately contributing to better patient management.
Interventions
DRUGOsilodrostat (Isturisa)
The intervention aims to evaluate the impact of osilodrostat on cardiometabolic outcomes, bone mineral density, body composition, adrenal tumor size or hyperplasia, and biochemical markers of cortisol excess.
Sponsors
Johns Hopkins University
Recordati Rare Diseases Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. No parties are masked
Intervention model description
This is a single-arm, interventional study in which all enrolled participants with MACS will receive Osilodrostat (Isturisa). The patients will be evaluated for the impact of Isturisa on clinical features and comorbidities associated with MACS.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged ≥18 years. * Diagnosis of mild autonomous cortisol secretion (MACS) defined by: * Serum cortisol \>1.8 µg/dL after 1 mg overnight dexamethasone suppression test (DST). * Presence of adrenal adenoma confirmed by imaging (CT or MRI). * Ability to provide informed consent. * Willingness to undergo study procedures including DEXA scan and laboratory assessments.
Exclusion criteria
* Known diagnosis of Cushing's syndrome or overt hypercortisolism. * Current or recent (within 3 months) treatment with glucocorticoids or medications affecting cortisol production (e.g., ketoconazole, metyrapone). * Severe hepatic impairment or renal failure. * Pregnancy or breastfeeding. * Known allergy or contraindication to osilodrostat (Isturisa). * Participation in another interventional clinical trial within the last 30 days. * Any medical or psychiatric condition that, in the investigator's judgment, may interfere with study participation or safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting glucose, HbA1c | Baseline, and then every 3 months up to 2 years | glycemic control: fasting glucose, HbA1c |
| Change in bone mineral density (g/cm²) | Baseline, 1 year, and 2 years | Bone mineral density (g/cm²) measured by DEXA scan. |
| Change in body weight (kg) from baseline during Isturisa treatment | Baseline and every 3 months up to 2 years | Change in body weight will be measured at baseline and every follow-up visit (approximately every 3 months) throughout the 2-year treatment period with Isturisa. |
| Change in lipid profile from baseline during Isturisa treatment | Baseline and every 3 months up to 2 years | Serum lipid profile (LDL-C, HDL-C, total cholesterol, triglycerides) will be assessed at baseline and every follow-up visit (approximately every 3 months) during the 2-year treatment period. |
| Change in body composition (kg) | baseline, 1 year and 2 years | Body composition including lean mass and fat mass (kg) measured by DEXA scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life as assessed by Short Form -36 (SF-36) | Baseline and every 3 months up to 2 years | Assessment of changes in quality of life using the SF-36 Health Survey. The SF-36 consists of 36 items measuring 8 health domains, with total scores ranging from 0 to 100, where higher scores indicate better quality of life. |
| Change in carotid intima-media thickness (CIMT) | Baseline, 1 year, and 2 years | Carotid intima-media thickness (milimeters) will be measured using carotid ultrasound to evaluate vascular changes associated with mild autonomous cortisol secretion. CIMT will be assessed at baseline and at follow-up imaging performed approximately every 12 months during the 2-year treatment period. |
| Change in adrenal adenoma/hyperplasia size (mm) | Baseline, 1 year, and 2 years | Adenoma maximal diameter (mm) measured on non-contrast CT at each imaging time point. |
| Change in Depression Scores as assessed by the Beck Depression Inventory-II | Baseline and every 3 months up to 2 years | Assessment of changes in depressive symptoms using the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item validated questionnaire with total scores ranging from 0 to 63, where higher scores indicate more severe depressive symptoms. |
Countries
United States
Contacts
CONTACTPooneh Jabbaripour Sarmadian, MD
CONTACTTony Keyes
PRINCIPAL_INVESTIGATORAmir Hamrahian, MD
Johns Hopkins University
Outcome results
None listed