Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

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.

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.