Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

* Age \>18 years old with confirmed mild autonomous cortisol secretion (MACS) Cushing's syndrome, defined by:

  * At least two abnormal 1 mg Dexamethasone suppression tests (Cortisol \> 1.8 ug/dL at 8-9 am after taking 1 mg dexamethasone at 11 pm) with appropriate dexamethasone level for the assay (last level within 3 months before enrollment).
  * Having at least two early morning fasting ACTH \<15 pg/mL (last level within 3 months before enrollment)
* Presence of at least one of the following comorbidities:

  * The presence of prediabetes or Type 2 diabetes mellitus (T2DM): fasting plasma glucose ≥100 mg/dL and/or 2-hour Oral Glucose Tolerance Test (OGTT) glucose ≥140 mg/dL, or HbA1c ≥5.7%
  * Systolic hypertension is defined as a mean Systolic Blood Pressure (SBP) ≥130 mmHg after 5 min rest in a seated position (mean of 3 blood pressure measurements 5 minutes apart) irrespective of the number of anti-hypertensive medications.
  * BMI \>30 kg/m2
* The presence of an adrenal adenoma or hyperplasia, as determined by CT or MRI studies
* Negative urine pregnancy test at Baseline (urine) for women of childbearing potential

Exclusion criteria:

* Has severe, uncontrolled hypertension (mean SBP \>170 mm Hg or mean Diastolic Blood Pressure (DBP) \>110 mm Hg at Screening)
* Has poorly controlled DM (HbA1c \>11% at Screening).
* Has abnormal liver test results (total bilirubin \>1.5×ULN or elevated alanine aminotransferase or aspartate aminotransferase \>3×ULN at Baseline).
* Has severe renal insufficiency (glomerular filtration rate ≤29 mL/min at Baseline).
* Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
* Has prolonged QT interval corrected for heart rate using Fridericia's equation (QTcF) (\>450 ms for men and \>470 ms for women) with a normal QRS interval (\<120 ms) or QTcF interval \>500 ms with wide QRS interval (≥120 ms).
* Has persistent atrial fibrillation.
* Has uncorrected hypokalemia.
* Has used or plans to use any treatments for MACS within 12 weeks before Screening and throughout the study, including metyrapone, mifepristone, ketoconazole, fluconazole, or any investigational drug for the treatment of hypercortisolism.
* Has adrenocortical carcinoma, or the adrenal images are suspicious for an underlying malignancy.
* Has autonomous co-secretion of aldosterone.
* Has plans for adrenalectomy or nodulectomy during the study.
* Pregnancy, lactating, or intends to become pregnant in the next 2 years.
* Female patients of childbearing potential who cannot use a highly effective method of contraception, including all women \<50 years old, women whose surgical sterilization was performed \<6 months ago.