Clinical Trials

Inclusion Criteria:

* Provide written informed consent
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Age ≥ 18 years
* Diagnosed with MACS

* At least 2 abnormal post-dexamethasone cortisol results:

i. 1 mg post-dexamethasone cortisol \>1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol \>1 mcg/dL
* Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
* Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
* At least one of the following comorbidities:

* Obesity (BMI\>30 kg/m2)
* Dysglycemia
* Dyslipidemia
* Hypertension
* Osteopenia
* Osteoporosis
* Fragility fractures
* Ability to take oral medication and be willing to adhere to the study intervention regimen
* For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤ 5% per year during the treatment period and for 1 month after the last dose of study treatment.

Exclusion Criteria:

* Planned alternative therapy for MACS during the study period
* Current use of oral exogenous glucocorticoid therapy
* Current use of opioid therapy \>20 MME/day
* Planned use of oral exogenous glucocorticoid therapy
* Planned use of opioid therapy \>20 MME/day
* Use of injectable glucocorticoid within the last 6 weeks or anticipated glucocorticoid use during the study period.
* Hypokalemia of hypomagnesemia at baseline visit
* Prolonged QTc on baseline ECG
* Concomitant therapy with medications likely to lead to drug-drug interactions (based on PI review).
* Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
* Uncontrolled intercurrent illness including, but not limited to:

* Ongoing or active infection
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements
* Pregnancy or lactation
* Known allergic reactions to osilodrostat
* Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.
* Treatment with another investigational drug or other intervention within lower than specific therapy washout period