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:
    • 1 mg post-dexamethasone cortisol > 1.8 mcg/d;  or
    • 8 mg post-dexamethasone cortisol > 1 mcg/dL;
  • Historical dexamethasone suppression test results can be used if performed within 6 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/m^2);
  • Dysglycemia;
  • Dyslipidemia;
  • Hypertension;
  • Osteopenia;
  • Osteoporosis;
  • Fragility fractures.
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• For females of reproductive potential: use of highly effective contraception initiated prior to baseline visit and for 1 month after completing metyrapone study.
• 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 6 months after the last dose of study treatment.
• Stable timing for bedtime for at least one week prior to on-site study visits

Exclusion Criteria:

• Planned alternative therapy for MACS within 6 months after joining the study.
• 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.
• 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 metyrapone.
• 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/14/23. Questions regarding updates should be directed to the study team contact.