Metyrapone for Mild Autonomous Cortisol Secretion (MACS)

Who can take part

• Provide written informed consent
• Stated willingness to comply with all study procedures and availability for the duration of the study
• 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) and 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/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

Who cannot take part

• 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
• Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
• 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
• 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
• Known allergic reactions to metyrapone
• Use of injectable glucocorticoid within the last 6 weeks
• Pregnancy or lactation