Metyrapone for Mild Autonomous Cortisol Secretion (MACS)

Eligibility Criteria

• * 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
• * 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.