BexarotenePreoperative Bexarotene Treatment for Cushing's Disease

Inclusion Criteria:

• Age 18-65
• Clinical and biochemical diagnosis of Cushing's disease as established by clinical history, physical exam, and definitive biochemical testing:

1. Persistent hypercortisolemia established by 24 hour urine free cortisol measurements
2. Confirmation of pituitary-dependent hypercortisolemia 1. ACTH levels normal or elevated, and if clinically necessary, one of the following:

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1. Suppression of 24 hour urine free cortisol with either the 48-hour dexamethasone suppression test, or suppression of serum cortisol after an overnight high-dose (8 mg) dexamethasone suppression test -OR-
2. Inferior Petrosal Sinus Sampling (IPSS) study

• Pituitary MRI performed within three months of enrollment
• Health status deemed appropriate for transsphenoidal surgery by the neurosurgical preoperative evaluation at the University of Virginia Pituitary Clinic

Exclusion Criteria:

• Age less than 18 or greater than 65
• Pregnant or nursing mothers
• Previous surgical, medical, or radiation therapy involving the pituitary fossa
• History of malignancy, solid or hematogenous
• History of intracranial disease, injury or intracranial surgical procedure
• Renal impairment with a GFR estimated at < 60 mL/min/1.73 m2
• History of liver disease, or baseline liver transaminase levels >50% above the upper limit of normal
• Fasting Triglycerides > 200 mg/dL
• History of pancreatitis
• Pituitary macroadenoma (> 1 cm) as measured by MRI performed within 3 months of enrollment
• Previous treatment for Cushing's disease including surgery, radiation, or medical therapy:

1. Ketoconazole
2. Metyrapone
3. Aminoglutethimide
4. Mitotane

• Oral or systemic glucocorticoid use in the last six months
• Intraarticular injection of glucocorticoids in the last year
• Current use of Ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, or other inhibitors of cytochrome P450 3A4
• Any disability or cognitive, educational, or language barriers which would inhibit the subject's ability to adequately understand the verbal and written material in the consent process despite the use of standard language translation services available through our clinic