Clinical trial: Preoperative Bexarotene Treatment for Cushing's Disease (NCT00845351)

Eligibility criteria:
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:

               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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 65 Years

Patient description (medical language): A 47-year-old man comes to the office due to weight gain and fatigue.  He is not able to lift heavy objects or climb stairs. Family history is positive for DM type 2 and HTN in his father.  Blood pressure is 165/90 mm Hg and pulse is 85/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 138 mg/dL and 24-hour urinary cortisol is twice the upper normal limit.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal. This patient's findings are consistent with endogenous Cushing Syndrome.

Patient description (patient's own words): I'm a 47-year-old man. I went to the clinic because I had been gaining weight and had increased fatigue over the past few weeks. I was not able to lift heavy objects or even climb the stairs. My dad was diagnosed with type 2 diabetes and high blood pressure. During the exam, they took my blood pressure, which was 165/90 mm Hg, and my pulse was 85/min. They found out that I have weaknesses in both of my arms and legs. I also did a blood test on an empty stomach, and I had a glucose level of 138 mg/dL, and twice the upper normal limit of cortisol. I had high-normal levels of ACTH. The doctor said I suffer from endogenous Cushing Syndrome.

Does the patient match the trial criteria? 1