Ketoconazole Effects on Cortisol Circadian Rhythm in Mild Autonomous Cortisol Secretion: A Pilot Study
Background: Cortisol is a hormone in the blood. Cortisol levels normally go down at night and up in the morning. Mild autonomous cortisol secretion (MACS) is a disease in which the body makes too much cortisol. MACS can cause high blood pressure, diabetes, and/or weight gain. Researchers think these problems may be caused by higher cortisol levels at night.
Objective: To compare daily cortisol levels in people with MACS with those in healthy people. Also, to test a drug (ketoconazole) that may help lower cortisol levels in people with MACS.
Eligibility: People aged 18 years and older with MACS. Healthy volunteers are also needed.
Design: Participants with MACS will have a 2-night stay in the hospital. Day 1: A thin tube called a catheter will be inserted into a vein in the arm. Blood will be collected through the catheter every 2 hours starting at 8 PM. Participants will begin a 24-hour urine collection. Saliva will be collected every 6 hours for 24 hours. Day 2: Participants will take 2 tablets of the study drug ketoconazole with their evening meal. Blood will be collected via the catheter at regular intervals throughout the night. Day 3: Participants will leave the hospital in the morning. Healthy volunteers will be screened with a physical exam and blood tests. They will be tested to make sure they do not have MACS. To do this, they will take a drug (dexamethasone) at 11 PM on a day they choose; then they will return the next morning for a blood test. Healthy volunteers will have a 1-night stay in the hospital. They will have blood, urine, and saliva collected for 24 hours.
∙ To be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged 18 years or older.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Agreement to adhere to Lifestyle Considerations throughout the study.
∙ A. Subjects with Mild Autonomous Cortisol Secretion (MACS):
• Co-enrollment in protocol 19DK0066.
• Abnormal low-dose overnight dexamethasone suppression test (morning serum cortisol \>1.8 mcg/dL following 1 mg oral dexamethasone between 2300-0000h the evening prior)
• One or more \>=1 cm adrenal nodule(s) on one or both adrenal glands on CT or MRI
• One normal 24-hour urine free cortisol value (per the reference range of the assay used).
• One morning plasma ACTH value \<10 pg/mL.
∙ B. Healthy volunteers:
• In good general health as evidenced by medical history and physical examination; and in a stable state of health without ongoing acute/temporary illness per the clinical judgment of the investigator.
• Normal low-dose overnight dexamethasone suppression test (morning serum cortisol \<=1.8 mcg/dL following 1 mg oral dexamethasone between 2300-0000h the evening prior)
• Matching a participant with MACS who has completed testing in regard to:
‣ Age: Birth year within 5 years of that of the participant with MACS.
⁃ Sex
⁃ BMI (kg/m2) category: \<18.5 (underweight); 18.5-24.9 (normal weight); 25-29.9 (overweight); 30-34.9 (obesity class 1); 35-39.9 (obesity class 2); \>=40 (obesity class 3).
⁃ For women: menopausal status as judged by absence of menses for one year and FSH\>15 mIU/mL.