Ketoconazole Effects on Cortisol Circadian Rhythm in Mild Autonomous Cortisol Secretion: A Pilot Study
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Summary
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.
Description
Study Description: This study will compare the circadian rhythm of serum cortisol in subjects with Mild Autonomous Cortisol Secretion (MACS) and healthy volunteers (HVs). At the end of 24-hour baseline sampling, participants with MACS will receive a single dose of ketoconazole (KTZ) and undergo continued serial sampling to assess its effect on cortisol production. We hypothesize that subjects with MACS have decreased diurnal variability of serum cortisol, leading to relative excess in the evening and early overnight hours. We also hypothesize that a single dose of KTZ lowers cortisol enough t…