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.
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.
Co-enrollment in protocol 19DK0066.
Inability to comply with all study procedures and visits.
Inability of subject to understand or to sign a written informed consent document.
Pregnancy or breastfeeding.
Use of estrogen-containing oral contraceptives or oral estrogen therapy within 6 weeks before inpatient admission, due to possible increases in serum corticosteroid-binding globulin, and thereby total cortisol.
Parallel
Ketoconazole
DrugAntifungal medication that blocks adrenal steroidogenesis, including cortisol production, at higher doses
To assess the circadian rhythm of serum cortisol in participants with MACS compared to that in matched healthy volunteers (HV).
Difference in serum cortisol between MACS and HV at timepoints 1600h, 1800h, 2000h, 2200h, 0000h and 0200h during 24-hour sampling.
To determine the degree of serum cortisol reduction induced by a single dose of 400 mg ketoconazole (KTZ) in participants with MACS.
Difference in serum cortisol after KTZ compared to baseline sampling during the same timepoints the day prior.
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