Obesity, Addison's Disease
Conditions
Brief summary
Replacing glucocorticoid in a dose dependent manner (including doses within the physiological range) to subjects with adrenal insufficiency will increase visceral fat accumulation independently of total fat mass.
Detailed description
To measure total fat mass by DEXA scan, central (visceral) fat accumulation, insulin sensitivity by FSIVGTT, lipid levels, and adipocyte gene expression in subjects with AI receiving increasing doses of hydrocortisone replacement (15 mg, 25 mg, and 40 mg per day in split doses) for 4-months at a time during ad-lib feeding.
Interventions
DRUGHydrocortisone
Subjects will receive in random order daily (split) dosing of hydrocortisone: a low dose of 15 mg (10 in AM, 5 in PM); a medium dose of 25 mg (15 in AM, 10 in PM) and high dose of 40 mg (30 in AM, 10 in PM) for 4 months.
DIETARY_SUPPLEMENTIsocaloric Diet
Subjects will eat an isocaloric diet for 4 weeks while taking hydrocortisone
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with complete adrenal failure as defined as spontaneous serum cortisol of levels less than 5 g/dl after 12 hours without glucocorticoid replacement and peak serum cortisol of \< 5 g/dl 60 minutes after a 250 g ACTH stimulation test. * Subjects who are at their usual weight (weight stable for at least 1 year) * Subjects on stable replacement doses of any required hormone such as thyroid, sex hormones, mineralocorticoid replacement, growth hormone, and hydrocortisone for at least 6 months, and 4) have a normal body weight (BMI 19-27 kg/m2).
Exclusion criteria
* Possible confounders on body weight and insulin resistance * Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth. * Subjects who exercise \> 30 minutes/day, 3 times a week. * Smokers. * Heavy alcohol drinkers (\> 2 drinks/ day). * Subjects with medical diagnosis including diabetes, heart disease, and cancer. * Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Amounts of intra-abdominal fat and total fat at the end of the treatment period for each cortisol dose. | After 4 months on each dose |
Secondary
| Measure | Time frame |
|---|---|
| Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy | After 4-months on each dose |
Countries
United States
Outcome results
None listed