Hypersecretion; Cortisol, Metabolic Syndrome
Conditions
Brief summary
In obese individuals cortisol production and secretion is increased but the underlying mechanism is not known. Obesity leads to a pathological activation of the innate immune system partly driven by tissue production of IL-1β. Furthermore, IL-1β is also known to stimulate the release of adrenocorticotropin hormone (ACTH). Therefore, the investigators hypothesise that in obese individuals tissue inflammation stimulates ACTH via IL-1β, thereby explaining the observed hypercortisolism.
Interventions
DRUGAnakinra
Anakinra 100mg s.c. x 5
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-80 years * BMI \>30kg/m2 and at least 1 manifestations of the metabolic syndrome (i.e. diabetes/ prediabetes, hypertension, dyslipidemia) * Willingness to use contraceptive measures adequate to prevent becoming pregnant
Exclusion criteria
* Medication with glucocorticosteroids * Known Cushing Syndrome * Pregnancy or breast feeding * Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months * Hematologic disease (leukocyte count \< 1.5x109/l, hemoglobin \<11 g/dl, platelets \<100 x 103/ul) * Kidney disease (creatinine-clearance \< 30ml/min)) * Liver disease (transaminases \>4x upper normal range) * Active carcinoma * History of tuberculosis * Alcohol consumption \>40g/d for men, \>30g/d for women * Known allergy towards anakinra * Subject refusing or unable to give written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Morning cortisol levels | 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test | 14 days | — |
| correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret® | 14 days | — |
| correlation between inflammatory parameters with cortisol levels | 14 days | — |
| impact of anakinra/Kineret® on other pituitary and peripheral hormones, such as: ACTH, TSH, fT4, GH, IGF-1, LH, FSH, testosterone copeptin, IL-6, CRP, leukocyte count and body temperature. | 14 days | impact of anakinra/Kineret® on other pituitary and peripheral hormones such as: ACTH, thyroid-stimulating Hormone (TSH), free thyroxine 4 (fT4), growth Hormone (GH), insulin like growth factor (IGF)-1, luteinizing Hormone (LH), follicle stimulating Hormone (FSH), testosterone copeptin, interleukin (IL)-6, C reactive protein (CRP), leukocyte count and body temperature. |
| comparison of 1mg and 2mg dexamethasone suppression test | 4 weeks | — |
Countries
Switzerland
Outcome results
None listed