Subjects with BMI between 30 - 40 kg/m2 and no alteration of corticotrope axis.

Subject with BMI between 18 - 40 kg/m2 and presenting a hypercortisolism defined by HAS (Haute Autorité de Santé).

Subject with BMI between 18 - 30 kg/m2 and with adrenal or corticotrope failure

Subject with BMI between 18 - 30 kg/m2 and with a pituitary or adrenal tumor without effect on corticotrope axis.

Cushing's Syndrome

Obese

Hypercortisolism

Hydrocortisone

Control

Service d'Endocrinologie, Hopital Haut-Leveque

In Vivo Study of Interactions Between the Endocannabinoid System and the Corticotropic Axis in Man

The primary outcome will be assessed by a measurement of plasma concentration of 2-AG during the circadian rhythm of ACTH/cortisol.

The secondary outcome wille be assessed by a measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol.

Measurement of plasma concentration of AEA, OEA and PEA on 07:30 A.M. ± 1 hour (fasting), 08:00 A.M. ± 1 hour (fasting), 09:00 A.M. ± 1 hour, 10:00 A.M. ± 1 hour, 04:00 P.M. ± 1 hour

Measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol

University Hospital, Bordeaux

2 times a day 1 capsule for 4 weeks before gastric bypass surgery

Morbid Obesity

Omega-3 fatty acid capsules

A low calorie diet of 600 kcal/day during 2 weeks, using Modifast or an adjusted normal diet.

Low calorie diet

Rode Kruis Ziekenhuis

Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function

liver volume of the left hepatic lobe measured by MRI

Measurement of erythrocyte deformability and aggregation with LORRCA (laser-assisted optical rotational red cell analyzer)

IL-6, IL-10, TNF-alpha and C-reactive protein

Surgeons fill out a questionnaire after the gastric bypass surgery

Alexander P.J. Houdijk

Medical Center Alkmaar

Near-physiologic doses of Hydrocortisone are being given to subjects. The first day between 09.00 and 12.00 0,024 mg Hydrocortisone/kg per hour. The first day between 12.00 and 20.00 0,012 mg Hydrocortisone/kg per hour. The first day between 20.00 and 24.00 0,008 mg Hydrocortisone/kg per hour. The second day between 00.00 and 11.00 0,030 mg Hydrocortisone/kg per hour. Hydrocortisone infusion: 0,4 ml Solu Cortef 100 mg (50 mg/ml) added in 999,6 ml sodium chloride 0,9% solution (1 mg Solu Cortef/ 50 ml total solution volume).

The same volume of sodium chloride 0,9% as in the other arm where Hydrocortisone is given in saline 0,9% solution. The given volume of sodium chloride will variate chronically as in Hydrocortisone arm.

Addison Disease

Placebo

Sahlgrenska University Hospital

Biomarker(s) for Glucocorticoids

Protein/Metabolite Biomarker(s) for Glucocorticoid Action; an Experimental Trial in Patients With Adrenal Insufficiency

Using mass spectrometry, protein profile changes in blood, urine and adipose tissue are going to be identified between four points of time during two states: morning and midnight during near physiological GC exposure (sampling 1 and 2), morning and midnight during GC starvation (sampling 3 and 4). Quantitative measurements of all proteins will be used in the bioinformatic analysis. The bioinformatics strategic consists of a stepwise approach based on random forest analysis. Key features in the analysis include finding candidate markers that are increased during normal GC exposure (sampling 1 and 2), reduced during GC starvation (sampling 3 and 4) and exclusion of factors with high variability within normal subjects. Putative biomarkers will go through two levels of internal cross-validation. The investigators would like that this part of the project is not going to be public.

Using mass spectrometry, metabolite profile changes in blood, urine and adipose tissue are going to be identified between four points of time during two states: morning and midnight during near physiological GC exposure (sampling 1 and 2), morning and midnight during GC starvation (sampling 3 and 4). Quantitative measurements of all metabolites will be used in the bioinformatic analysis. The bioinformatics strategic consists of a stepwise approach based on random forest analysis. Key features in the analysis include finding candidate markers that are increased during normal GC exposure (sampling 1 and 2), reduced during GC starvation (sampling 3 and 4) and exclusion of factors with high variability within normal subjects. Putative biomarkers will go through two levels of internal cross-validation. The investigators would like that this part of the project is not going to be public.

Using array based transcriptomics (both mRNA & miRNA), mRNA/miRNA profile changes in blood, urine and adipose tissue are going to be identified between four points of time during two states: morning and midnight during near physiological GC exposure (sampling 1 and 2), morning and midnight during GC starvation (sampling 3 and 4). Quantitative measurements of all mRNA/miRNA´s will be used in the bioinformatic analysis. The bioinformatics strategic consists of a stepwise approach based on random forest analysis. Key features in the analysis include finding candidate markers that are increased during normal GC exposure (sampling 1 and 2), reduced during GC starvation (sampling 3 and 4) and exclusion of factors with high variability within normal subjects. Putative biomarkers will go through two levels of internal cross-validation. The investigators would like that this part of the project is not going to be public.

adrenal insufficiency/obésité

In Vivo Study of Interactions Between the Endocannabinoid System and the Corticotropic Axis in Man

Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function

Biomarker(s) for Glucocorticoids

6-Methyl-Prednisolone for Multiple Organ Dysfunction Syndrome

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