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

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

Working hypothesis: the interactions between the endogenous endocannabinoïds (ECS) - and cortisol, the end product of the Hypothalamo-Pituitary-Adrenal (HPA) axis may play a role in the pathophysiology of Cushing's syndrome.

The investigators speculate that:

• acute or chronic variations in plasma cortisol may induce changes in the activity of the ECS
• that there is a circadian rhythm of the ECS driven by the rythm of plasma cortisol

The study aim to identify the relationship between the ECS and the HPA axis in humans with a main objective to assess if Cushing's syndrome induces changes in the ECS activity.

For this purpose:

1. the investigors will compare plasma levels of ECS between obese controls and patients with Cushing's syndrome
2. the investigors will compare plasma levels of ECS in patients with Cushing's syndrome before and immediately after curative surgery
3. the investigors will compare plasma levels of ECS in patients with hypoadrenalism before and after the intake of substitutive doses of hydrocortisone
4. the investigors will evaluate the plasma levels of ECS during a short synacthen test in healthy subjects.

Inclusion Criteria:

For all patients groups:

• Age ≥ 18,
• Social security.

" Hypercortisolism " group:

• 18 < BMI < 40 kg/m2,
• Cushing's syndrome in front of :
• impaired 1 mg dexamethasone test (08:00 A.M. cortisol > 50 nmol/L)
• qualitative and quantitative disrupted circadian rhythm of cortisol with increased plasma concentrations
• free urinary cortisol upper normal range (90 µg/24H),
• Hypercortisolism that can be treated with surgery (adrenal adenoma treated with adrenalectomy or Cushing disease treated with pituitary surgery).

" Obese " group:

• Obese patients: 30 < BMI < 40 kg/m2,
• Normal HPA axis function:
• 08:00 A.M. cortisol > 250 nmol/L and peak above 550 nmol/L after 1 mg SST,
• Normal 24H free urinary cortisol and dexamethasone test. " Control " group:
• Lean or overweight patients (18 < BMI < 30 kg/m2),
• Non cortisol secreting pituitary or adrenal tumor,
• Patient in whom a biological evaluation of the HPA axis is recommended.

" Hydrocortisone " group:

• Lean or overweight patients (18 < BMI < 30 kg/m2),
• Primary or secondary adrenal insufficiency,
• With a need for hydrocortisone supplementation.

Exclusion Criteria:

• Patients with eating disorders, major depressive disorders or psychiatric disorders other than Cushing's syndrome,
• Cannabis consumption, alcoholism or drug addiction,
• Active smoking,
• cortisone treatment other than hydrocortisone,
• Pregnancy or feeding,
• Surgery for obesity,
• Incapability,
• Pathology that is life-threatening in the short term,
• Any situation that interfere with study or is risked for patient.