Trial Information

Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population

Cushing's syndrome is a rare disease resulting from chronic exposure to glucocorticoids
(endogenous or iatrogenic) with abnormal fat distribution (lipodystrophy). Glucocorticoids
regulate the functions of adipose tissue (AT) targeting adipocyte differentiation as well as
anabolic, catabolic and secretory pathways of the adipocyte. However, the mechanisms by
which glucocorticoids differentially disrupt the development or metabolism of AT between
deep and superficial deposits remain unknown. Among the main effectors of the glucocorticoid
signaling pathway, 11 beta-hydroxysteroid deshydrogenase (11beta-HSD1) , that regenerate
cortisol from cortisone, is likely a key step in the biological effect of glucocorticoids
in AT. Identifying these mechanisms of action of glucocorticoids on different fat depots
requires the comparison with fatty deposits derived from two types of control populations:
1/ normal weight individuals without inflammatory or metabolic disorder (controls1);
2/individuals obese matched for the level of insulin resistance (controls2).

Hypothesis: Excess glucocorticoids cause abnormal fat distribution via a direct effect on
the various deposits of AT, leading secondarily to insulin resistance.

Primary endpoint: To compare gene expression of glucocorticoid signaling between the
visceral AT (VAT) of Cushing patients with that of controls1 (matched for age and sex).

Secondary endpoints:

1. For patients with Cushing and controls1, to compare their respective subcutaneous AT
(SCAT) and VAT for:

- The expression of genes involved in differentiation and inflammation of the AT,

- Morphological aspects: adipocyte size, fibrosis, inflammation,
immunohistochemistry.

2. Same parameters for Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R
+ / -1), to differentiate the specific effects of glucocorticoid from the effects of
insulin resistance,

3. To compare these parameters between SCAT and VAT from Cushing patients. Methodology and
experimental design: non-randomized comparative multicenter study with constitution of
a biological collection.

Patients will be recruited in endocrinology before adrenalectomy and controls1 in urology.
They will have a preoperative assessment and sampling of perirenal AT and SCAT at surgery.
Controls2 are already included in the CRC2007-P050318 and will be drawn for matching.

Number of patients needed: We assume the relative gene expression of 11β-HSD1 in the VAT not
exposed to glucocorticoids = 0.81 ± 0.121. Our recruitment potential of Cushing patients is
30 patients. With 30 patients per group, we will be able to detect a difference in 11β-HSD1
gene expression in the VAT of Cushing patients at least 15% higher compared to controls1.