Cardiac Steatosis in Cushing's Syndrome

Study Overview
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Brief Summary
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This study aims at evaluating the myocardial triglyceride content and cardiac structure and function, using 1H magnetic resonance spectroscopy and cardiac magnetic resonance imaging, in patients with Cushing's syndrome before and after treatment and in age-, sex- and BMI-matched healthy volunteers. The investigators make the hypothesis that Cushing's syndrome patients compared to healthy subjects present with excess lipid storage in cardiac myocytes, reversible upon correction of hypercortisolism.

Detailed Description
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Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased Left Ventricular mass, reversible upon correction of the hypercortisolism. This may be due to cardiac steatosis, previously demonstrated in patients with diabetes mellitus. This study aims at evaluating the myocardial triglyceride content and cardiac structure and function, using 1H magnetic resonance spectroscopy and cardiac magnetic resonance imaging (CMRI), in patients with Cushing's syndrome and in age-, sex- and BMI-matched healthy volunteers. The patients will be stratified into two groups in function of the presence or absence of diabetes mellitus or impaired glucose and will be evaluated twice: before and 6 months after efficient treatment of Cushing's syndrome. We make the hypothesis that Cushing's syndrome patients compared to healthy subjects have excess lipid storage in cardiac myocytes irrespectively of the glucose homeostasis status, and that this lipid content will decrease after the correction of hypercortisolism.

Official Title
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Evaluation of Cardiac Steatosis in Cushing's Syndrome. A 1H-Magnetic Resonance Spectroscopy Study

Conditions
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Endocrine System Disease, Cardiovascular Imaging

Intervention / Treatment
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* Other: 1H magnetic resonance spectroscopy and CMRI
* Other: 1H magnetic resonance spectroscopy and CMRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: group 1 and 2: patients with overt Cushing's syndrome, with 24-hour urinary free cortisol excretion over the two fold of the upper limit of the normal, with (group 1) or without (group 2) diabetes mellitus or glucose intolerance group 3: healthy volunteers matched for age, sex and BMI with the patients of the group 2 Exclusion Criteria: contraindication of MRI hypersensitivity to gadolinium acute myocardial ischemia renal insufficiency (creatinin clearance 30 mL/min/l,73m2) pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 : 1H magnetic resonance spectroscopy and CMRI<br>Group 1 : Cushing's syndrome patients with diabetes mellitus or glucose intolerance | Other: 1H magnetic resonance spectroscopy and CMRI<br>* Metabolic status of the patients evaluated by an OGTT (measuring plasma glucose, insulin and plasma nonesterified fatty acids concentrations) and myocardial Imaging and spectroscopy will be performed before and 6 month after treatment<br>* Other names: Before and after Treatment;|
| Experimental: Group 2 : 1H magnetic resonance spectroscopy and CMRI<br>Group 2: Cushing's syndrome patients with normal glucose intolerance | Other: 1H magnetic resonance spectroscopy and CMRI<br>* Metabolic status of the patients evaluated by an OGTT (measuring plasma glucose, insulin and plasma nonesterified fatty acids concentrations) and myocardial Imaging and spectroscopy will be performed before and 6 month after treatment<br>* Other names: Before and after Treatment;|
| Experimental: Group 3 : 1H magnetic resonance spectroscopy and CMRI<br>age-, sex- and BMI-matched healthy volunteers | Other: 1H magnetic resonance spectroscopy and CMRI<br>* Metabolic status of the patients evaluated by an OGTT (measuring plasma glucose, insulin and plasma nonesterified fatty acids concentrations) and myocardial Imaging and spectroscopy will be performed before treatment<br>* Other names: Once;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular (LV) intramyocardial triglyceride / water ratio LV intramyocardial triglyceride / water ratio | Intramyocardial triglyceride content will be assessed by 1H magnetic resonance spectroscopy | Assessed twice in patients - before and 6 months after treatment - and once in volunteers | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular intramyocardial fatt fraction (Dixon) | In/Out of Phase Imaging (Dixon) | Assessed twice in patients - before and 6 months after treatment - and once in volunteers | 
| Subcutaneous and visceral abdominal fatt | ISubcutaneous and visceral abdominal fat masses were determined from abdominal axial images at the L3 to L4 level | Assessed twice in patients - before and 6 months after treatment - and once in volunteers | 
| Cardiac morphology and function | LV mass index, LA, LV and Right Ventricular (RV) ejection fractions and LV and RV stroke volumes assessed by Cardiac Magnetic Resonance Imaging (CMRI) | Assessed twice in patients - before and 6 months after treatment - and once in volunteers | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing's syndrome, cardiac steatosis, intramyocardial triglyceride content, 1H magnetic resonance spectroscopy and cardiac magnetic resonance imaging, Left Ventricularly hypertrophy