The Circadian Rhythm in CusHing SyndrOme in Active Phase and dUring RemiSsion (TheHOURS)

Study Overview
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Brief Summary
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This is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state.

Detailed Description
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Cushing Syndrome is a severe condition caused by prolonged exposure to high levels of glucocorticoids. This is a disease with high morbidity and mortality due to metabolic, cardiovascular, coagulative, psychiatric complications of hypercortisolism. The loss of circadian secretion of cortisol is one of the most sensitive and specific diagnostic features of Cushing's Syndrome that normalizes during remission. The evaluation of the circadian rhythm of cortisol is one of the diagnostic tests recommended by the guidelines to evaluate the state of the disease's activity. Studies in literature have shown several correlations between states of hypercortisolism and circadian secretion of melatonin, displaying reduced melatonin secretion throughout the day and the suppression of circadian rhythm of cortisol. However, the dynamics of the normalization of melatonin circadian rhythm during remission from Cushing syndrome are unclear. Therefore, the aim of our study is to evaluate the changes in circadian secretion of melatonin in Cushing's syndrome during active disease and during remission (3 and 6 months), according to the rational scientific influence of endogenous hypercortisolism on the function of the pineal gland. In addition, the changes in circadian secretion of cortisol, of mononuclear cells of the blood (PBMC) and of anthropometric-metabolic parameters, will be analyzed.

Official Title
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The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.

Conditions
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Cushing Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cushing Syndrome during active phase Exclusion Criteria: Malignancy Alcoholism or drug addiction Psychiatric disorders Clinical or laboratory signs of significant cardiovascular, hepatobiliary disease Clinically significant renal dysfunction Pregnancy Any medication with agents which could interfere with glucocorticoid kinetics and melatonin secretion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cushing Syndrome (active phase)<br>Patients displaying biochemical and clinical features of active Cushing's syndrome | |
| Cushing Syndrome (during remission)<br>Patients at 3-6 months from remission with cortisol levels in the normal range | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in measurement of melatonin secretion at 3 and 6 months | single outcome measurement of melatonin secretion | 0, +3 months, +6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of immunological profile at baseline, 3 and 6 months | composite outcome measure consisting of simultaneous measurement of: PBMC profiling with flow cytometry, Full count blood cell | 0, +3 months, +6 months | 
| Evaluation of cortisol circadian rhythm | single outcome measure of circadian cortisol secretion | 0, +3 months, +6 months | 
| Change from baseline in measurement of anthropometric-metabolic parameters at 3 and 6 months | composite outcome measure consisting of simultaneous measurement of:body weight (kg), waist circumference (cm), blood pressure and pulse | 0, +3 months, +6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing Syndrome, Adrenal Insufficiency, Peripheral blood mononuclear cells, Melatonin, Cortisol, Immunological profile, Cushing Disease