Metabolomics of Thyroid Hormones

Study Overview
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Brief Summary
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The aim of this study is to develop a metabolome signature of thyroid hormone status. The metabolome signature could be useful in diagnosis and treatment of thyroid dysfunction diseases, especially in cases where TSH cannot be reliably used.

Detailed Description
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Primary Hypothyroidism is a frequent endocrine disorder, where the thyroid gland does not produce sufficient amounts of thyroid hormones. The substitution therapy is guided by measurement of the pituitary gland hormone thyrotropin (TSH). Patients with central hypothyroidism in whom pituitary insufficiency leads to hypothyroidism, TSH cannot be used to guide therapy. So far there are no reliable methods for therapy control in patients with central hypothyroidism. The measurement of small endogenous metabolites might give investigators a metabolomics profile. This could help to discriminate between euthyroid, hypothyroid and hyperthyroid state and therefore could be used for diagnosis and therapy control of thyroid dysfunction diseases.

Official Title
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Metabolomics of Thyroid Hormones

Conditions
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Central Hypothyroidism, Hypothyroidism, Hyperthyroidism

Intervention / Treatment
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* Diagnostic Test: Indirect calorimetry
* Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)
* Diagnostic Test: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants: Age 18 to 80 years BMI 19 to 35 kg/m2 Informed consent as documented by signature A) Patients with primary hyperthyroidism TSH < 0.2 mIU/l and free thyroxine (fT4) > 25 pM or fT3 > 8 pM B) Patients with primary hypothyroidism, currently not sufficiently substituted TSH > 8 milli-International unit (mIU)/l or fT4 < 10 pM C) Patients with diagnosis of primary hypothyroidism, sufficiently substituted Documented diagnosis of primary hypothyroidism Substitution with L-Thyroxin TSH in target range between 0.5 and 2.5 mIU/l D) Patients with secondary hypothyroidism Pituitary disease with documented secondary hypothyroidism Exclusion Criteria: Diabetes mellitus (HbA1c >6.5%) Severe concomitant diseases: chronic heart failure, liver cirrhosis, kidney failure, active cancer Abuse of alcohol or illicit drugs Women who are pregnant or breast feeding Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Previous enrolment into the current study

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br>Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) Indirect calorimetry Dual energy X-ray Absorptiometry (DXA) | Diagnostic Test: Indirect calorimetry<br>* Resting energy expenditure<br>Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)<br>* Body composition<br>Diagnostic Test: Blood sampling<br>* fT4, fT3, TSH, HDL, LDL, triglycerides, cholesterol, HbA1c, Glucose Thyroid panel<br>|
| Patients with thyroid dysfunction<br>Patients with Primary hypothyroidism newly diagnosed, Primary hypothyroidism substituted, hyperthyroidism, secondary hypothyroidism Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) Indirect calorimetry Dual energy X-ray Absorptiometry (DXA) | Diagnostic Test: Indirect calorimetry<br>* Resting energy expenditure<br>Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)<br>* Body composition<br>Diagnostic Test: Blood sampling<br>* fT4, fT3, TSH, HDL, LDL, triglycerides, cholesterol, HbA1c, Glucose Thyroid panel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolome signature of thyroid Hormone Status (MSTH) | The MSTH will be tested against the current standard of diagnosis which is serum TSH level by multiple linear regression. | baseline/single visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting energy expenditure (REE) | Comparison of REE of healthy volunteers and Patients with thyroid dysfunction, measured by indirect calorimetry. | baseline/single visit | 
| Body composition concerning muscle mass | Comparison of muscle mass of healthy volunteers and patients with thyroid dysfunction, measured by DXA | baseline/single visit | 
| Body composition concerning fat mass | Comparison of fat mass of healthy volunteers and patients with thyroid dysfunction, measured by DXA | baseline/single visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypothyroidism, Metabolomics, Thyroid Hormones, Hyperthyroidism