Brown Adipose Tissue Activity and Thyroid Hormone

Study Overview
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Brief Summary
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Rationale: During the last decades, research in possible therapies for existing obesity and developmental factors causing obesity has explosively increased. Recently renewed interest aroused for a tissue playing a possible role in both development and therapy for obesity: brown adipose tissue (BAT). To define the relation between BAT and thyroid hormone, the investigators set up the following research protocol. In this protocol BAT activity will be determined in subjects that underwent thyroidectomy for well-differentiated thyroid carcinoma. Objective: To study the effect of thyroid hormone and thyroid-stimulating hormone on brown adipose tissue activity. Study design: Determine BAT activity after thyroidectomy in well-differentiated thyroid carcinoma patients. Study population: Patients that underwent thyroidectomy for well-differentiated thyroid carcinoma, male and female, aged 18-65 years. Intervention: FDG-PET-CT-imaging ([18F]fluorodeoxyglucose positron-emission-tomography computed-tomography) of BAT activity will be performed under cold stimulation twice. For patients clinically withdrawn from thyroid hormone suppletion, the first occasion will be in a hypothyroid state within 4-6 weeks after thyroidectomy and the second measurement will take place in a euthyroid state 4 months after the start of thyroid hormone treatment. For patients receiving recombinant-thyroid-stimulating-hormone injections, the first occasion will be shortly after the injection in a state of high thyroid-stimulating hormone levels. The second measurement will be in a euthyroid state 4 months after the injection. Main study parameters/endpoints: The main endpoint of this study is the effect of thyroid hormone and thyroid-stimulating hormone on BAT activity in kBq (kilobecquerel) and SUV (standard uptake value). Secondary endpoints are the effects of thyroid hormone and thyroid-stimulating hormone on energy metabolism, body core temperature, skin surface temperatures and skin perfusion. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The absorbed radiation dose from the FDG PET-CT scan after administration of 74 MBq (megabecquerel) of 18F-FDG is 2.8 mSv (miliSievert).

Official Title
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Brown Adipose Tissue Activity and Thyroid Hormone

Conditions
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Hypothyroidism, Hyperthyroidism, Obesity

Intervention / Treatment
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* Other: Levothyroxine therapy (137.75 ± 23.75 μg/day)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or postmenopausal females undergoing a total thyroidectomy for well-differentiated thyroid carcinoma Age 18-65 years Stable physical activity levels for at least six months Note: In case of use of anticoagulation, the dose will be adjusted according to plasma thyroid hormone values. Exclusion Criteria: Psychologically unstable subjects (as judged by the treating medical specialist) Subjects with mental retardation (as judged by the treating medical specialist) Subjects with severe behavior disorders (as judged by the treating medical specialist) Pregnant subjects The use of the following medication is an exclusion criterium; ß-blockers Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study Abuse of drugs and/or alcohol Severe diabetes which requires application of insulin or patients with diabetes-related complications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Before levothyroxine therapy 137.75 μg<br>18F-FDG PET CT scan after mild cold exposure 6.8 ± 2.8 weeks after thyroidectomy, when plasma free T4-levels were at the minimum, before daily levothyroxine therapy 137.75 ± 25.75 μg. | Other: Levothyroxine therapy (137.75 ± 23.75 μg/day)<br>* This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to standard treatment protocol).<br>|
| Other: After levothyroxine therapy 137.75 μg<br>18F-FDG PET CT scan after mild cold exposure four to six months after the initial measurements, after daily levothyroxine therapy 137.75 μg (fT4 levels 23.1 ± 3.9 pmol/L, TSH 0.5 ± 0.6 mU/L) | Other: Levothyroxine therapy (137.75 ± 23.75 μg/day)<br>* This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to standard treatment protocol).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold-induced brown adipose tissue activity | Measured with 18FDG PET/CT scan after personalised cooling protocol | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy expenditure | Energy expenditure measured with ventilated hood system | 1 day | 
| Body core temperature | Body core temperature measured with CorTemp telemetric pill | 1 day | 
| Skin temperatures | Skin temperatures measured with iButton wireless dataloggers at 14 ISO-defined positions on the skin | 1 day | 
| Skin perfusion | Skin perfusion measured with laser-doppler flowmetry on hand and forearm | 1 day |