Hypothyroidism, Metabolism and Food Intake

Study Overview
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Brief Summary
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This project has the following primary aims: To measure changes in appetite and food intake in newly diagnosed hypothyroid patients during the first six months after starting levothyroxine (L-T4) substitution therapy Secondary aims are: To delineate the effect of L-T4 substitution therapy on thyroid status, body weight, body mass index (BMI), body composition, physical activity, glycaemic control, postprandial gut and pancreatic hormone responses, gastric and gall bladder emptying, resting energy expenditure (REE), quality of life (QOL) and cognitive function

Detailed Description
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18 newly diagnosed hypothyroid female patients and 18 healthy controls age between 20 and 75 years will be recruited from the out-patients clinic in Herlev and Gentofte Hospital and the general practitioners before start of substitution therapy. The study is devided in to three identical experimental days of approx. 6 hours. First experimental day placed before T4 treatment is initiated. Second day as soon as Thyroid Stimulating Hormone (TSH) is below 4 milli unit pr liter (mU/l). The Third experimental day after 6 months of T4 therapy. For 5-7 days before each experimental day, the participants' physical activity energy expenditure (PAEE) will be monitored by an Actiheart® pedometer attached to the skin of the chest. The last two days before each experimental day, the participants will follow a standardised diet following World Health Organization guidelines on energy requirements and nutrient composition according to gender, age and body weight Shortly after diagnosis patients will undergo a test panel at the first experimental day, where patients arrives fasting. Visual analog score on satiety and thirst will be filled out continuously. REE will be measured by a CCM-express calorimeter, Dual Energy X-ray absorptiometry (DEXA)-scan Blood samples will be taken continuously during the experimental day. Gall bladder size will be examined at 6 times during the experimental day using ultra sound. At the end of the day, patients´ satiety will be examined with an ad libitum meal. Blood will be analysed for Gastric inhibitory polypeptide (GIP), Glucagon-like Peptide 1 (GLP-1), Glucagon-like Peptide 2 (GLP-2), glucagon, peptide tyrosine tyrosine (PYY), Gastrin, Cholesystokinin (CCK), Insulin, C-peptide, Blood sugar, Cholesterol, Free fatty acids and paracetamol.

Official Title
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Levothyroxine Substitution Therapy in Hypothyroid Patients - Impact on Appetite and Food Intake

Conditions
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Hypothyroidism

Intervention / Treatment
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* Drug: Levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: TSH > 10 Female Exclusion Criteria: Competing serious disease Male Not able to understand written and spoken danish Pregnancy Thyroidectomized patients Amiodarone treatment.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Hypothyroid patients<br>Hypothyroid patients treated with Levothyroxine as part of normal treatment. | Drug: Levothyroxine<br>* Normal treatment with levothyroxine.<br>* Other names: Eltroxin/Euthyrox;|
| Healthy volunteers<br>Matched on age and BMI. 18 Persons. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in food intake at ad libitum meal | Changes in food intake at ad libitum meal measured at each experimental day | 6 months | 
| Satiety | Satiety measured on a visual analog score 13 times during each experimental day. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lean mass assessed through lean mass | Changes in lean mass assessed through lean mass with DEXA-scan | 6 months | 
| Changes in fat mass assessed through lean mass with DEXA-scan | Changes in lean mass assessed through lean mass with DEXA-scan | 6 months | 
| Changes in gall bladder emptying | Changes in gall bladder emptying evaluated with ultrasound 6 times each experimental day before and after meal. | 6 months | 
| Changes in resting energy expenditure | Changes in resting energy expenditure measured 3 times each experimental day using Indirect Calorimetry. | 6 months | 
| Changes in blood sugar response to standardized meal. | changes in blood sugar response to standardized meal measured before and after meal at each experimental day. | 6 Months | 
| Changes in stomach emptying | Evaluated with continously measuring serum paracetamol after standardized meal containing 1,5 g paracetamol. | 6 months | 
| Changes in GIP hormones | Continously measuring of a range of hormones during each experimental day: GIP | 6 months | 
| Changes in GLP-1 hormones | Continously measuring of GLP-1 hormones during each experimental day | 6 months | 
| Changes in GLP-2 hormones | Continuously measuring of GLP-2 hormones during each experimental day | 6 Months | 
| Changes in PYY hormones | Continuously measuring of PYY hormones during each experimental day | 6 Months | 
| Changes in CCK hormones | Continuously measuring of CCK hormones during each experimental day | 6 Months | 
| Changes in Gastrin hormones | Continuously measuring of Gastrin during each experimental day | 6 Months | 
| Changes in Insulin hormones | Continuously measuring of Insulin during each experimental day | 6 Months | 
| Changes in Glucagon | Continuously measuring of Glucagon during each experimental day | 6 Months | 
| Changes in C-peptide | Continuously measuring of C-peptide during each experimental day | 6 Months | 
| Changes in Free-Fatty acids | Continuously measuring of Free Fatty acids during each experimental day | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body Composition, Food intake, Resting Energy Expenditure, Gall Bladder emptying, Insulin response