Variations in the DIO2 and MCT10 Genes and Effect of Triiodothyronine Treatment

Study Overview
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Brief Summary
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Hypothesis: Variations in the deiodinase 2 gene and monocarboxylate transporter 10 gene is associated with improvement in quality of life after initiation of combination therapy with L-Thyroxine and Liothyronine in patients with persistent hypothyroid symptoms despite conventional L-thyroxine mono-therapy. Purpose: To re-test this hypothesis in patients with continued perceived effect of Liothyronine treatment at least one year after initiation in a patient population more representing of daily clinical practice. The study will help determine whether testing of specific gene variations might predict longtime effect of combination therapy.

Official Title
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Longtime Effect of Combination Treatment With L-thyroxine (L-T4) and Liothyronine (L-T3) in Patients With Persistent Hypothyroid Symptoms - Relation to Polymorphisms (SNP) in the DIO2 and the MCT10 Gene

Conditions
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Hypothyroidism

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the department of endocrinology with the diagnose hypothyroidism because of persistent hypothyroid symptoms despite treatment with L-thyroxine mono-therapy and normal and stable TSH (for at least 6 months). Started in combination therapy with L-thyroxine and Liothyronine in an approximately 17/1 ratio Exclusion of an alternative explanation for persistent hypothyroid symptoms Exclusion Criteria: Initiation of L-thyroxine treatment in patients with s-TSH below upper normal limit (with assay in current use, that is TSH < 4 mU/L) Ongoing pregnancy Age below 18 years or above 80 years. Patients who do not read and understand information material given Patients who are not competent to give informed consent

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 |
| --- | --- |
| Responders<br>Patients in combination therapy due to persistent symptoms on L-thyroxin mono-therapy who experience a longtime effect of triiodothyronine treatment. | |
| Non-responders<br>Patients who have tried combination therapy due to persistent symptoms on L-thyroxin mono-therapy, but did not experience a longtime effect. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polymorphisms in DIO2/MCT10 and triiodothyronine treatment | Group 1(responders) and group 2(non-responders) are compared with regard to polymorphisms in the DIO2 gene and the MCT10 gene. Polymorphisms will be determined from DNA in a blood sample | Single assessment point, from 1-10 years after initiation of combination therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion treated with triiodothyronine | How many patients are treated with triiodothyronine at least one year after initiation of combination therapy. | Single assessment point, from 1-10 years after initiation of combination therapy | 
| Quality of life questionnaire | Patients are scored on the ThyPRO questionnaire and a hypothyroid symptoms questionnaire. | Single assessment point, from 1-10 years after initiation of combination therapy | 
| Who controls the treatment? | Patients report whether treatment is controlled by 1) a general practitioner 2) Patient self 3) other type of healthcare professional 4) a certified endocrinologist or 5) other | Single assessment point, from 1-10 years after initiation of combination therapy | 
| How is current treatment controlled? | Patients report if current treatment is for example controlled by using blood samples or only on the basis of symptoms. | Single assessment point, from 1-10 years after initiation of combination therapy | 
| Have therapy changed after the patient left the department of endocrinology? | Current hypothyroidism treatment and doses of medication | Single assessment point, from 1-10 years after initiation of combination therapy | 
| TSH | Is the patient well regulated? Normal TSH: 0.1-4.0 (depending on assay used). Over-treatment: TSH < 0.1 (depending on assay used). Under-treatment: TSH>4 (depending on assay used). | Single assessment point, from 1-10 years after initiation of combination therapy | 
| Osteoporosis | DXA-scan | Single assessment point, from 1-10 years after initiation of combination therapy | 
| Risk of arrhythmia | Puls and blood pressure is measured. If arrhythmia is suspected, an ECG is performed. | Single assessment point, from 1-10 years after initiation of combination therapy |