Lopend onderzoek
Background
Approximately 15% of patients with hypothyroidism treated with levothyroxine (LT4) monotherapy continue to experience persistent symptoms, despite normalized thyroid hormone levels. Debilitating fatigue is the most frequently reported complaint.
This national multicenter study includes patients with severe, long-lasting fatigue despite LT4 use. The aim of the study is to determine whether combination therapy with LT4 and liothyronine (LT3) is effective in improving quality of life.
Objective
The primary objective is to assess whether adding the thyroid hormone T3 to standard T4 (levothyroxine) therapy can reduce fatigue and possibly other related symptoms. In addition, the study will explore whether specific patient characteristics can help predict who is likely to benefit from T4/T3 combination therapy in the future.
Inclusion Criteria
- Age ≥ 18 years
- (Subclinical or overt) primary hypothyroidism*
- At least 6 months of LT4 monotherapy (dose between 75–225 mcg, ≥1.2 mcg/kg/day)
- TSH within normal range during the past 3 months
- Severe fatigue for ≥ 6 months with a negative impact on daily life
- Sufficient proficiency in Dutch (spoken and written)
* Positive TPO/Tg antibodies are not required. Autoimmune hypothyroidism is ensured by excluding other causes.
Exclusion Criteria- Congenital hypothyroidism or (sub)acute thyroiditis (except postpartum thyroiditis)
- Secondary (central) hypothyroidism
- History of thyroid surgery, radioactive iodine treatment, or head/neck radiotherapy
- Current or prior use of: amiodarone, lithium, immunotherapy, tyrosine kinase inhibitors, interferon, corticosteroids, or dopamine
- Treatment in specialized psychiatric care (basic mental health care is allowed)
- Clinical diagnosis of dementia
- Pregnancy, breastfeeding, or pregnancy planned within 2 years
- Women of childbearing age not using reliable contraception and without a sterilized partner
- Atrial fibrillation (current or previous)
- Structural or functional heart disease, or conduction abnormalities (QRS >120 ms or prolonged QTc)
- Frequent ventricular extrasystoles or ventricular tachycardia
- Recent acute coronary syndrome (< 4 weeks)
- Other somatic causes of fatigue (e.g., end-stage renal disease, COPD GOLD IV, malignancy)
- Major life events that could plausibly explain fatigue (e.g., bereavement, divorce, job loss)
For questions, please contact the central study team at:
t3hypotrial@erasmusmc.nl
