LT4/LT3 Combination Therapy Versus LT4 Monotherapy in Patients with Autoimmune Hypothyroidism.

Inclusion Criteria: * Patients with overt or subclinical primary hypothyroidism 18 years or older.\* * LT4 monotherapy for at least 6 months. * LT4 monotherapy dose of 75-225 microg, with at least a dose of 1.2 microg/kg. * TSH levels within the assay-specific reference ranges for at least 3 months. * Severe tiredness with a large negative impact on daily life for at least 6 months, with or without other persisting complaints. This is based on the patient's own experience, without judgment of the treating physician. * Sufficiently fluent in Dutch and able to read Dutch. * Thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibody positivity is not a requirement as these have frequently not been determined. Instead, we ensure that we only include patients with autoimmune hypothyroidism by excluding other causes of hypothyroidism (see exclusion criteria). Exclusion Criteria: * Congenital hypothyroidism, hypothyroidism after (sub)acute thyroiditis\*, secondary (central) hypothyroidism * Thyroid surgery, radioactive iodine treatment, or head and/or neck radiotherapy. * Use of thyroid interfering drugs (current/past use of amiodarone, immunotherapy, tyrosin kinase inhibitors, interferon, or lithium and current use of oral or iv corticosteroids or dopamine). * Current psychiatric disease treated at a "gespecialiseerde GGZ instelling"\*\* * Clinical diagnosis of dementia. * Pregnancy, breastfeeding or wish to become pregnant within 2 years. * Women of reproductive age not using adequate contraception, who are not sterilized and do not have a sterilized partner. Adequate contraceptives include the contraceptive pill, patch, injection, implant, intrauterine device or system, vaginal ring, diaphragm or cap, and condom. * Clinically relevant functional or structural abnormal heart (e.g., cardiomyopathy or valve disease) * Recent acute coronary syndrome or unstable angina pectoris (\<4 weeks) * Current/past atrial fibrillation * Current conduction disorder on ECG (i.e, QRS\>120 ms or prolonged QTc (women≥460 ms and men≥450 ms)). * Frequent ventricular extrasystole (=doublet, trigeminy, bigeminy or (non-sustained) ventricular tachycardia) in the past or on current ECG. * Other obvious medical explanation for tiredness (e.g. end-stage renal disease, anemia, COPD stage IV, cancer, etc.) * Other obvious major life event explanation for tiredness (e.g., mourning, loss of job) * Postpartum thyroiditis is not an exclusion criterium. * Treatments of mild non-complex psychological/psychiatric complaints are done in the " basis GGZ", e.g. consisting of conversations with a psychologist or psychotherapist, or via internet (e-health). "Gespecialiseerde GGZ" encompasses treatments of more severe psychological/psychiatric complaints. (link: Basis GGZ en gespecialiseerde GGZ \| Geestelijke gezondheidszorg (GGZ) \| Rijksoverheid.nl)