Een nieuwe terugblik op het gebruik van T4 plus T3

De meeste patiënten met hypothyreoïdie slikken alleen LT4 (levothyroxine). Dat is de standaardbehandeling. Een deel van de patiënten houdt restklachten na het optimaal instellen op levothyroxine. Soms proberen deze patiënten en hun artsen of aanvullend LT3-hormoon (liothyronine) verbetering geeft van deze restklachten. Een naar schatting kleine groep patiënten voelt zich beter met deze combinatiebehandeling.
Effects of long-term combination LT4 and LT3 therapy for improving hypothyroidism and overall quality of life
Anam Tariq, Yijin Wert, Pramil Cheriyath, Renu Joshi

T4  plus  T3 combinatie behandeling: is er echt een effect?

Hypothyroidism results in decreased mood and neurocognition, weight gain, fatigue, and many other undesirable symptoms. The American Association of Clinical Endocrinologists, the American Thyroid Association (ATA), and The Endocrine Society recommend levothyroxine (LT4) monotherapy as the treatment for hypothyroidism; however, after years of monotherapy, some patients continue to experience impaired quality of life. Combination LT4 and synthetic liothyronine (LT3) therapy or the use of desiccated thyroid extract (DTE), has not been suggested for this indication based on short-duration studies with no significant benefits. Our first observational study examined the role of combination therapy for 6 years in improving quality of life in a subset of a hypothyroid population without adverse effects and cardiac mortality.


An observational retrospective study examining patients prescribed thyroid replacements with serum triiodothyronine (FT3), LT4 with LT3 (synthetic therapy) or DTE (natural therapy), compared with LT4 alone in the United States from 2010 to 2016. Thyroid-stimulating hormone (TSH), serum thyroxine (FT4), and FT3 levels were documented for each patient in addition to any admissions of myxedema coma, thyrotoxicosis, or cardiovascular complications, such as arrhythmias, atrial fibrillation, and mortality. At the conclusion of the study, a cross-sectional interview assessed quality of life for each combination therapy through the Medical Outcomes Study Short Form-20 questionnaire.


Compared with patients taking only LT4, 89.47% using synthetic therapy had therapeutic TSH. Similarly, 96.49% using natural therapy had therapeutic TSH. Less than 5% of patients had supratherapeutic FT3. None of the patients who had abnormally low TSH or elevated FT3 or FT4 levels had hospitalizations for arrhythmias or thyrotoxicosis. On the Medical Outcomes Study Short Form-20 questionnaire, 92% answered feeling “excellent, very good, or good” when questioned about their health while undergoing thyroid replacement compared with levothyroxine alone.


Combination therapy of LT4 and LT3 has remained an experimental treatment that can be used at the physician’s discretion. Our observational study concludes that for a subset of patients who feels suboptimal on LT4 monotherapy, synthetic therapy is beneficial and safe in controlling hypothyroid symptoms and improving quality of life. We are hopeful that our analysis will raise awareness and promote further RCTs focusing on appropriate dosages and populations. An interesting future study should be to compare the practices of endocrinologists and primary care physicians in their management of patients undergoing combination therapy.

Key Points

  • Even after years of levothyroxine monotherapy, some patients believe that they still have an impaired quality of life.
  • The meta-analysis of combination therapy has been negative for combination therapy in managing hypothyroidism, and the data reported on some general well-being questionnaires also are inconclusive.
  • Low levels of 25[OH] vitamin D, vitamin B12, and hemoglobin were checked in our study to rule out other causes of fatigue and hypothyroidism before starting combination therapy because they have not been ruled out in previous literature.
  • In our population, the symptoms of hypothyroidism improved significantly as reported on follow-up encounters with subsequent improvement in laboratory thyroid function studies and questionnaires, and furthermore, not resulting in hyperthyroidism that caused hospitalizations for medication adverse effects, arrhythmias, or cardiac death.