ReviewEndocrine2019
T4 + T3 combination therapy: any progress?
Review in Endocrine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Benefits and Harms of Levothyroxine/L-Triiodothyronine Versus Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-Analysis.Thyroid : official journal of the American Thyroid Association · 2021Pooled it
- Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study.Frontiers in endocrinology · 2022Trial
- The Chronobiology of Hormone Administration: "Doctor, What Time Should I Take My Medication?"Endocrine reviews · 2025Review
- Article
- Increased Absorption of Thyroxine in a Murine Model of Hypothyroidism Using Water/COInternational journal of molecular sciences · 2024Article
- Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey.Journal of clinical & translational endocrinology · 2024Article
- Severity of hypothyroidism is inversely associated with impaired quality of life in patients referred to an endocrine clinic.Thyroid research · 2023Article
- Thyroid Hormone Abuse in Elite Sports: The Regulatory Challenge.The Journal of clinical endocrinology and metabolism · 2022Review
- Redefinition of Successful Treatment of Patients With Hypothyroidism. Is TSH the Best Biomarker of Euthyroidism?Frontiers in endocrinology · 2022Review
- Subclinical thyroid dysfunction and major depressive disorder.Hormones (Athens, Greece) · 2021Review
- T3 therapy in hypothyroidism. Still more questions than answers.Archives of endocrinology and metabolism · 2021Article
- What Is the Quality of Life in Patients Treated with Levothyroxine for Hypothyroidism and How Are We Measuring It? A Critical, Narrative Review.Journal of clinical medicine · 2021Review
- Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.European thyroid journal · 2021Article
- Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study.Clinical kidney journal · 2021Article
- Time to Euthyroidism and Its Determinants Among Thyrotoxicosis Patients on Anti-Thyroid Drug Who Attend to Medical and Ambulatory Clinics of South Tigrai General Hospitals.Therapeutics and clinical risk management · 2021Article
- LT4 and Slow Release T3 Combination: Optimum Therapy for Hypothyroidism?International journal of endocrinology and metabolism · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Guidelines on T4 + T3 combination therapy were published in 2012. This review investigates whether the issue is better understood 7 years later. Dissatisfaction with the outcome of T4 monotherapy remains high. Persistent symptoms consist mostly of fatigue, weight gain, problems with memory and thinking and mood disturbances. T4 monotherapy is associated with low serum T3 levels, which often require TSH-suppressive doses of L-T4 for normalization. Peripheral tissue thyroid function tests during T4 treatment indicate mild hyperthyroidism at TSH < 0.03 mU/L and mild hypothyroidism at TSH 0.3-5.0 mU/L; tissues are closest to euthyroidism at TSH 0.03-0.3 mU/L. This is explained by the finding that whereas T4 is usually ubiquinated and targeted for proteasomal degradation, hypothalamic T4 is rather stable and less sensitive to ubiquination. A normal serum TSH consequently does not necessarily indicate a euthyroid state. Persistent symptoms in L-T4 treated patients despite a normal serum TSH remain incompletely understood. One hypothesis is that a SNP (Thr92Ala) in DIO2 (required for local production of T3 out of T4) interferes with its kinetics and/or action, resulting in a local hypothyroid state in the brain. Effective treatment of persistent symptoms has not yet realized. One may try T4 + T3 combination treatment in selected patients as an experimental n = 1 study. The 2012 ETA guidelines are still valid for this purpose. More well-designed randomized clinical trials in selected patients are key in order to make progress. In the meantime the whole issue has become rather complicated by commercial and political overtones, as evident from skyrocketing prices of T3 tablets, aggressive pressure groups and motions in the House of Lords.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.