ReviewEndocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2023
Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?
Review in Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Treatment of Hypothyroidism That Contains Liothyronine is Associated With Reduced Risk of Dementia and Mortality.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- LT4/LT3 Combination Therapy vs. Monotherapy with LT4 for Persistent Symptoms of Hypothyroidism: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Association between maternal thyroid dysfunction and neurodevelopmental disorders in offspring: a population-based cohort study.European child & adolescent psychiatry · 2026Article
- Association between thyroid feedback quartile index and FIB-4-defined fibrosis risk in patients with metabolic dysfunction-associated steatotic liver disease, type 2 diabetes mellitus, and treated primary hypothyroidism: an exploratory cross-sectional study.Frontiers in endocrinology · 2026Article
- Variable transduction of thyroid hormone signaling in structures of the mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Correlation of Residual Symptoms With Triiodothyronine (T3) in Patients Treated for Hypothyroidism.Cureus · 2025Article
- The Association Between Hypothyroidism and Cognitive Function Change in Women across the Menopause Transition: The Study of Women's Health Across the Nation.Thyroid : official journal of the American Thyroid Association · 2024Article
- Mapping Thyroid Hormone Action in the Human Brain.Thyroid : official journal of the American Thyroid Association · 2024Review
- Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism.Journal of physiology and biochemistry · 2024Review
- Emerging Therapies in Hypothyroidism.Annual review of medicine · 2024Review
- Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy.Frontiers in endocrinology · 2024Article
- Daily Intramuscular Levothyroxine in Refractory Hypothyroidism and Malabsorption.AACE endocrinology and diabetesArticle
- Review
- Clinical Use and Perception About Synthetic Liothyronine for the Treatment of Primary Hypothyroidism Among Healthcare Professionals in India.Indian journal of endocrinology and metabolismArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
introductionLevothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life.
objectiveTo provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment.
methodsWe reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3).
resultsA score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided.
conclusionA recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.
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Identifiers
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.