ReviewThe Journal of clinical endocrinology and metabolism2020
Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Review in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
42 citing papers in PubMed, 4 syntheses or guidelines pooled it, 73 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
- Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- A Systematic Review and Meta-Analysis of Free Triiodothyronine (FT3) Levels in Humans Depending on Seasonal Air Temperature Changes: Is the Variation in FT3 Levels Related to Nonshivering Thermogenesis?International journal of molecular sciences · 2023Pooled it
- Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2021Trial
- Histidine alleviates Hashimoto's thyroiditis via the neutrophil extracellular traps-NF-κB signaling pathway.Scientific reports · 2026Article
- The type 2 deiodinase Thr92Ala polymorphism and cognitive aging: current evidence and biological context.Therapeutic advances in endocrinology and metabolism · 2026Review
- Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism.Journal of endocrinological investigation · 2025Article
- Article
- Levothyroxine dose prediction post-thyroidectomy for differentiated thyroid carcinoma.Frontiers in endocrinology · 2025Article
- Self-Management and Support Needs of Patients Experiencing Persistent Symptoms Consistent With Hypothyroidism: A Qualitative Study.Journal of patient-centered research and reviews · 2025Article
- Persistent symptoms in euthyroid Hashimoto's thyroiditis: current hypotheses and emerging management strategies.Frontiers in endocrinology · 2025Review
- Metabolic Consequences of Thyroidectomy and Patient-Centered Management.Journal of clinical medicine · 2024Review
- Reviving ancient therapeutics in modern medicine: an immunological and biological narrative review of wet cupping in the management of Hashimoto's thyroiditis.Gland surgery · 2024Review
- The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders.Molecular neurobiology · 2024Article
- Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism.Endocrine · 2024Review
- Article
- Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey.Journal of clinical & translational endocrinology · 2024Article
- Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Emerging Therapies in Hypothyroidism.Annual review of medicine · 2024Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
contextIt is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. EVIDENCE ACQUISITION: This review is based on a collection of primary and review literature gathered from a PubMed search of "hypothyroidism," "levothyroxine," "liothyronine," and "desiccated thyroid extract," among other keywords. PubMed searches were supplemented by Google Scholar and the authors' prior knowledge of the subject. EVIDENCE SYNTHESIS: In most LT4-treated patients, normalization of serum thyrotropin levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, for example, specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels.
conclusionsAfter excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients who have persistent symptoms or metabolic abnormalities despite normalization of serum thyrotropin level. New clinical trials focused on symptomatic patients, genetic makeup, and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.
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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.