Observational studyThe Journal of clinical endocrinology and metabolism2023
Serum Thyrotropin and Triiodothyronine Levels in Levothyroxine-treated Patients.
Observational study in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis 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, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism.European thyroid journal · 2025Guideline
- A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism.Frontiers in endocrinology · 2025Trial
- Review
- Thyroid Hormone Synthesis Without Thyroglobulin.Thyroid : official journal of the American Thyroid Association · 2026Article
- Evaluating the Link Between Thyroid Function Test Results and Levothyroxine Dose in the Management of Hypothyroidism: Can We Improve Dosing Regimes?Clinical endocrinology · 2026Article
- Measuring Hypothyroidism Disease Control Using a TSH-based "Time-in-range".The Journal of clinical endocrinology and metabolism · 2026Article
- Evaluation of harmonization among thyroid hormone testing systems: A comparative study based on external quality assessment data.Practical laboratory medicine · 2025Article
- How Does Thyroid Hormone Profile Differ on and Off Replacement Treatment?Clinical endocrinology · 2025Article
- 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
- Levothyroxine therapy in thyroidectomized patients: ongoing challenges and controversies.Frontiers in endocrinology · 2025Review
- Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.The Journal of clinical endocrinology and metabolism · 2024Article
- Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism.Endocrine · 2024Review
- Emerging Therapies in Hypothyroidism.Annual review of medicine · 2024Review
- Longevity, demographic characteristics, and socio-economic status are linked to triiodothyronine levels in the general population.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.Endocrinology · 2023Article
- Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2023Review
- Hypothyroidism: The difficulty in attributing symptoms to their underlying cause.Frontiers in endocrinology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
contextSmall adjustments in levothyroxine (LT4) dose do not appear to provide clinical benefit despite changes in thyrotropin (TSH) levels within the reference range. We hypothesize that the accompanying changes in serum total triiodothyronine (T3) levels do not reflect the magnitude of the changes in serum TSH.
objectiveThis work aims to characterize the relationships of serum free thyroxine (FT4) vs T3, FT4 vs TSH, and FT4 vs the T3/FT4 ratio.
methodsThis cross-sectional, observational study comprised 9850 participants aged 18 years and older treated with LT4 from a large clinical database from January 1, 2009, to December 31, 2019. Patients had been treated with LT4, subdivided by serum FT4 level. Main outcome measures included model fitting of the relationships between serum FT4 vs TSH, FT4 vs T3, and FT4 vs T3/FT4. Mean and median values of TSH, T3, and T3/FT4 were calculated.
resultsThe relationships T3 vs FT4 and TSH vs FT4 were both complex and best represented by distinct, segmented regression models. Increasing FT4 levels were linearly associated with T3 levels until an inflection point at an FT4 level of 0.7 ng/dL, after which a flattening of the slope was observed following a convex quadratic curve. In contrast, increasing FT4 levels were associated with steep declines in TSH following 2 negative sigmoid curves. The FT4 vs T3/FT4 relationship was fit to an asymptotic regression curve supporting less T4 to T3 activation at higher FT4 levels.
conclusionIn LT4-treated patients, the relationships between serum FT4 vs TSH and FT4 vs T3 across a range of FT4 levels are disproportionate. As a result, dose changes in LT4 that robustly modify serum FT4 and TSH values may only minimally affect serum T3 levels and result in no significant clinical benefit.
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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.