Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy
Open accessAbstract
OBJECTIVE: Hypothyroidism is relatively common, occurring in approximately 5% of the general US population aged ≥12 years. Levothyroxine (LT4) monotherapy is the standard of care. Approximately, 5%-10% of patients who normalise thyroid-stimulating hormone levels with LT4 monotherapy may have persistent symptoms that patients and clinicians may attribute to hypothyroidism. A long-standing debate in the literature is whether addition of levotriiodothyronine (LT3) to LT4 will ameliorate lingering symptoms. Here, we explore the evidence for and against LT4/LT3 combination therapy as the optimal approach to treat euthyroid patients with persistent complaints. METHODS: Recent literature indexed on PubMed was searched in March 2017 using the terms "hypothyroid" or "hypothyroidism" and "triiodothyronine combination" or "T3 combination." Relevant non-review articles published in English during the past 10 years were included and supplemented with articles already known to the authors. FINDINGS: Current clinical evidence is not sufficiently strong to support LT4/LT3 combination therapy in patients with hypothyroidism. Polymorphisms in deiodinase genes that encode the enzymes that convert T4 to T3 in the periphery may provide potential mechanisms underlying unsatisfactory treatment results with LT4 monotherapy. However, results of studies on the effect of LT4/LT3 therapy on clinical symptoms and thyroid-responsive genes have thus far not been conclusive. CONCLUSIONS: Persistent symptoms in patients who are biochemically euthyroid with LT4 monotherapy may be caused by several other conditions unrelated to thyroid function, and their cause should be aggressively investigated by the clinician.
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There is currently no accepted role for the use of LT3 in the management of hypothyroidism.
“there is currently no accepted role for the use of LT3 in the management of hypothyroidism”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [135]
Loss-of-function polymorphisms in deiodinases have been proposed to contribute to failure of thyrotropin-guided LT4 therapy to completely abolish symptoms of hypothyroidism in some patients, due to insufficient provision of T3.
“Loss-of-function polymorphisms in deiodinases have been proposed to contribute to failure of thyrotropin-guided LT4 therapy to completely abolish symptoms of hypothyroidism in some patients, due to insufficient provision of T3”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [135]
Results of trials comparing LT4-LT3 combinations with LT4 monotherapy, or meta-analyses of these trials, have been inconsistent, without demonstrating convincing or consistent benefit for combination therapy.
“The results of trials comparing LT4-LT3 combinations with LT4 monotherapy, or meta-analyses of these trials, have been inconsistent, without demonstrating convincing or consistent benefit for combination therapy”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [135]
Loss-of-function polymorphisms in deiodinases have stimulated interest in LT4-levotriiodothyronine combination therapy, or thyroid extracts, in patients with hypothyroidism.
“This has stimulated interest (and use to this day) in LT4-levotriiodothyronine (liothyronine, LT3) combination therapy, or thyroid extracts (which are not supported by any guidelines), in these patients”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [135]
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Self-citation
- Authors
- Hennessey, J. V., & Espaillat, R.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- AbbVie (United States) (US)
- Corresponding author
- Hennessey, James V.
- ORCID
- Hennessey, James V.
- Venue
- International Journal of Clinical Practice
- Publisher
- Wiley
- Published
- 2018-01-30
- Volume
- 72
- Issue
- 2
- Pages
- e13062
- ISSN
- 1368-5031 (ISSN-L)
- PMC
- PMC5873391
- OpenAlex
- W2791861988
- Cited by
- 49
- References
- 73
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 11 · 2020: 1 · 2019: 11 · 2018: 5
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Clinical Practice (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- AbbVie
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- hypothyroidism, levothyroxine, combination thyroid hormone therapy, thyroid-stimulating hormone
- MeSH terms
- Drug Therapy, Combination, Humans, Hypothyroidism, Thyroxine, Triiodothyronine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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