Triiodothyronine alongside levothyroxine in the management of hypothyroidism?
Open accessAbstract
The current guideline-based management of hypothyroidism recommends monotherapy with levothyroxine (LT4), titrated to maintain the level of thyrotropin within a euthyroid reference range. This has been successful for most people with hypothyroidism, but a substantial minority still report symptoms of hypothyroidism unexplained by a comorbid medical condition. LT4 is essentially a prodrug for triiodothyronine (T3), the thyroid hormone that acts on target tissues in the brain and the periphery. Thyroid hormone replacement with LT4 alone does not restore physiological tissue levels of thyroid hormones, particularly T3. During the last two decades, much interest has focussed on the potential of combinations of LT4 and T3 to provide a superior outcome to LT4 monotherapy for people with hypothyroidism, especially those with residual symptoms despite thyrotropin-optimized LT4. This review seeks to provide an overview of currently available evidence on combination (LT4 + T3) therapy to be used for personalized medicine in patients with hypothyroidism. A number of randomized, controlled trials (RCTs) have failed to demonstrate superiority for the combination therapy approach, largely due to non-physiological T3 doses. However, patients with hypothyroidism are highly heterogeneous in terms of their residual thyroid function, individual set points for optimal thyroid homeostasis and for the presence or absence of polymorphisms in deiodinase enzymes in tissues that activate and deactivate circulating thyroid hormones. Accordingly, these RCTs may have failed to demonstrate benefits of combination therapy in individual hypothyroid phenotypes. The pharmacokinetics of LT4 and T3 also differ, which is a barrier to their co-administration. Future clinical trials using LT4 + T3 tablets better suited for combination therapy will resolve the outstanding research questions relating to the place of LT4 + T3 combination therapy in the management of hypothyroidism.
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The mean half-life (T1/2) is 7.5 days for T4 and 1.4 days for T3.
“The mean half-life (T1/2) is 7.5 days for T4 and 1.4 days for T3 (40, 41).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [41]
About 80% of circulating T3 comes from deiodination of T4, while the remaining 20% is released directly by the thyroid gland.
“Eighty percent of circulating T3 is derived from the deiodination of T4, and only the remaining 20% is directly released by the thyroid gland.22,25”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [25]
The average half-life of T4 is about 7.5 days, and that of T3 is about 1.4 days.
“The average half-life of T4 is approximately 7.5 days, while that of T3 is approximately 1.4 days.22,25”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [25]
The designs of these trials attracted criticism because they recruited relatively unselected populations with hypothyroidism, with no reason to believe that they might have benefitted specifically from T3 supplementation, such as those with polymorphisms of deiodinases that would predict low fT3.
“The designs of these trials attracted criticism, however, in that they recruited relatively unselected populations with hypothyroidism, with no reason to believe that they might have benefitted specifically from T3 supplementation, such as those with polymorphisms of deiodinases that would predict low fT3 3,5,23,27 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [3]
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References 65 · Cited by 9
- Authors
- Gottwald-Hostalek, U., & Kahaly, G. J.
- Affiliations
- Merck Healthcare KGaA, Darmstadt, Germany
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- ORCID
- Kahaly, George J.
- Venue
- Current Medical Research and Opinion
- Publisher
- Informa UK Limited
- Published
- 2021-10-12
- Volume
- 37
- Issue
- 12
- Pages
- 2099-2106
- ISSN
- 0300-7995 (ISSN-L)
- 1473-4877
- OpenAlex
- W3201305308
- Cited by
- 9
- References
- 65
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Medical Research and Opinion (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- 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, triiodothyronine, combination thyroid hormone therapy, personalized medicine, thyroid hormone replacement, thyroid-stimulating hormone, pharmacokinetics
- MeSH terms
- Humans, Hypothyroidism, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine
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