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Cited by 35Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentThyroid and Parathyroid Surgery

Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality

Planck, Tereza, Hedberg, Fredric, Calissendorff, Jan, Nilsson, Anton·2021·Thyroid®
DOI 10.1089/thy.2020.0388
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Abstract

Background: The prescription of liothyronine (LT3) to treat hypothyroidism is increasing worldwide; however, the long-term safety of LT3 use has yet to be determined. Previous studies have suggested a possible association between LT3 use and breast cancer. The aim of this study was to examine the effects of LT3 use on cancer incidence and mortality. Methods: Our sample included the full adult population of individuals living in Sweden with at least three purchases of thyroid hormone therapy between July 2005 and December 2017. Individual-level data on drug purchases were linked to registry data on cancer incidence and mortality. There were 575,461 individuals with at least three purchases, of which 11,147 had made at least three purchases of LT3, including combinations of levothyroxine (LT4) and LT3. Individuals were followed for a median follow-up time of 8.1 years. We applied Cox regression with a time-varying exposure variable, comparing LT3 users (individuals with at least three cumulative purchases of LT3) with LT4-only users (the rest). Outcomes included breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, and breast cancer mortality. We adjusted for age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose in multivariate analyses. Results: Multivariate analyses produced a hazard ratio of 0.93 (95% confidence interval [0.75–1.15]) for breast cancer incidence (only females), 0.97 (0.87–1.08) for any cancer incidence, 0.69 (0.61–0.77) for all-cause mortality, 0.78 (0.62–0.98) for any cancer mortality, and 0.91 (0.50–1.66) for breast cancer mortality (only females). Conclusions: In this large, Swedish, long-term registry-based study, the use of LT3 did not lead to increased breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality compared with LT4 use. Somewhat surprisingly, there was evidence of lower mortality in LT3 users in models adjusting for dose, potentially an artifact of underlying associations between dose and health status/diagnosis.

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Crossref · 10.1089/thy.2020.0388

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  • The use of LT3 did not lead to increased breast cancer or any cancer incidence and mortality compared with LT4 use.

    “The use of LT3 did not lead to increased breast cancer or any cancer incidence and mortality compared with LT4 use [89].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [89]

  • Neither the Korean study nor another Swedish study have been able to confirm an association of breast or other cancers, or all-cause mortality with the use of liothyronine.

    “Neither this Korean study, nor another Swedish study have been able to confirm an association of breast or other cancers, or all -cause mortality with the use of liothyronine. 70,71”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [71]

  • Pooled mortality data from 2 large studies showed a statistically significant reduction in all-cause mortality among LT3 users compared with LT4 users.

    “Notably, pooled mortality data from 2 large studies showed a statistically significant reduction in all-cause mortality among LT3 users compared with LT4 users.”

    From Risk of Death and Adverse Effects in Patients on Liothyronine: A Multisource Systematic Review and Meta-analysis (2025) · cites this paper as [78]

  • Similar findings were obtained in Sweden after all-cause mortality was compared between 500,000 patients taking LT4 and 11,000 patients on therapy containing LT3.

    “Similar findings were obtained in Sweden after all-cause mortality was compared between 500,000 patients taking LT4 and 11,000 patients on therapy containing LT3 (52).”

    From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [52]

  • Multiple randomized controlled trials and large retrospective studies show that therapy containing T3 is as safe as therapy with LT4.

    “While the multiple RCTs and large retrospective studies show that therapy containing T3 is as safe as therapy with LT4, the 2014 American Thyroid Association clinical guidelines for the treatment of hypothyroidism called for the development of new T3 formulations that would avoid the swings in serum T3 levels observed with the current T3-containing formulations, i.e., LT3 or DTE.”

    From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [52]

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Authors
Planck, T., Hedberg, F., Calissendorff, J., & Nilsson, A.
Affiliations
  • Lund University (SE)
  • Karolinska University Hospital (SE)
Corresponding author
Planck, Tereza
ORCID
Venue
Thyroid®
Publisher
SAGE Publications
Published
2021-05
Volume
31
Issue
5
Pages
732-739
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2020.0388
OpenAlex
W3092543117
Cited by
35
References
39
Citations by year
2026: 3 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 1
FWCI
4.53
Type
journal article
Language
en
Open access
closed
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Thyroid (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
liothyronine, levothyroxine, hypothyroidism, thyroid hormone replacement, breast cancer incidence, cancer mortality, all-cause mortality, drug safety, levothyroxine dose, drug purchases
MeSH terms
Adult, Breast Neoplasms, Cause of Death, Drug Therapy, Combination, Female, Humans, Hypothyroidism, Male, Middle Aged, Mortality, Neoplasms, Risk Factors, Thyroxine, Triiodothyronine, Multivariate Analysis, Proportional Hazards Models

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