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Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality

Planck, Tereza LU ; Hedberg, Fredric ; Calissendorff, Jan and Nilsson, Anton LU (2021) In Thyroid 31(5). p.732-739
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... (More)

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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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, cancer, hypothyroidism, levothyroxine, liothyronine, mortality, triiodothyronine
in
Thyroid
volume
31
issue
5
pages
8 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:85105721155
  • pmid:33040688
ISSN
1050-7256
DOI
10.1089/thy.2020.0388
language
English
LU publication?
yes
additional info
Funding Information: This work was supported by grants from Lundgrens Stif-telse and SUS fonder. Publisher Copyright: © 2021, Mary Ann Liebert, Inc., publishers. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
a023f3f4-aded-4434-8964-e3911bb8fc73
date added to LUP
2021-06-03 14:47:53
date last changed
2024-07-13 14:28:50
@article{a023f3f4-aded-4434-8964-e3911bb8fc73,
  abstract     = {{<p>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.</p>}},
  author       = {{Planck, Tereza and Hedberg, Fredric and Calissendorff, Jan and Nilsson, Anton}},
  issn         = {{1050-7256}},
  keywords     = {{breast cancer; cancer; hypothyroidism; levothyroxine; liothyronine; mortality; triiodothyronine}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{732--739}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Thyroid}},
  title        = {{Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality}},
  url          = {{http://dx.doi.org/10.1089/thy.2020.0388}},
  doi          = {{10.1089/thy.2020.0388}},
  volume       = {{31}},
  year         = {{2021}},
}