Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs
Open accessAbstract
Background: Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease. Summary: Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone–binding proteins without clinically relevant thyroid dysfunction. Old immunomodulating drugs, such as interferon-α and interleukin-2, are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for a relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Central hypothyroidism is a well-recognized side effect of bexarotene. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also increase the levothyroxine requirement in thyroidectomized patients. Conclusions: The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others it remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal thyrotropin following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well-powered prospective clinical trials.
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Accelerated conversion of T3 to rT3 due to D3 activation has been suggested as one mechanism by which tyrosine kinase inhibitors increase LT4 requirement in hypothyroid patients.
“Accelerated conversion of T3 to rT3 because of activation of D3 has been suggested to be one of the mechanisms by which tyrosine kinase inhibitors increase the LT4 requirement in hypothyroid patients (190,191).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [191]
The Tyrosine Kinase Inhibitors section (p. 7) says that TKIs may increase LT4 requirements in thyroidectomized hypothyroid patients and suggests increased DIO3 activity as a mechanism for some TKIs. It also reports decreased T3/rT3 ratios, but does not say that DIO3 accelerates conversion of T3 to rT3; that specific step is unsupported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe activity of other deiodinases may also be affected by tyrosine kinase inhibitors.
“The activity of other deiodinases may also be affected by these agents (191).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [191]
Nilotinib and dasatanib rarely alter L-T4 requirements.
“Nilotinib and dasatanib rarely alter L-T4 requirements (27).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [27]
Autoimmune thyroiditis is caused by monoclonal antibodies to programmed cell death-1 receptor (nivolumab and pembrolizumab) and to cytotoxic T lymphocyte-associated antigen-4 (ipilimumab, tremelimumab).
“Autoimmune thyroiditis is also caused by monoclonal Ab to programmed cell death-1 receptor (nivolumab and pembrolizumab), and Ab to cytotoxic T lymphocyte-associated antigen-4 (ipilimumab, tremelimumab) (27, 37–39).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [27]
Tyrosine kinase inhibitors may cause de novo hyperthyroidism or hypothyroidism, or worsen pre-existing hypothyroidism and increase L-T4 requirements.
“Tyrosine kinase inhibitors (TKI) may cause de novo hyperthyroidism or hypothyroidism, or worsen pre-existing hypothyroidism and increase L-T4 requirements (27–29).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [27]
Anti-CTLA-4 antibodies and anti-PD-1 antibodies induce autoimmune hypophysitis, with rates of 0-17.4% for ipilimumab, 0-2.6% for tremelimumab, 0-0.9% for nivolumab, and 0-1.2% for pembrolizumab.
“Anti-CTLA-4 Ab and anti-PD-1 Ab induce autoimmune hypophysitis (27, 37–39), with rates of 0–17.4% (ipilimumab), 0–2.6% (tremelimumab), 0–0.9% (nivolumab), and 0–1.2% (pembrolizumab) (38).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [27]
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References 240 · Cited by 117
- Authors
- Torino, F., Barnabei, A., Paragliola, R., Baldelli, R., Appetecchia, M., & Corsello, S. M.
- Affiliations
- University of Rome Tor Vergata (IT)
- Instituto Nazionale Tumori Regina Elena (IT)
- Università Cattolica
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Corsello, Salvatore Maria
- ORCID
- Venue
- Thyroid®
- Publisher
- SAGE Publications
- Published
- 2013-11
- Volume
- 23
- Issue
- 11
- Pages
- 1345-1366
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2168718152
- Cited by
- 117
- References
- 240
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 16 · 2019: 5 · 2018: 13 · 2017: 9 · 2016: 15 · 2015: 9 · 2014: 8
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
- 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
- drug-induced thyroid dysfunction, anticancer agents, tyrosine kinase inhibitors, immune checkpoint inhibitors, CTLA-4 blockade, bexarotene, central hypothyroidism, hypophysitis, thyroiditis, autoimmune thyroid disease, interferon-alpha, interleukin-2, thyroid hormone binding proteins, cytotoxic chemotherapy, thyroid hormone replacement
- MeSH terms
- Alemtuzumab, Lenalidomide, Bexarotene, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Diphtheria Toxin, Humans, Hypothyroidism, Interleukin-2, Neoplasms, Recombinant Fusion Proteins, Tetrahydronaphthalenes, Thalidomide, Thyroid Diseases, Thyroid Gland, Thyroid Hormones, Thyroxine, Interferon-alpha, Antibodies, Monoclonal, Humanized
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