Imatinib induces hypothyroidism in patients receiving levothyroxine
Abstract
Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% +/- 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri-iodothyronine (fT3) values remained within the reference range (59% +/- 17% of the upper limit for fT4 and 63% +/- 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism.
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A substantially increased LT4 dose has been reported in athyreotic patients prescribed tyrosine kinase inhibitors such as imatinib, motesanib, sorafenib, sunitinib, and vandetanib.
“The need for a substantially increased dose of LT4 has been reported in athyreotic patients prescribed tyrosine kinase inhibitors such as imatinib (188), motesanib (189), sorafenib (190), sunitinib, and vandetanib (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 [188]
Phenytoin and imatinib inactivate LT4 via nondeiodinative hepatic metabolism and decrease the ratio of T3 to T4.
“Similarly, phenytoin and imatinib inactivate LT4 via nondeiodinative hepatic metabolism and decrease the ratio of T3 to T4 (89, 90).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [89]
A number of kinase inhibitors, including imatinib and sunitinib, appear to influence thyroxine requirements through what is likely a class effect.
“A number of kinase inhibitors, including imatinib and sunitinib, appear to influence thyroxine requirements through what is likely a class effect [114–116].”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [114]
Upgraded titration of L-T4 was reported in athyreotic patients prescribed imatinib, motesanib, sorafenib, sunitinib, and vandetanib.
“Upgraded titration of L-T4 was reported in athyreotic patients prescribed imatinib, motesanib, sorafenib, sunitinib, and vandetanib (5, 62, 63).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [63]
Thyroid dysfunction is a well-known adverse effect of TKIs in euthyroid individuals and may increase the requirement for LT4 in individuals with hypothyroidism.
“More generally, thyroid dysfunction is a well-known adverse effect of TKIs in euthyroid individuals – although not necessarily by modifying the metabolism of LT4 –and so may increase the requirement for LT4 in individuals with hypothyroidism [ 114 , 115 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [115]
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References 24 · Cited by 159
- Authors
- DEGROOT, J., ZONNENBERG, B., PLUKKER, J., VANDERGRAAF, W., & LINKS, T.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- LINKS, T
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2005-10
- Volume
- 78
- Issue
- 4
- Pages
- 433-438
- ISSN
- 0009-9236 (ISSN-L)
- OpenAlex
- W1965914891
- Cited by
- 159
- References
- 24
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 14 · 2012: 9
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- 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
- imatinib, levothyroxine, drug interactions, hypothyroidism, thyroid-stimulating hormone, thyroidectomy, medullary thyroid carcinoma, gastrointestinal stromal tumor, free thyroxine, free triiodothyronine, thyroid hormone replacement
- MeSH terms
- Imatinib Mesylate, Adult, Aged, Antineoplastic Agents, Benzamides, Drug Synergism, Female, Humans, Hypothyroidism, Male, Middle Aged, Piperazines, Pyrimidines, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Thyroxine, Triiodothyronine, Carcinoma, Medullary, Gastrointestinal Stromal Tumors
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