Clinical Profile of Non-thyroidal Cancer Patients with Tyrosine Kinase Inhibitor-Induced Thyroid Dysfunction in the University of Santo Tomas Hospital, Philippines
A 5-Year Single-Center Retrospective Study
DOI:
https://doi.org/10.15605/jafes.039.02.14Keywords:
tyrosine kinase inhibitors, hypothyroidism, hyperthyroidismAbstract
Objectives. This study aimed to determine the clinical profile of non-thyroidal cancer patients with thyroid dysfunction associated with tyrosine kinase inhibitor (TKI) therapy at the University of Santo Tomas Hospital (USTH), Philippines.
Methodology. This is a retrospective observational study of TKI-initiated adult non-thyroidal cancer patients with thyroid function testing from 2013 to 2018.
Results. Forty percent (95% CI: 26.2% - 58.61%) of the sixty individuals who had thyroid function tests (TFT) had incident thyroid dysfunction. Thirty percent had hypothyroidism (i.e., 25% overt [mean TSH 16.64 uIU/mL]; 5% subclinical [mean TSH 6.62 uIU/mL]). The median time at risk was 8 and 16 months for overt and subclinical hypothyroidism, respectively. Fifty-six percent had persistent hypothyroidism (median TSH 16.75, p = 0.009). The average time to recovery of transient hypothyroidism was 39 months. Ten percent had hyperthyroidism with a median time at risk of 1.5 months. Non-small cell lung cancer and renal cell carcinoma were possible associated risk factors of thyroid dysfunction.
Conclusion. TKI-induced thyroid dysfunctions are common. Screening and monitoring for thyroid abnormalities during TKI therapy is important.
Downloads
References
1. Pottier C, Fresnais M, Gilon M, Jérusalem G, Longuespée R, Sounni NE. Tyrosine kinase inhibitors in cancer: Breakthrough and challenges of targeted therapy. Cancers (Basel). 2020;12(3):731. https://pubmed.ncbi.nlm.nih.gov/32244867 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140093 https://doi.org/10.3390/cancers12030731
2. Jannin A, Penel N, Ladsous M, Vantyghem MC, Do Cao C. Tyrosine kinase inhibitors and immune checkpoint inhibitors-induced thyroid disorders. Crit Rev Oncol Hematol. 2019;141:23-35. https://pubmed.ncbi.nlm.nih.gov/31202955 https://doi.org/10.1016/j.critrevonc.2019.05.015
3. Ahmadieh H, Salti I. Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment. Biomed Res Int. 2013; 2013:725410. https://pubmed.ncbi.nlm.nih.gov/24282820 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824811 https://doi.org/10.1155/2013/725410
4. Torino F, Corsello SM, Longo R, Barnabei A, Gasparini G. Hypothyroidism related to tyrosine kinase inhibitors: An emerging toxic effect of targeted therapy. Nat Rev Clin Oncol. 2009;6(4):219-28. https://pubmed.ncbi.nlm.nih.gov/19333228 https://doi.org/10.1038/nrclinonc.2009.4
5. Fallahi P, Ferrari SM, Vita R, et al. Thyroid dysfunctions induced by tyrosine kinase inhibitors. Expert Opin Drug Saf. 2014;13(6):723-33. https://pubmed.ncbi.nlm.nih.gov/24821006 https://doi.org/10.1517/14740338.2014.913021
6. Makita N, Iiri T. Tyrosine kinase inhibitor-induced thyroid disorders: A review and hypothesis. Thyroid. 2013;23(2):151-9. https://pubmed.ncbi.nlm.nih.gov/23398161 https://doi.org/10.1089/ thy.2012.0456
7. Lechner MG, Vyas CM, Hamnvik OPR, et al. Risk factors for new hypothyroidism during tyrosine kinase inhibitor therapy in advanced nonthyroidal cancer patients. Thyroid. 2018;28(4):437-44. https://pubmed.ncbi.nlm.nih.gov/29652599 https://doi.org/10.1089/thy.2017.0579
8. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061-8. https://pubmed.ncbi.nlm.nih.gov/20100962 https://doi.org/10.1200/JCO.2009.23.9764
9. Wolter P, McCann L, Sternberg CN, et al. Incidence of thyroid dysfunction in renal cell carcinoma (RCC) patients treated with pazopanib in prospective clinical trials. J Clin Oncol. 2011. 29:15:4633. https://doi.org/10.1200/jco.2011.29.15_suppl.4633
10. Kishikawa T, Kasai T, Okada M, et al. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor: A retrospective multicenter study of its real-world efficacy and safety in advanced/recurrent non-small cell lung carcinoma. Thorac Cancer. 2020;11(4):935-42. https://pubmed.ncbi.nlm.nih.gov/32129931 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113046 https://doi.org/10.1111/1759-7714.13378
11. Li S, Segal EM. Osimertinib: a novel therapeutic option for overcoming T790M mutations in non-small cell lung cancer. J Adv Pract Oncol. 2017;8(2):196-201. https://pubmed.ncbi.nlm.nih.gov/29900027 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995494 https://doi.org/10.6004/jadpro.2017.8.2.7
12. Soni S, Rastogi A, Prasad KT, Behera D, Singh N. Thyroid dysfunction in non-small cell lung cancer patients treated with epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors: Results of a prospective cohort. Lung Cancer. 2021;151:16-9. https://pubmed.ncbi.nlm.nih.gov/33278669 https://doi.org/10.1016/j.lungcan.2020.11.007
13. de Groot JWB, Zonnenberg BA, Plukker JT, van Der Graaf WTA, Links TP. Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther. 2005;78(4):433-8. https://pubmed.ncbi.nlm.nih.gov/16198662 https://doi.org/10.1016/j.clpt.2005.06.010
14. Komeno Y, Uchida N, Satoh Y, et al. Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report. Oncol Lett. 2017;13(6):4285-9. https://pubmed.ncbi.nlm.nih.gov/28599428 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452986 https://doi.org/10.3892/ol.2017.5989
15. Patel S, Nayernama A, Jones SC, de Claro RA, Waldron PE. BCR-ABL1 tyrosine kinase inhibitor-associated thyroid dysfunction: A review of cases reported to the FDA Adverse Event Reporting System and published in the literature. Am J Hematol. 2020;95(12):E332-35. https://pubmed.ncbi.nlm.nih.gov/32918288 https://doi.org/10.1002/ajh.25997
16. Mannavola D, Coco P, Vannucchi G, et.al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab. 2007;92(9):3531-4. https://pubmed.ncbi.nlm.nih.gov/17595247 https://doi.org/10.1210/jc.2007-0586
17. Wolter P, Stefan C, Decallonne B, Dumez H, Bex M, Carmeliet P, Schöffski P. The clinical implications of sunitinib-induced hypothyroidism: A prospective evaluation. Br J Cancer. 2008;99(3):448-54. https://pubmed.ncbi.nlm.nih.gov/18665181 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527784 https://doi.org/10.1038/sj.bjc.6604497
18. Clemons J, Gao D, Naam M, Breaker K, Garfield D, Flaig TW. Thyroid dysfunction in patients treated with sunitinib or sorafenib. Clin Genitourin Cancer. 2012;10(4):225-31. https://pubmed.ncbi.nlm.nih.gov/23017335 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511908 https://doi.org/10.1016/j.clgc.2012.08.002
19. Chawalitmongkol K, Maneenil K, Thungthong P, Deerochanawong C. Prevalence and associated factors for thyroid dysfunction among patients on targeted therapy for cancers: A single-center study from Thailand. J ASEAN Fed Endocr Soc. 2023;38(2):77–85. https://pubmed.ncbi.nlm.nih.gov/38045662 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692429 https://doi.org/10.15605/jafes.038.02.18
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Nenuel Angelo Luna, Jennilyn Quinitio, Erick Mendoza, Sjoberg Kho, Priscilla Caguioa
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Journal of the ASEAN Federation of Endocrine Societies is licensed under a Creative Commons Attribution-NonCommercial 4.0 International. (full license at this link: http://creativecommons.org/licenses/by-nc/3.0/legalcode).
To obtain permission to translate/reproduce or download articles or use images FOR COMMERCIAL REUSE/BUSINESS PURPOSES from the Journal of the ASEAN Federation of Endocrine Societies, kindly fill in the Permission Request for Use of Copyrighted Material and return as PDF file to jafes@asia.com or jafes.editor@gmail.com.
A written agreement shall be emailed to the requester should permission be granted.
