Hypothyroidism in patients with colorectal carcinoma treated with fluoropyrimidines

Fujiwara,Yutaka; Chayahara,Naoko; Mukohara,Toru; Kiyota,Naomi; Tomioka,Hideo; Funakoshi,Yohei; Minami,Hironobu

doi:10.3892/or.2013.2644

Hypothyroidism in patients with colorectal carcinoma treated with fluoropyrimidines

Authors:
- Yutaka Fujiwara
- Naoko Chayahara
- Toru Mukohara
- Naomi Kiyota
- Hideo Tomioka
- Yohei Funakoshi
- Hironobu Minami
View Affiliations

Affiliations: Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan, Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Kobe 650-0017, Japan
Published online on: July 30, 2013 https://doi.org/10.3892/or.2013.2644
Pages: 1802-1806

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Targeted therapy with tyrosine kinase inhibitors, including vascular endothelial growth factor receptors, has been demonstrated to induce hypothyroidism and thyroid dysfunction. Cancer patients with thyroid dysfunction may be underdiagnosed and undertreated. Thyroid function in colorectal cancer patients receiving fluoropyrimidine‑based chemotherapy with or without bevacizumab was evaluated at baseline and monthly. In the present study, 3 of 27 (11.1%) patients who received fluoropyrimidine‑based chemotherapy developed a thyroid-stimulating hormone (TSH) level >10 µU/ml, and 13 (48.1%) developed an elevation above the upper limit of the normal range. No difference in TSH elevation was noted between the bevacizumab and chemotherapy-alone group (50 vs. 45%; P=1.00, respectively). Three (11.1%) patients developed a TSH level >10 µU/ml and 2 with hypothyroidism were treated with thyroid hormone replacement therapy. We demonstrated that bevacizumab does not affect thyroid function but fluoropyrimidines may induce thyroid dysfunction in patients with colorectal cancer. Further investigation is required to clarify the mechanism of fluoropyrimidine-induced thyroid dysfunction.

View Figures

View References

1	Feldt S, Schüssel K, Quinzler R, et al: Incidence of thyroid hormone therapy in patients treated with sunitinib or sorafenib: a cohort study. Eur J Cancer. 48:974–981. 2012. View Article : Google Scholar : PubMed/NCBI
2	Torino F, Corsello SM, Longo R, Barnabei A and Gasparini G: Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol. 6:219–228. 2009. View Article : Google Scholar : PubMed/NCBI
3	Desai J, Yassa L, Marqusee E, et al: Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 145:660–664. 2006. View Article : Google Scholar : PubMed/NCBI
4	Rini BI, Tamaskar I, Shaheen P, et al: Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 99:81–83. 2007. View Article : Google Scholar : PubMed/NCBI
5	Wong E, Rosen LS, Mulay M, et al: Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid. 17:351–355. 2007. View Article : Google Scholar : PubMed/NCBI
6	Faris JE, Moore AF and Daniels GH: Sunitinib (Sutent)-induced thyrotoxicosis due to destructive thyroiditis: a case report. Thyroid. 17:1147–1149. 2007. View Article : Google Scholar : PubMed/NCBI
7	Abdulrahman RM, Verloop H, Hoftijzer H, et al: Sorafenib- induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab. 95:3758–3762. 2010. View Article : Google Scholar : PubMed/NCBI
8	Tamaskar I, Bukowski R, Elson P, et al: Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib. Ann Oncol. 19:265–268. 2008. View Article : Google Scholar : PubMed/NCBI
9	de Groot JW, Zonnenberg BA, Plukker JT, van Der Graaf WT and Links TP: Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther. 78:433–438. 2005.PubMed/NCBI
10	de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, et al: A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab. 92:3466–3469. 2007.PubMed/NCBI
11	Hollowell JG, Staehling NW, Flanders WD, et al: Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 87:489–499. 2002. View Article : Google Scholar
12	Eisen T, Sternberg CN, Robert C, et al: Targeted therapies for renal cell carcinoma: review of adverse event management strategies. J Natl Cancer Inst. 104:93–113. 2012. View Article : Google Scholar : PubMed/NCBI
13	Iavarone M, Perrino M, Viganò M, Beck-Peccoz P and Fugazzola L: Sorafenib-induced destructive thyroiditis. Thyroid. 20:1043–1044. 2010. View Article : Google Scholar
14	Kappers MH, van Esch JH, Smedts FM, et al: Sunitinib-induced hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary regression. J Clin Endocrinol Metab. 96:3087–3094. 2011. View Article : Google Scholar : PubMed/NCBI
15	Shinohara N, Takahashi M, Kamishima T, et al: The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma. Br J Cancer. 104:241–247. 2011. View Article : Google Scholar : PubMed/NCBI
16	Kim S, Yazici YD, Calzada G, et al: Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther. 6:1785–1792. 2007. View Article : Google Scholar : PubMed/NCBI
17	Saltz LB, Clarke S, Díaz-Rubio E, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 26:2013–2019. 2008. View Article : Google Scholar : PubMed/NCBI
18	Sandler A: Bevacizumab in non-small cell lung cancer. Clin Cancer Res. 13:s4613–s4616. 2007. View Article : Google Scholar : PubMed/NCBI
19	Miller K, Wang M, Gralow J, et al: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 357:2666–2676. 2007. View Article : Google Scholar : PubMed/NCBI
20	Van Meter ME and Kim ES: Bevacizumab: current updates in treatment. Curr Opin Oncol. 22:586–591. 2010.PubMed/NCBI
21	Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar : PubMed/NCBI
22	Cooper DS: Clinical practice. Subclinical hypothyroidism. N Engl J Med. 345:260–265. 2001. View Article : Google Scholar : PubMed/NCBI
23	Beex L, Ross A, Smals A and Kloppenborg P: 5-fluorouracil-induced increase of total serum thyroxine and triiodothyronine. Cancer Treat Rep. 61:1291–1295. 1977.PubMed/NCBI
24	Kamba T and McDonald DM: Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 96:1788–1795. 2007. View Article : Google Scholar : PubMed/NCBI
25	Wang JF, Milosveski V, Schramek C, Fong GH, Becks GP and Hill DJ: Presence and possible role of vascular endothelial growth factor in thyroid cell growth and function. J Endocrinol. 157:5–12. 1998. View Article : Google Scholar : PubMed/NCBI
26	Gordon MS, Margolin K, Talpaz M, et al: Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 19:843–850. 2001.PubMed/NCBI