Int J Thyroidol.  2018 Nov;11(2):88-91. 10.11106/ijt.2018.11.2.88.

A Case Report of Severe Hypocalcemia and Hypothyroidism after Tyrosine Kinase Inhibitor Treatment

Affiliations
  • 1Division of Endocrinology, Center for Thyroid Cancer, National Cancer Center, Goyang, Korea. waterfol@ncc.re.kr

Abstract

After introducing tyrosine kinase inhibitors (TKIs) as promising treatments for radioactive iodine refractory advanced thyroid cancer patients, we more often meet patients with TKI-related hormone and electrolyte imbalances in clinics. Hypocalcemia associated with TKI is associated with an imbalance in calcium-vitamin D metabolism. TKI-related hypothyroidism is related to the metabolic rate of thyroid hormones. The two side effects usually occur in the early stages of TKI treatment, and if the imbalance is corrected appropriately, the effects are minor, but in severe cases, the TKI should be discontinued. The authors reported a case of severe hypocalcemia and thyroid dysfunction after TKI treatment. A 56-year-old man suffered from symptomatic hypocalcemia during TKI treatment, which was resolved after he stopped taking the TKI medication. Although calcium and vitamin D replacement have increased, hypocalcemia was recurred and TKI treatments have been permanently stopped due to serious weight loss in grade 3. After the interruption, his calcium levels normalized.

Keyword

Tyrosine kinase inhibitor; Hypocalcemia; Hypothyroidism; Thyroid cancer; Adverse event

MeSH Terms

Calcium
Humans
Hypocalcemia*
Hypothyroidism*
Iodine
Metabolism
Middle Aged
Protein-Tyrosine Kinases*
Thyroid Gland
Thyroid Hormones
Thyroid Neoplasms
Tyrosine*
Vitamin D
Weight Loss
Calcium
Iodine
Protein-Tyrosine Kinases
Thyroid Hormones
Tyrosine
Vitamin D

Reference

1. Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015; 372(7):621–630.
Article
2. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014; 384(9940):319–328.
Article
3. Kawalec P, Malinowska-Lipien I, Brzostek T, Kozka M. Lenvatinib for the treatment of radioiodine-refractory differentiated thyroid carcinoma: a systematic review and indirect comparison with sorafenib. Expert Rev Anticancer Ther. 2016; 16(12):1303–1309.
Article
4. Yi KH, Lee EK, Kang HC, Koh Y, Kim SW, Kim IJ, et al. 2016 Revised Korean Thyroid Association Management Guidelines for patients with thyroid nodules and thyroid cancer. Int J Thyroidol. 2016; 9(2):59–126.
Article
5. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016; 26(1):1–133.
Article
6. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015; 16(15):1473–1482.
Article
7. Dy GK, Adjei AA. Understanding, recognizing, and managing toxicities of targeted anticancer therapies. CA Cancer J Clin. 2013; 63(4):249–279.
Article
8. Puzziello A, Rosato L, Innaro N, Orlando G, Avenia N, Perigli G, et al. Hypocalcemia following thyroid surgery: incidence and risk factors. A longitudinal multicenter study comprising 2,631 patients. Endocrine. 2014; 47(2):537–542.
Article
9. Seong JY, Lee CR, Kim MJ, Kim TH, Lee SG, Choi JB, et al. Risk factors of postoperative hypocalcemia after total thyroidectomy of papillary thyroid carcinoma patients. Korean J Endocr Surg. 2016; 16(3):70–78.
Article
10. Eismontas V, Slepavicius A, Janusonis V, Zeromskas P, Beisa V, Strupas K, et al. Predictors of postoperative hypocalcemia occurring after a total thyroidectomy: results of prospective multicenter study. BMC Surg. 2018; 18(1):55.
Article
11. Roh JL, Park JY, Park CI. Prevention of postoperative hypocalcemia with routine oral calcium and vitamin D supplements in patients with differentiated papillary thyroid carcinoma undergoing total thyroidectomy plus central neck dissection. Cancer. 2009; 115(2):251–258.
Article
12. Bellini E, Pia A, Brizzi MP, Tampellini M, Torta M, Terzolo M, et al. Sorafenib may induce hypophosphatemia through a fibroblast growth factor-23 (FGF23)-independent mechanism. Ann Oncol. 2011; 22(4):988–990.
Article
13. Mir O, Coriat R, Boudou-Rouquette P, Durand JP, Goldwasser F. Sorafenib-induced diarrhea and hypophosphatemia: mechanisms and therapeutic implications. Ann Oncol. 2012; 23(1):280–281.
Article
14. Phillip V, Zahel T, Bartl K, Rasch S, Ebert O, Schmid RM, et al. Influence of Sorafenib and Bevacizumab on pancreatic volume - A monocentric CT based analysis. Pancreatology. 2016; 16(4):621–624.
Article
15. Porta C, Cosmai L, Gallieni M, Pedrazzoli P, Malberti F. Renal effects of targeted anticancer therapies. Nat Rev Nephrol. 2015; 11(6):354–370.
Article
16. Deininger MW, O'Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol. 2003; 21(8):1637–1647.
Article
17. Worden F, Fassnacht M, Shi Y, Hadjieva T, Bonichon F, Gao M, et al. Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. Endocr Relat Cancer. 2015; 22(6):877–887.
Article
18. Wong E, Rosen LS, Mulay M, Vanvugt A, Dinolfo M, Tomoda C, et al. Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid. 2007; 17(4):351–355.
Article
19. Abdulrahman RM, Verloop H, Hoftijzer H, Verburg E, Hovens GC, Corssmit EP, et al. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab. 2010; 95(8):3758–3762.
Article
20. Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006; 290(2):H560–H576.
Article
21. Jean GW, Mani RM, Jaffry A, Khan SA. Toxic effects of sorafenib in patients with differentiated thyroid carcinoma compared with other cancers. JAMA Oncol. 2016; 2(4):529–534.
Article
22. Verloop H, Smit JW, Dekkers OM. Sorafenib therapy decreases the clearance of thyrotropin. Eur J Endocrinol. 2013; 168(2):163–167.
Article
23. Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, et al. Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer. 2011; 117(3):534–544.
Article
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