Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia

Kim, T.D.; Schwarz, M.; Nogai, H.; Grille, P.; Westermann, J.; Ploeckinger, U.; Braun, D.; Schweizer, U.; Arnold, R.; Doerken, B.; le Coutre, P.

Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia

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Item Type:	Article
Title:	Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia
Creators Name:	Kim, T.D., Schwarz, M., Nogai, H., Grille, P., Westermann, J., Ploeckinger, U., Braun, D., Schweizer, U., Arnold, R., Doerken, B. and le Coutre, P.
Abstract:	BACKGROUND: Thyroid dysfunction is a well-known adverse effect of first-generation tyrosine kinase inhibitors (TKIs), like sunitinib. The aim of this study was to investigate the effect of second-generation TKIs on thyroid function. METHODS: We retrospectively assessed the effect of the first-generation TKI imatinib and the second-generation TKI nilotinib and dasatinib on thyroid function tests in 73 Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia patients. RESULTS: Overall, 33 of 73 (45%) had one or more thyroid function test abnormalities during follow-up. Hypothyroidism or hyperthyroidism were found in 18 of 73 (25%) and 21 of 73 (29%) cases after a median of 6 and 22 weeks, respectively. In most patients (29 of 39, 74%) thyroid dysfunction was transient without clinical symptoms. Therapy of hypo-/hyperthyroidism was required in three patients. Thyroid dysfunction never resulted in the discontinuation of TKI therapy. Under treatment with imatinib, nilotinib, and dasatinib, thyroid abnormalities were detected in 25%, 55%, and 70%, respectively. Four of 55 patients (7%) treated with nilotinib had evidence for an autoimmune thyroiditis (antibody positive in 3 of 4 patients) with an episode of hyperthyroidism preceding hypothyroidism. CONCLUSIONS: Thyroid dysfunction is a common adverse event with second-generation TKI therapy in patients with Ph-positive chronic myeloid leukemia. Although the mechanism is still unclear, the high frequency of thyroid abnormalities, including autoimmune thyroiditis, warrants regular and long-term monitoring of thyroid function in these patients.
Keywords:	Antineoplastic Agents, BCR-ABL Positive Chronic Myelogenous Leukemia, Philadelphia Chromosome, Piperazines, Protein Kinase Inhibitors, Pyrimidines, Retrospective Studies, Thiazoles, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland
Source:	Thyroid
ISSN:	1050-7256
Publisher:	Mary Ann Liebert
Volume:	20
Number:	11
Page Range:	1209-1214
Date:	9 November 2010
Official Publication:	https://doi.org/10.1089/thy.2010.0251
PubMed:	View item in PubMed

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