Document Detail


Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia.
MedLine Citation:
PMID:  20929406     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Theo D Kim; Michaela Schwarz; Hendrik Nogai; Peggy Grille; Jörg Westermann; Ursula Plöckinger; Doreen Braun; Ulrich Schweizer; Renate Arnold; Bernd Dörken; Philipp le Coutre
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Publication Detail:
Type:  Journal Article     Date:  2010-10-07
Journal Detail:
Title:  Thyroid : official journal of the American Thyroid Association     Volume:  20     ISSN:  1557-9077     ISO Abbreviation:  Thyroid     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-10     Completed Date:  2011-03-07     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9104317     Medline TA:  Thyroid     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1209-14     Citation Subset:  IM    
Affiliation:
Clinic for Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany. theo.kim@charite.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents / adverse effects*,  therapeutic use
Female
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics
Male
Middle Aged
Philadelphia Chromosome*
Piperazines / adverse effects,  therapeutic use*
Protein Kinase Inhibitors / adverse effects*,  therapeutic use
Pyrimidines / adverse effects*,  therapeutic use*
Retrospective Studies
Thiazoles / adverse effects*,  therapeutic use
Thyroid Diseases / chemically induced*,  diagnosis
Thyroid Function Tests
Thyroid Gland / drug effects*
Chemical
Reg. No./Substance:
0/4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0/Antineoplastic Agents; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/Thiazoles; BKJ8M8G5HI/imatinib; RBZ1571X5H/dasatinib

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