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

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.

• 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
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 20 Issue 11 Pg. 1209-14 (Nov 2010) ISSN: 1557-9077 [Electronic] United States
• PMID: 20929406 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• Imatinib Mesylate
• nilotinib
• Dasatinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzamides
• Dasatinib
• Female
• Humans
• Imatinib Mesylate
• 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)