Impact of Tyrosine Kinase Inhibitors on Thyroid Function in Chronic Myeloid Leukemia: A Systematic Review

Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes in chronic myeloid leukemia (CML), shifting it from a fatal to a manageable chronic condition. Despite their clinical benefits, TKIs have been increasingly associated with endocrine-related adverse effects, most notably thyroid dysfunction. This systematic review explores the prevalence, clinical features, underlying mechanisms, and prognostic implications of TKI-induced thyroid abnormalities in CML patients. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across four databases, namely, PubMed, Excerpta Medica database (Embase), ClinicalKey, and Google Scholar, yielding 4,803 records. After applying inclusion and exclusion criteria and quality assessments using the Newcastle-Ottawa Scale (NOS) and A Measurement Tool to Assess Systematic Reviews (AMSTAR 2), eight studies (six observational studies and two systematic reviews) were included in the final analysis. Subclinical hypothyroidism emerged as the most frequently reported thyroid dysfunction, particularly associated with imatinib and second-generation TKIs such as nilotinib and dasatinib. Proposed mechanisms include destructive thyroiditis, reduced iodide uptake, regression of thyroid vasculature via vascular endothelial growth factor (VEGF) inhibition, inhibition of monocarboxylate transporter 8 (MCT8)-mediated thyroid hormone transport, and increased deiodinase activity leading to hormone inactivation. Notably, several studies identified an association between autoimmune thyroiditis and improved molecular response to TKIs, suggesting a potential role for thyroid autoimmunity as a biomarker of therapeutic efficacy. While most thyroid abnormalities were subclinical and did not necessitate treatment, overt hypothyroidism required thyroid hormone replacement and endocrine follow-up. This review emphasizes the importance of routine thyroid function monitoring during TKI treatment and highlights the potential prognostic implications of thyroid autoimmunity. Future large-scale, prospective studies are needed to establish standardized monitoring protocols and clarify the clinical significance of thyroid changes in optimizing CML management.