Subclinical Hypothyroidism Following Imatinib Use in Nigerian BCR::ABL1-positive Chronic Myeloid Leukemia Patients: A Prospective Cohort Study

Abstract

Background: Thyroid toxicity has been reported with tyrosine kinase inhibitors (TKIs) such as sunitinib and sorafenib, targeting angiogenic tyrosine kinase receptors. However, the effect of imatinib, a first-line TKI for chronic myeloid leukemia (CML) patients on the thyroid, has been inconclusive. Of note, imatinib remains the mainstay of treatment for BCR::ABL1-positive Nigerian CML patients. AIM: We evaluated the effect of imatinib mesylate on the thyroid and its function in BCR::ABL1 positive CML patients and assessed the effect of the continuous imatinib use on thyroid features. PATIENTS AND METHODS: This prospective cohort study included 50 imatinib-naive patients with BCR::ABL1-positive CML and 50 age- and sex-matched apparently normal controls without any underlying thyroid disorder or on any thyroid medication. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were measured at baseline for both the CML patients and the controls and were repeated at 1, 3, and 6 months for the CML patients while on imatinib therapy. Results: Subclinical hypothyroidism was observed in 7 of 50 (14%) of the patients with CML at 6 months on imatinib. Six of these patients were female, while 1 was male. The mean values for the serum fT3 (pmol/L), serum fT4 (pmol/L), and TSH (μIU/mL) for the CML subjects versus controls were 4.22 ± 0.79 versus 4.31 ± 0.31 (t = −0.27 P = 0.532), 17.13 ± 2.49 vs. 16.39 ± 2.16 (t = 1.605 P = 0.112), and 1.58 ± 0.74 versus 1.63 ± 0.64 (t = −0.399 P = 0.691), respectively. Conclusion: This study confirmed subclinical hypothyroidism as an adverse effect of continuous imatinib use with a prevalence of 14% in Nigerian CML patients.

Keywords

• bcr::abl1
• chronic myeloid leukemia
• imatinib mesylate
• subclinical hypothyroidism