Hypothyroidism related to tyrosine kinase inhibitors: an underdiagnosed disorder?
Teresa Azevedo, Mariana Martinho, Teresa Martins, Florbela Dias, Nuno Cunha, Frederico Valido, Helena Gervásio & Fernando Rodrigues
Introduction: Tyrosine Kinase Inhibitors (TKIs) are approved for the treatment of several cancers and can induce hypothyroidism by unclarified mechanisms.
Objectives: To assess the prevalence of hypothyroidism in patients treated with TKIs.
Methods: Retrospective review of clinical records of patients treated with TKIs in our institution between 2003 and 2009. We evaluated parameters such as sex, oncologic pathology, TKI used, TSH and free T4, dose of levothyroxine.
Results: We evaluated 37 patients, 20 were men (54%) and 17 women (46%). Imatinib was used in 24 patients, sunitinib in 11, lopatinib in 1 and sorafenib in another. Twenty-one patients (56.8%) had gastrointestinal stromal tumour, 8 (21.6%) chronic myeloid leukaemia, 6 (16.2%) renal cell carcinoma, 1 (2.7%) breast cancer and 1 (2.7%) hepatocellular carcinoma. Thyroid function tests (TFT) were assessed prior to treatment with TKI in 6 patients (all euthyroid) and during or after treatment with TKI in 13 patients (35.1%). Of these 13 patients, 6 were hypothyroid (46.2%) after a mean period of 12.2±5.2 months of TKI therapy. Thyroid function was not evaluated in 24 of 37 patients (64.9%). Only 3 out of 24 patients treated with imatinib were screened for thyroid dysfunction and all were euthyroid. TFT were assessed in 8 of the 11 patients treated with sunitinib, 5 of which were hypothyroid (62.5%). The patient treated with sorafenib was euthyroid and the one treated with lopatinib had hypothyroidism.
Conclusion: A high percentage of patients was not screened for thyroid dysfunction. The prevalence of hypothyroidism in the patients who performed TFT was 46.2%. Sunitinib seems to induce hypothyroidism more frequently. It is important to consider this TKI adverse effect and include TFT in routine toxicity assessment of these patients.