Background: Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic... Show moreBackground: Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism. Aim: The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients. Design: The design included a prospective open, single-center, single-arm 26-wk study. Methods: We measured serum thyroxine (T-4), free T-4, 3,5,3-triiodothyronine (T-3), free T-3, reverse T-3 (rT(3)), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive non-medullary thyroid carcinoma treated with sorafenib. Ratios of T-3/T-4 and T-3/rT(3), which are independent of substrate availability and reflect iodothyronine deiodination, were calculated. Results: Serum free T-4 and T-3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T-3/T-4 and T-3/rT(3) ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination. Conclusions: Sorafenib enhances T-4 and T-3 metabolism, which is probably caused by increased type 3 deiodination. (J Clin Endocrinol Metab 95: 3758-3762, 2010) Show less
Background: Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic... Show moreBackground: Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism. Aim: The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients. Design: The design included a prospective open, single-center, single-arm 26-wk study. Methods: We measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive nonmedullary thyroid carcinoma treated with sorafenib. Ratios of T3/T4 and T3/rT3, which are independent of substrate availability and reflect iodothyronine deiodination, were calculated. Results: Serum free T4 and T3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T3/T4 and T3/rT3 ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination. Conclusions: Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination. Show less
To compare disease-specific survival and recurrence-free survival (RFS) after successful I-131 ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation... Show moreTo compare disease-specific survival and recurrence-free survival (RFS) after successful I-131 ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1 +/- 4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. After a mean follow-up of 81 +/- 64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged a parts per thousand currency sign45 years those aged > 45 years at diagnosis (p=0.018). After (near) total thyroidectomy and successful I-131 ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. Show less
