Department of Endocrinology, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
J Clin Endocrinol Metab. 2010 Aug;95(8):3758-62. doi: 10.1210/jc.2009-2507. Epub 2010 May 19.
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.
The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients.
The design included a prospective open, single-center, single-arm 26-wk study.
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.
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.
Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination.
酪氨酸激酶抑制剂治疗与甲状腺功能障碍相关。甲状腺癌无甲状腺功能患者在接受酪氨酸激酶抑制剂治疗期间，其血清甲状腺激素水平也会降低。因此，我们假设酪氨酸激酶抑制剂可能会影响甲状腺激素代谢。
本研究旨在探讨索拉非尼治疗对无甲状腺功能的甲状腺癌患者血清甲状腺激素浓度和碘甲状腺原氨酸脱碘的影响。
这是一项前瞻性开放、单中心、单臂 26 周研究。
我们在 21 例接受索拉非尼治疗的进展性非髓样甲状腺癌患者中，分别于基线和 26 周时测量血清甲状腺素（T4）、游离 T4、三碘甲状腺原氨酸（T3）、游离 T3、反 T3（rT3）和 TSH 浓度。T3/T4 和 T3/rT3 比值，这两个比值不受底物可用性的影响，反映了碘甲状腺原氨酸脱碘，也在治疗前后进行了计算。
按每公斤体重给予左甲状腺素剂量校正后，血清游离 T4 和 T3 水平分别下降了 11%和 18%，而 TSH 水平升高。血清 T3/T4 和 T3/rT3 比值分别下降了 18%和 22%，这与 3 型脱碘增加相一致。
索拉非尼增强了 T4 和 T3 的代谢，这可能是由于 3 型脱碘增加所致。
