Department of Endocrinology and Nephrology, School of Medicine, University of Tokyo, Tokyo, Japan.
Thyroid. 2013 Feb;23(2):151-9. doi: 10.1089/thy.2012.0456.
Thyroid dysfunction is a well-known adverse effect of sunitinib, a drug that targets multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR). As several kinds of tyrosine kinase inhibitors (TKIs) are now available, this has been postulated to be a side effect of the TKIs that target the VEGFR (VEGF-TKIs). However, sunitinib, one of the first-generation TKIs, likely causes thyroid dysfunction more frequently than other TKI classes, leading not only to hypothyroidism, but also to thyrotoxicosis.
Based on the reports published to date, including our own studies, we have hypothesized that sunitinib may exert these effects, because it targets a broad spectrum of tyrosine kinases. This not only includes VEGFR2, but also VEGFR1 and the platelet-derived growth factor receptor (PDGFR). This, in turn, may suggest that not only VEGFR2 but also the PDGFR and/or the VEGFR1 play an important role during angiogenesis in the thyroid.
Our current hypothesis may explain the mechanisms that underlie TKI-induced thyroid disorders. By learning how various kinds of TKIs affect thyroid function, we may elucidate how the angiogenesis in thyroid is regulated both physiologically and pathologically.
甲状腺功能障碍是舒尼替尼的一种众所周知的不良反应，舒尼替尼是一种靶向多种受体酪氨酸激酶的药物，包括血管内皮生长因子受体（VEGFR）。由于现在有几种酪氨酸激酶抑制剂（TKI）可用，因此人们认为这是靶向 VEGFR（VEGF-TKI）的 TKI 的副作用。然而，舒尼替尼是第一代 TKI 之一，它比其他 TKI 类药物更可能导致甲状腺功能障碍，不仅导致甲状腺功能减退症，还导致甲状腺毒症。
根据迄今为止发表的报告，包括我们自己的研究，我们假设舒尼替尼可能会产生这些影响，因为它靶向广泛的酪氨酸激酶。这不仅包括 VEGFR2，还包括 VEGFR1 和血小板衍生生长因子受体（PDGFR）。反过来，这可能表明在甲状腺中的血管生成过程中，不仅 VEGFR2，而且 PDGFR 和/或 VEGFR1 也起着重要作用。
我们目前的假设可以解释 TKI 引起的甲状腺疾病的机制。通过了解各种 TKI 如何影响甲状腺功能，我们可能阐明甲状腺中血管生成是如何在生理和病理条件下受到调节的。
