THE ROLE OF THYROID-STIMULATING ANTIBODIES OF GRAVES-DISEASE IN DIFFERENTIATED THYROID-CANCER
THE ROLE OF THYROID-STIMULATING ANTIBODIES OF GRAVES-DISEASE IN DIFFERENTIATED THYROID-CANCER
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DOI：
10.1056/nejm198803243181206
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发表时间：
1988-03-24
影响因子：
158.5
通讯作者：
INGBAR, SH
中科院分区：
文献类型：
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作者：
FILETTI, S;BELFIORE, A;INGBAR, SH
大量证据表明促甲状腺激素刺激分化型甲状腺癌的生长和功能。这些反应明显反映了甲状腺癌细胞中存在功能性促甲状腺激素受体，其在结合促甲状腺激素时介导细胞内环AMP浓度的增加，环AMP是促甲状腺激素大多数作用的第二信使。Graves病的特征性循环促甲状腺免疫球蛋白是针对促甲状腺激素受体的抗体;与促甲状腺激素一样，它们激活甲状腺腺苷酸环化酶，并导致本质正常的甲状腺发展为这种疾病的特征性功能亢进和增生。因此，有趣的是，根据临床和实验室结果，Graves病和甲状腺癌以未切除的频率一起发生。这种关联提出了甲状腺刺激抗体可能在甲状腺肿瘤的发病机制和进展中发挥作用的可能性。我们描述了三个并发Graves病和转移性甲状腺癌的患者，他们的临床病程支持这一建议。此外，从这些患者血清中分离IgG的体外研究直接表明，甲状腺癌细胞对甲状腺刺激抗体的反应，就像它们对促甲状腺激素的反应一样。这些发现的一部分已经以摘要的形式提出。
Extensive evidence indicates that thyrotropin stimulates the growth and function of differentiated thyroid carcinomas. These responses evidently reflect the presence in thyroid cancer cells of functioning thyrotropin receptors, which, on binding thyrotropin, mediate an increase in the cellular concentration of cyclic AMP, the second messenger for most actions of thyrotropin. The circulating thyroid-stimulating immunoglobulins characteristic of Graves' disease are antibodies against the thyrotropin receptor; like thyrotropin, they activate thyroid adenylate cyclase and cause the development in the intrinsically normal thyroid of the hyperfunction and hyperplasia characteristic of this disease. Therefore, it is of interest that according to clinical and laboratory findings, Graves' disease and thyroid cancer occur together with unexplected frequency. This association raises the possibility that thyroid-stimulating antibodies may play a part in the pathogenesis and progression of thyroid neoplasms. We describe three patients here with concurrent Graves' disease and metastatic thyroid carcinoma whose clinical courses support this suggestion. Moreover, in vitro studies with IgG isolated from the serum of these patients have demonstrated directly that thyroid carcinoma cells respond to thyroid-stimulating antibodies, as they do to thyrotropin. A portion of these findings has been presented in abstract form.