THE ROLE OF THYROID-STIMULATING ANTIBODIES OF GRAVES-DISEASE IN DIFFERENTIATED THYROID-CANCER

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.