Autoimmune-resistance in Graves' disease tissues indication of a structural and functional heterogenicity

Out of 256 patients with Graves' disease and a characteristically low echogenic ultrasound appearance of the thyroid gland, 12 patients (4.7%) showed additionally one single or several intrathyroidal focal alterations with high echogenicity. Their volume was 0.2 to 7.0 cm (X +/- SD: 1.75 +/- 2.24 cm). A common characteristic of the 12 patients was a longstanding history of Graves' disease and antithyroid treatment with thiamazol or carbimazol and a mean age of 55 +/- 9 (SD) years (range 42-75 years). The foci with high echogenicity had a normal or macrofollicular histological structure (mean follicle lumen diameter 119.7 micron, as proven by histology in 4 cases) which was significantly higher than follicle lumina of the surrounding Graves' disease tissue (mean follicular lumen diameter 38.3 micron; P greater than 0.001). The height of follicle epithelium and the nuclei cross-section area of such foci was similar to corresponding normal tissue parameter in 5 out of 7 foci. The 99mTc-uptake of the foci amounted to 40 to 80% in comparison with Graves' disease tissue. 131-iodine autoradiography, thyroglobulin immunochemistry and 125-iodine-TSH binding analysis performed in selected cases confirmed the heterogenicity of these foci. The data provided evidence that the foci were unresponsive to TSH-receptor mediated stimulation through Graves' immunoglobulins. It is concluded that longstanding Graves' disease can be associated with tissue foci which are in a functional sense resistant to immunogenic stimulation by TSH-receptor autoantibodies.