Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter

Distinguishing Graves' disease (GD) from a toxic multinodular goiter (TMG) subgroup with a diffuse but uneven Tc-distribution depends on the diagnosti c power of the TSH-receptor antibody (TRAb) determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay, which uses the hTSH-receptor as an antigen (DYNOTEST TRAK human, Brahms, Germany), sh owed a higher sensitivity for the detection of TRAbs in patients with GD th an assays using solubilized porcine epithelial cell membranes. The aim of t his study was to investigate whether the new Dynotest TRAK human assay has an increased sensitivity to distinguish GD from non-autoimmune hyperthyroid ism. Therefore, we examined 21 consecutive patients with the initial diagno sis of TMG for thyroid-stimulating antibodies (TSAbs, JP26 cell assay) and TBII with the new highly sensitive Dynotest TRAK human (Brahms, Germany). T he initial diagnosis of TMG was based on suppressed TSH and a patchy Tc-upt ake of more than 1% and less than 7% or TSH of more than 0.3 mIE/l with a p atchy Tc-uptake of more than 1.5% and less than 7% and negative TBII values in a displacement assay using solubilized porcine epithelial cell membrane s (TRAK, Brahms, Germany). 11 sera from these 21 patients showed TSAb activ ity. Furthermore, 10 of these 11 TSAb-positive sera were also positive in t he Dynotest TRAK human assay, whereas one serum sample was borderline posit ive. TSAb activity and inhibition of I-125-bTSH binding in the Dynotest TRA K human assay correlated well (r=0.7). Therefore, 11 of the 21 investigated patients initially classified as TMG actually had GD, which was undetectab le using the porcine TBII assay. In conclusion, TSAbs or TRAbs detected wit h the Dynotest TRAK human have the highest diagnostic power to differentiat e GD from TMG. Because of the less cumbersome assay technique, the Dynotest TRAK human measurements should be obtained for all patients with non-typic al TMG to differentiate GD from non-autoimmune hyperthyroidism in order to select the appropriate therapy for these patients.