Sensitive thyroid-stimulating antibody assay with high concentrations of polyethylene glycol for the diagnosis of Graves' disease

1. The aim of the present study was to determine the usefulness of a newly developed thyroid-stimulating antibody (TSAb) assay. We developed a highly sensitive TSAb (sTSAb) assay with 22.5% polyethylene glycol-precipitated crude IgG. The thyroid-stimulating hormone (TSH) receptor antibody (TRAb) causes Graves' disease and TRAb has been measured as TSH-binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb). The TSAb stimulates the thyroid glands and causes hyperthyroidism. In addition to investigating the usefulness of the newly developed sTSAb assay, we also investigated the frequencies of positive TRAb in thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. 2. We studied 700 untreated Graves' patients with hyperthyroidism and 923 normal controls. We also studied thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. Conventional TSAb (cTSAb) and sTSAb were measured as TSAb, whereas porcine TBII (pTBII) and human recombinant TBII (hTBII) were measured as TBII 3. Levels of cTSAb and sTSAb were determined in 923 normal controls and 629 untreated Graves' patients and cTSAb and sTSAb were found to be normally distributed in normal controls, but not in untreated Graves' patients. Receiver operating characteristic (ROC) curve analysis demonstrated that cTSAb and sTSAb had high sensitivity and specificity for Graves' disease. Of the patients investigated, 96.5% of untreated Graves' patients were positive for sTSAb and/or pTBII. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb. Paired determinations of cTSAb and sTSAb were performed in 146 untreated Graves' patients. A positive correlation was found between cTSAb and sTSAb. Titres of sTSAb were higher than those of cTSAb and sTSAb had high sensitivity. 4. Of the 35 untreated Graves' hyperthyroid patients who were negative for cTSAb, 18 (51%) were positive for sTSAb. Of the 36 untreated Graves' patients who were negative for hTBII, nine (25%) were positive for sTSAb. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb and some who were negative for hTBII and pTBII were positive for sTSAb. 5. Some thyrotoxic patients with subacute thyroiditis or painless thyroiditis were positive for TRAb. However, the frequency of TRAb-positive patients was low in this group. None of the patients with a solitary toxic nodule was positive for TRAb. 6. In conclusion, sTSAb had higher sensitivity than cTSAb. Graves' patients who were cTSAb negative and hTBII negative could be sTSAb positive. The sTSAb indicates TSAb activity, but pTBII and hTBII do not necessarily do so. We recommended that the sTSAb is used in Graves' patients.