Thyroid-stimulating antibody and TSH-binding inhibitor immunoglobulin in 277 Graves’ patients and in 686 normal subjects

Abstract

TSH receptor antibodies (TRAb) are believed to cause hyperthyroidism of Graves' disease. Thyroid-stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) have been measured as TRAb to diagnose Graves' disease and to follow Graves' patients. We intended to evaluate the clinical value of TRAb (TSAb and TBII) assay in establishing the diagnosis of Graves' disease and in predicting its clinical course. TSAb and TBII were studied in 686 normal subjects and in 277 Graves' patients before antithyroid drug therapy. We followed serial changes of TSAb and TBII in 30 Graves' patients before, during and after antithyroid drug therapy over 3.5-9 yr. We measured TSAb as a stimulator assay and TBII as a receptor assay. Both TSAb and TBII were distributed normally in 686 normal subjects. ROC curves demonstrated that both TSAb and TBII had high sensitivity and specificity for the diagnosis of Graves' disease, and were equally sensitive and specific; 150% was chosen as cut-off value for TSAb and 10% for TBII. Of the 277 untreated Graves' patients, 254 (92%) had positive TSAb and positive TBII. All of the 277 untreated Graves' patients had positive TRAb (TSAb and/or TBII). We followed the serial changes of TSAb and TBII in 30 Graves' patients over 3.5-9 yr. During antithyroid drug therapy, TSAb and TBII activities decreased and disappeared in 27 patients (Group A), but continued to be high in the other 3 (Group B). The former 27 Group A patients achieved remission, but the latter 3 Group B patients continued to have hyperthyroidism. Of the 27 Group A patients, 16 (59%) had parallel decreases of TSAb and TBII activities; in 6, the changes were predominantly observed in either TSAb or TBII, and in 4, complex changes in TSAb and TBII activities were observed. Disappearance of TSAb and appearance of TSBAb was seen in one. The other 3 Group B patients continued to have high TSAb and TBII activities and to have hyperthyroidism. In conclusion, TSAb and TBII are of clinical value in establishing the diagnosis of Graves' disease and in predicting its clinical course. We clearly demonstrated its diagnostic usefulness. Both TSAb and TBII have high sensitivity and specificity. All of the 277 untreated Graves' patients had TRAb (TSAb and/or TBII). Serial changes of TSAb and TBII during therapy differ from one patient to another, and can be classified into several groups. Changes in TSAb and TBII activities reflect the clinical courses of Graves' patients. The simultaneous measurement of both TSAb and TBII is clinically useful, since TSAb and TBII reflect two different aspects of TRAb. TSAb and TBII are different.

Recent outcome of Graves’ disease patients with papillary thyroid cancer

“…The autoimmune process of Graves' disease may affect the clinical evolution of thyroid cancer by altering host immune responses. Immunologic remission can be achieved by surgery (12) and during antithyroid drug therapy (13). In this study, the patients who had an immunologic remission of Graves' disease developed cancer metastasis.…”

Association of an A/C single nucleotide polymorphism in programmed cell death-ligand 1 gene with Graves' disease in Japanese patients.

“…GD was diagnosed on the basis of histories and signs of hyperthyroidism with diffuse goiter and the laboratory findings, including elevated serum thyroxine (T 4 ) and tri-iodothyronine (T 3 ) concentrations, undetectable serum TSH levels, and positive TRAb (18,19). TRAb was measured as TSH-binding inhibitory immunoglobulins (TBII) (20) and thyroid-stimulating antibodies (TSAb) (18). TBII was measured using a commercially available kit (RSR Ltd, Cardiff, UK).…”

“…TBII was measured using a commercially available kit (RSR Ltd, Cardiff, UK). A receiver operating characteristic curve analysis (21) was conducted to evaluate the TBII and TSAb values for the GD diagnosis (20). The cutoff value for TBII was 10% (sensitivity 95.67% with 95% confidence limits (93.27-98.07%) and specificity 98.69% with 95% confidence limits (97.84-99.54%)) (20).…”

“…A receiver operating characteristic curve analysis (21) was conducted to evaluate the TBII and TSAb values for the GD diagnosis (20). The cutoff value for TBII was 10% (sensitivity 95.67% with 95% confidence limits (93.27-98.07%) and specificity 98.69% with 95% confidence limits (97.84-99.54%)) (20). TSAb was measured in the same manner as reported previously (18), using a commercially available kit (Yamasa, Chiba, Japan).…”

Thyroid-Stimulating Antibody in a Patient with Euthyroid Graves' Disease.

“…However, the changes in TRAb and TSAb activities do not always parallel each other [18], suggesting that there are heterogeneous antibody activities in sera of patients. There are some reports regarding euthyroid Graves' disease in which TSAb is detectable as frequently as in untreated Graves' disease though the positive rate of TRAb is lower [2,[4][5][6].…”