Sensitive TSH and TSH-receptor antibody determinations as predictors of relapse in Graves' disease

Abstract

After primary successful antithyroid drug treatment (ATDT), Graves' disease (GD) has a relapse rate of 30 to 50%. Despite higher sensitivity and specificity of the new second generation human TSH receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of GD. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism. Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third generation TSH assay and a second generation recombinant TSH receptor assay. Relapse of GD was evaluated for a total follow-up of two years. Within two years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first four weeks after withdrawal of ATDT and were thus considered to have persistent GD. Ten of fifteen other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism developed relapse within two years. Twenty-five of 65 patients with normal TSH had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of GD. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L±0.17) than TRAb values in the remission group (4.5 IU/L±0.6), p<0.001. Using a cut-off value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity 14%), but with a cut-off level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity 92%). In conclusion, low TSH values four weeks after ATDT withdrawal predict relapse of GD, both early (persistence) and, to a lesser extend, within two years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.