The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves' disease

Abstract

Background: The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines.

Methods: A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves' disease.

Results: A total of 77 patients with Graves' disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves' disease (p < 0.001). Under anti-thyroid drugs treatment, thyroid-stimulating immunoglobulin value decreased gradually. A total of 21 patients had positive thyroid-stimulating immunoglobulin at the end of treatment. According to clinical fate of patients with Graves' disease after withdrawal of anti-thyroid drugs, thyroid-stimulating immunoglobulin value and positivity in patients with relapse were significantly higher than that reported in patients with remission (p = 0.001, p < 0.001). After adjustment for age, gender, initial thyroid receptor antibody, initial thyroid-stimulating immunoglobulin, and thyroid receptor antibody at the end of treatment, the odds ratio of positive thyroid-stimulating immunoglobulin for the risk of relapse was 33.271 (95% confidence interval: 4.741-233.458, p < 0.001) and odds ratio of quantitative thyroid-stimulating immunoglobulin was 1.009 (95% confidence interval: 1.002-1.015, p < 0.001).

Conclusion: Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves' disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

Keywords: Graves’ disease; autoimmune thyroiditis; thyroid-stimulating immunoglobulin; thyrotoxicosis; thyrotropin receptor antibody.

Figure 1.

Comparison analysis of TSH-binding inhibition assay and thyroid-stimulating immunoglobulin (TSI) in healthy control and different etiologies of thyrotoxicosis. According to thyroid function and treatment, patients were divided into untreated GD group (new-onset), GD undertreatment group, and GD at the end of treatment. (a) TRAb titers using TSH-binding inhibition assay and (b) thyroid-stimulating immunoglobulin (TSI) values in healthy control and different etiology of thyrotoxicosis. p values were calculated by Mann–Whitney U test.

Figure 2.

Higher relapse rate in positive thyroid-stimulating immunoglobulin (TSI) group at the end of anti-thyroid treatment in patients with Graves’ disease. (a) Relapse rate in positive and negative thyroid-stimulating immunoglobulin (TSI) group, respectively. p value was calculated by a chi-square test; (b) the change of TSI from the end of treatment to 1 year after stopping medication in Graves’ disease patients with relapse (n = 4) or with remission (n = 11) at the end of treatment.