Clinical Course of Euthyroid Subjects With Positive TSH Receptor Antibody: How Often Does Graves' Disease Develop?

Background: Thyroid stimulating hormone receptor antibody (TRAb) is detected in the serum of patients with Graves' disease (GD). This study aims to investigate the prevalence of euthyroid individuals showing positive results for TRAb and to clarify the clinical course of thyroid function and TRAb levels in these subjects. Objective: Subjects were female patients who newly visited our hospital for a screening test prior to fertility treatment and showed normal thyroid function and volume without nodules between 2014 and 2017. After excluding subjects with a history of thyroid disease, 5,622 subjects were analyzed. Results: Forty-seven of the 5,622 subjects showed positive results for TRAb (reference range, <2.0 IU/L) at the initial visit. Median initial TRAb was 2.9 IU/L (range, 2.0-14.7 IU/L) and median follow-up was 18.3 months (range, 0-66.5 months). Six of the 47 subjects (12.8%) developed GD and median duration until development was 6.6 months (range, 1.2-13.2 months). Median TRAb values initially and at diagnosis of GD for those 6 patients were 3.7 IU/L (range, 2.7-5.1 IU/L) and 7.2 IU/L (range 3.6-21.4 IU/L), respectively. TRAb results turned negative for 20 of the 47 subjects but remained positive despite normal thyroid function in 13 of the 47 subjects. Conclusion: GD developed over time in 12.8% of euthyroid young female patients showing positive TRAb within a median of 6.6 months. A positive result for TRAb itself did not mean development of GD, so other factors must be essential for the pathogenesis of GD.