High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease

Abstract

Context: Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance.

Objective: To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO).

Design: Controlled, follow-up study.

Setting: Academic tertiary referral center for GD + GO.

Subjects: Sixty patients with GD, GD + GO, and controls.

Intervention: Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab.

Main outcome measure: Differentiation among GD phenotypes.

Results: All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P < 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P < 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO.

Conclusions: TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.