Association of thyrotrophin receptor antibodies with the clinical featuresof Graves' ophthalmopathy

OBJECTIVE Graves' ophthalmopathy (GO) and Graves' hyperthyroidism are close ly associated diseases and thought to be caused by the same autoimmune proc ess. An obvious explanation for this would be the presence of autoantibodie s reacting with an autoantigen present in the orbit and the thyroid gland. The TSH-Receptor (TSH-R) antibodies are a likely candidate, because they ca use Graves' hyperthyroidism and the TSH-R appears to be present also in orb ital tissues. If TSH-R antibodies are responsible for the ophthalmopathy on e would expect their titres to correlate with clinical characteristics of t he eye disease. The aim of the present study is to see whether TSH-R antibo dies are related to the activity and severity of the thyroid-associated oph thalmopathy. DESIGN AND PATIENTS TSH-R antibody levels were measured as TBII (TRAK assay ), and TSI (cAMP response of a TSH-R transfected cell line) in serum of 63 patients with untreated moderately severe GO, accompanying Graves' thyroid disease; all patients had been euthyroid for > 2 months. RESULTS TBII and TSI titres were strongly related to each other. TBII or TS I titres did not correlate with thyroidal or orbital disease duration, nor with TPO antibody levels. In contrast, we found a striking and highly signi ficant correlation between the Clinical Activity Score (CAS) of the eye dis ease, and both TBII (r = 0.54; P < 0.0001) and TSI (r = 0.50; P < 0.0001). In addition, a weaker but significant relation was found between proptosis (in mm) and TBII (r = 0.36; P = 0.004) and TSI (r = 0.49; P = 0.0001). No c orrelation was found with eye muscle motility. CONCLUSION TSH-R antibody levels correlate directly with clinical features of Graves' ophthalmopathy. The results support the hypothesis of a pathogen etic role of TSH-R antibodies and the TSH-R in the orbit of Graves' ophthal mopathy patients.