Abstract
Objective: Graves\ disease (GD) hyperthyroidism provoked by stimulating TSHR autoantibodies (sTRAb) is accompanied in 50 % by thyroid associated ophtalmopathy (TAO). It has been demonstrated that TSHR is expressed in the orbit (fibroblasts, pre-adipocytes). Also lymphocyte infiltrations are found in orbital tissue in TAO. The aim of this report is to elucidate the effect of retrobulbar radiation therapy on the suggested orbital autoimmune process in the orbit of thyroidectomised patients with GD and TAO.
Methods: Stimulating TSHR autoantibodies were measured by novel bridge assay on microplates using recombinant chimeric hTSHR-LH/CG receptors (chim-hTSHR) where the epitope for blocking autoantibodies (Ab) is replaced. By capture chim-hTSHR sTRAb are detected and finally measured by signal chim-hTSHR. Six patients with active GD and TAO were subjected to retrobulbar radiation therapy (12-16 Gy) after subtotal thyroidectomy. Resected tissues demonstrated typical GD pathology. A further patient was completely thyroidectomised because of papillary thyroid carcinoma before radiation. All patients had to be under thyroxin substitution (150 to 175 ?g/d) after surgery.
Results: Retrobulbar radiation therapy led to improvement of the clinical picture of TAO in six cases. sTRAb values, which after surgery decreased and remained stable at 16,0; 14,1; 3,3; 4,8; 5,3 and 32.8 IU/L, further decreased in six patients markedly (by 45 %; 72 %; 50 %; 54 %; 68 % and 52%). In the patient with complete thyroidectomy excessively active TAO was persistent and sTRAb values remained constant between 16,8 and 18,2 IU/L over the observation period of several months.
Conclusions: These data suggest that TSHR expressed in the orbit of patients with TAO causes autoimmune process with extrathyroidal production of sTRAb in the orbital tissue. In parallel with clinical improvement of TAO, retrobulbar radiation therapy leads to decrease in the autoimmune process whereas in resistent active TAO sTRAb production and autoimmune process remain present.