Graves' ophthalmopathy in the absence of elevated free thyroxine and triiodothyronine levels: Prevalence, natural history, and thyrotropin receptor antibody levels

The aims of this study were to (a) determine the prevalence of patients wit hout elevated thyroid hormone levels in Graves' ophthalmopathy (GO) using c urrent generation free thyroid hormone assays, (b) measure the prevalence o f thyrotropin receptor antibodies (TRAb) in these cases, and (c) identify p ossible predictors of hyperthyroidism. Over a 30-month period, 1020 cases o f thyroid eye disease were evaluated, of which only 19 (1.9%) met the diagn ostic criteria. Ten (1%) had subclinical thyrotoxicosis, 7 (0.7%) were euth yroid, and 2 (0.2%) were hypothyroid as determined by a third-generation th yrotropin (TSH) assay. TRAb levels were measured in 16 of these 19 patients . The prevalence of TRAb varied according to the assay used. Polyethylene g lycol-extracted thyroid-stimulating immunoglobulin (PEG-TSI), unfractionate d thyroid-stimulating immunoglobulin (uTSI), first-generation porcine TSH-b inding inhibitory immunoglobulin (pTBII), and second-generation human TSH-b inding inhibitory immunoglobulin (hTBII) assays were positive in 93.8%, 50% , 18.8%, and 81.3% of patients, respectively. TRAb was detected by at least one method in all patients. Patients were followed up for 15 to 45 months. Hyperthyroidism developed in 4 patients (25%). Suppressed TSH levels and e levated TBII were predictors of hyperthyroidism. When sensitive assays are used, the prevalence of GO patients without elevated thyroid hormone levels is extremely low. The sensitivities of assays for TRAb detection differ su bstantially in these cases. PEG extraction improves the detection rate of T SI (p = 0.02), and hTBII assays improve the detection of TBII in these pati ents (p = 0.002). The high prevalence of TRAb in such cases supports a role for these antibodies in the pathogenesis of thyroid-associated eye disease .