Bioassay of thyroid-stimulating immunoglobulin in cryopreserved human thyroid cells: optimization and clinical evaluation.

We have explored the method of Rapoport et al. (J Clin Endocrinol Metab 1984;58:332-8) for the bioassay of thyroid-stimulating immunoglobulin (TSI) in cultured human thyroid cells, to optimize the assay and to evaluate its utility in clinical diagnosis and management of patients with autoimmune thyroid disease. Here we describe the procedure ultimately adopted, its major properties, and the results it has yielded in various clinical states. Clinical sensitivity of the assay was established by demonstrating TSI activity in all of 60 cases of active Graves' disease. We observed in these patients a nonlinear correlation between concentrations of TSI and of triiodothyronine, as well as between TSI concentration and the clinical severity of the thyrotoxicosis. Specificity of the assay was demonstrated by finding no TSI bioactivity in 13 patients with toxic adenoma, five with cold nodule, and 18 of 19 with nontoxic goiter. Remission of Graves' disease in 25 patients was invariably accompanied by undetectable concentrations of TSI; evidently this assay may be useful in identifying patients who are likely to go into remission. TSI activity was present in eight of 11 patients with euthyroid ophthalmopathy (unilateral and bilateral) associated with a normal response to the thyrotropin-releasing hormone test and absence of increased titers of antithyroid antibodies, suggesting that this assay may provide a powerful tool in the clinical diagnosis of this disorder.