Nature of thyrotropin displacement activity in subacute thyroiditis

Using a radioreceptor assay and serum immunoglobulin (Ig) prepared by ammonium sulfate precipitation, significant TSH displacement activity (TDA) was demonstrated in 5 of 15 patients with subacute thyroiditis tested during the acute phase. Using a cAMP generation assay, adenyl cyclase stimulation by Ig from patients with subacute thyroiditis was not demonstrated. The nature of the TDA demonstrated in subacute thyroiditis was investigated to determine whether the factor measured was TSH receptor antibody, as is found in Graves' hyperthyroidism, or thyroglobulin, which is know to give false positive responses in the radioreceptor assay. When Ig was prepared by DEAE+-Sephadex chromatography, mean TSH displacement indices were similar to those given by ammonium sulfate-prepared Ig for both Graves' disease and subacute thyroiditis. On the other hand, when Ig was prepared by DEAE+-cellulose chromatography, which isolates highly purified IgG, mean indices were significantly less than for ammonium sulfate-prepared Ig for both Graves' hyperthyroidism and subacute thyroiditis. Thyroglobulin was not detected in Ig prepared by any of the 3 methods. Although high concentrations of crude thyroid-soluble fraction and purified thyroglobulin gave strongly positive responses in the radioreceptor assay, concentrations of thyroglobulin over the range found in the sera of patients with subacute thyroiditis could not be shown to give positive responses. Moreover, TSH displacement indices did not correlate with serum thyroglobulin levels. As determined by species cross-reactivity and dose-responses studies, the TDAs demonstrated in subacute thyroiditis and Graves' hyperthyroidism were similar. It was concluded that the TDA demonstrated in subacute thyroiditis represents antibody which binds to, but does not stimulate, the TSH receptor.