Antibodies that block stimulation by TSH or TSAb of thyroid hormone secretion in primary hypothyroidism

Antibodies that inhibit the stimulation of the thyroid by TSH have been studied in 63 patients with primary hypothyroidism of whom 34 had thyroid atrophy and 29 goitrous Hashimoto's thyroiditis. The method used measured the secretion of tri-iodothyronine (T3) from porcine thyroid slices incubated in vitro. The aims of the study were to assess the frequency and clinical correlates of blocking antibodies in an unselected series of patients, to establish their IgG nature and to examine their action in relation to the TSH receptor. Blocking antibodies were found in 25% of patients and occurred in association with both atrophic (32%) and goitrous (17%) hypothyroidism. These antibodies did not bind TSH (with one exception) nor did they inhibit binding of TSH to its receptor (also with one exception). Blocking-antibody activity was abolished by treatment of the serum with anti-hIgG or with protein A, and the activity was purified from serum by affinity chromatography on protein A sepharose-4B, thus establishing the IgG nature of the antibodies. The stimulation of T3 secretion by thyroid-stimulating antibodies was also blocked and in one case, where IgG did not block stimulation by bTSH, stimulation by hTSH was blocked. Antibodies blocking the action of TSH probably represent an important mechanism in the pathogenesis of primary hypothyroidism in some patients.