Thyroid-stimulating antibodies in patients with long-term remission of Graves' hyperthyroidism

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Abstract
The persistence of TSH receptor antibodies in Graves' disease despite the remission of hyperthyroidism has been described. Our study was designed to evaluate whether this extends to functionally active stimulators of the thyroid, since the occurrence of thyroid-stimulating antibodies (TSAb) in a euthyroid patient could well have important implications on our understanding of the pathogenetic role of such autoantibodies. Forty-four patients with a previous history of Graves' hyperthyroidism were reexamined after having been in long-lasting remission for 3 to 35 years (mean 8 years). Of the patients 16 had been treated by radioiodine, 17 by surgery, and 11 exclusively by antithyroid drugs. The determination of TSAb was based on T3 release from thyroid tissue in vitro to document the final response to these immunoglobulins. TSH-binding inhibiting immunoglobulins (TBII) were evaluated by a radioreceptor assay. TSAb were highly elevated in three of the 44 patients. These three patients showed a normal TSH response to i.v. TRH, suffered from endocrine ophthalmopathy, and had been treated by radioiodine for hyperthyroidism. TBII were found positive in seven patients including the three patients mentioned. The majority of patients positive for TSAb or TBII had been treated by radioiodine and none exclusively by antithyroid drugs. In conclusion, not only TBII but also T3 release-stimulating antibodies may occur in a minority of patients with long-term remission of Graves' hyperthyroidism. However, an absence of hyperthyroidism in these patients despite the presence of such thyroid stimulators seems to be only possible in association with a lack of functional responsiveness of the target organ due to previous administration of destructive therapies. Moreover, a major role of TBII in the absence of TSAb representing stimulatory inactive autoantibodies to the maintenance of remission was not apparent.