Thyrotropin receptor antibodies in hypothyroid Graves' disease

To clarify the relation of TSH receptor antibody (TRAb) to Graves' ophthalmopathy and thyroid function, the activities of TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies, and thyroid stimulation-blocking antibodies were measured in five patients with hypothyroid Graves' disease. The diagnosis was based on the presence of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of treatment for hyperthyroid Graves' disease. TSH binding inhibitor immunoglobulins and thyroid-stimulating antibodies were detected in all five patients. Thyroid stimulation-blocking antibodies results indicated that a blocking type of TRAb was not a cause of hypothyroidism. Destructive changes in the thyroid were probably responsible for hypothyroidism, since 1) high antibody titers against thyroglobulin and thyroid microsomal antigen, 2) diffuse hypoechogenicity of the thyroid on ultrasonography, 3) absent or impaired responses of serum T3 after TRH or TSH stimulation, and 4) histological findings similar to those in Hashimoto's thyroiditis were observed. In all patients except one, thyroid function was changeable, with euthyroid and even subclinical hyperthyroid episodes occurring during the course of the illness. It is conceivable that such unstable thyroid function may be attributable to subtle changes in the balance between the effects of destructive changes in the thyroid and the stimulatory effects of TRAb. In conclusion, all patients had TRAb, suggesting a possible relationship between such antibodies and Graves' ophthalmopathy. Patients develop euthyroidism or subclinical hyperthyroidism during the course of the illness with high frequency.