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Journal of Clinical Endocrinology & Metabolism, Vol 64, 718-722, Copyright © 1987 by Endocrine Society


ARTICLES

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment

H Tamai, Y Hirota, K Kasagi, S Matsubayashi, K Kuma, Y Iida, J Konishi, MC Okimura, RM Walter and LF Kumagai

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.


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