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Development of Spontaneous Hypothyroidism in Patients with Graves' Disease Treated with Antithyroidal Drugs: Clinical, Immunological, and Histological Findings in 26 Patients

Department of Psychosomatic Medicine, Faculty of Medicine, Kyushu University Fukuoka
Kuma Hospital Kobe
Department of Nuclear Medicine, Kyoto University, School of Medicine Kyoto
First Department of Internal Medicine, Nagasaki University, School of Medicine Nagasaki, Japan
Department of Internal Medicine, School of Medicine, University of California, Davis Sacramento, California 95817

Address all correspondence and requests for reprints to: Dr. Hajime Tamai, Department of Psychosomatic Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan.

Graves' disease may result eventually in hypothyroidism in approximately 5–20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding nhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5–10 yr or more after discontinuation of antithyroid drug therapy.

Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia.

We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

Received November 15, 1988.

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