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Thyrotropin Receptor Autoantibodies Are Associated with Continued Thyrotropin Suppression in Treated Euthyroid Graves’ Disease Patients

Department of Endocrinology and Metabolism, University of Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Leon J. S. Brokken, Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. E-mail: Leon.Brokken{at}utu.fi.

Antithyroid treatment effectively restores euthyroidism in patients with Graves’ hyperthyroidism. After a few months of treatment, patients are clinically euthyroid with normal levels of thyroid hormones, but in many patients TSH levels remain suppressed. We postulated that TSH receptor autoantibodies could directly suppress TSH secretion, independently from thyroid hormone levels, via binding to the pituitary TSH receptor. To test this hypothesis, we prospectively followed 45 patients with Graves’ hyperthyroidism who were treated with antithyroid drugs. Three months after reaching euthyroidism, blood was drawn for the analysis of thyroid hormones, TSH, and TSH binding inhibitory Ig (TBII) levels. After 6.7 ± 1.5 months since start of antithyroid treatment, 20 patients still had detectable TBII levels, and 25 had become TBII negative. The two groups had similar levels of free T₄ and T₃, but TBII-positive patients had lower TSH values than TBII-negative patients: median 0.09 (range < 0.01–4.30) mU/liter vs. 0.84 (0.01–4.20; P = 0.015). In addition, TSH levels correlated only with TBII titers (r = -0.424; P = 0.004), and not with free T₄ or T₃ values.

Our findings suggest that TBII suppress TSH secretion independently of thyroid hormone levels, most likely by binding to the pituitary TSH receptor.

Abbreviations: FT₃I, Free T₃ index; fT₃, free T₃ fT₄, free T₄; TBII, TSH binding inhibitory Ig; TSH-R, TSH receptor; TSI, TSH-R-stimulating Igs.