Effect of thyroxine administration on serum thyrotropin receptor antibody and thyroglobulin levels in patients with Graves' hyperthyroidism during antithyroid drug therapy

Abstract

Kuo SW, Huang W-S, Hu C-A, Liao W-K, Fung T-C, Wu S-Y. Effect of thyroxine administration on serum thyrotropin receptor antibody and thyroglobulin levels in patients with Graves' hyperthyroidism during antithyroid drug therapy. Eur J Endocrinol 1994;131:125–30. ISSN 0804–4643 Graves' hyperthyroidism is due primarily to overproduction of antibodies to thyrotropin receptors (TR-ab), which stimulate the thyroid gland and cause hyperthyroidism. Antibody production during antithyroid drug therapy is an important determinant of the course of the disease. We therefore observed the changes of serum TR-ab, thyroglobulin (Tg) and thyroid hormone levels in response to administration of l-thyroxine (T4) in Graves' hyperthyroid patients during antithyroid drug therapy. Serum levels of TR-ab, Tg and other thyroid hormones were measured by radioimmunoassay (RIA) during either methimazole treatment alone or in combination with thyroxine in 60 Graves' hyperthyroid patients. The patients initially were treated with 30 mg of methimozole daily for 3 months, which was then reduced to 15 mg daily for the following 3 months. All patients were euthyroid 6 months after the start of antithyroid therapy and the TR-ab level decreased from 61 ± 11% (±sd) to 28 ± 7% (p < 0.01). Patients then were divided into three groups: group A (N = 25), whose TR-ab level was 10% or more (the cut-off value for positivity), received 0.1 mg of T4 and 10 mg of methimazole daily for 6 months; group B (N = 15), whose TR-ab level also was 10% or more and was age- and thyroid function-matched with group A, received only 10 mg of methimazole daily for 6 months; group C (N = 20), with a TR-ab level of less than 10%, received 10 mg of methimazole alone daily for 6 months. In the T4-treated group (group A), the mean serum T4 level increased from 66 ± 21 to 117 ± 30 nmol/l (p < 0.05) and the TR-ab and Tg concentrations decreased from 38 ± 11 to 10 ± 5% (p < 0.01) and 135 ± 25 to 45 ± 12 μg/l (p < 0.01), respectively, after 6 months of combination therapy. In the non-T4-treated groups (groups B and C), the mean serum T4, TR-ab and Tg levels did not change significantly (p > 0.05). Serum TR-ab levels at the end of the combination therapy (group A) were significantly lower than with methimazole alone (27 ± 11%, p < 0.05). Serum TR-ab levels correlated positively with the serum Tg concentrations and ultrasonogram-measured thyroid volume in untreated (r = 0.281, p < 0.05 and r = 0.485, p < 0.001, respectively) and treated (r = 0.288, p < 0.05 and r = 0.480, p < 0.001, respectively) Graves' hyperthyroid patients after the first 6 months of methimazole therapy. A positive correlation was found between thyroid volume and serum Tg concentration before (r = 0.31, p < 0.01) and after (r = 0.450, p < 0.001) the first 6 months of methimazole therapy. However, the serum levels of thyrotropin were not correlated with those of TR-ab and Tg (p > 0.05) after methimazole therapy. In summary, the present study demonstrated a greater fall in serum TR-ab and Tg levels in patients with Graves' disease treated with combined methimazole and T4 than with methimazole alone. Sing-Yung Wu, Station 151, Department of Nuclear Medicine and Medical Services, VA Medical Center, Long Beach, CA 90822, USA