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PURPOSE: The purpose of this study was to elucidate the mechanism of regulation of serum thyroglobulin concentration in patients with Graves' disease and to establish the clinical usefulness of this measurement. PATIENTS AND METHODS: Serum thyroglobulin concentration was analyzed in relation to serum thyrotropin receptor antibody (TRab) titer and thyrotropin concentration in 166 patients with Graves' disease without thyroglobulin antibody. RESULTS: A total of 113 patients were treated and had been kept euthyroid for at least 10 months with methimazole and underwent a triiodothyronine (T[.sub.3]) suppression test. At the time of the T[.sub.3] suppression test, the serum thyroglobulin concentration ng/mL) was 33 [+ or -] 31 in 80 of them with T[.sub.3]-suppressible (radioiodine uptake less than 12%) thyroids, negative TRab titers (less than 15% displacement), and normal serum thyrotropin concentrations (0.1 to 3.0 mU/L). Patients with T[.sub.3]-nonsuppressible thyroids were divided into three subgroups according to serum TRab titers and thyrotropin concentrations: those with a negative TRab titer and a normal serum thyrotropin concentration (n = 9), those with a positive TPab titer and a normal thyrotropin concentration (n = 18), and those with a positive TRab titer and undetectable thyrotropin (n = 6). Serum thyroglobulin concentrations (ng/mL) were 116 [+ or -] 40 in the first group, 249 [+ or -] 194 in the second group, and 399 [+ or -] 205 in the third group. In the other 39 methimazole-treated patients, 72 determinations of serum thyroglobulin concentration were performed either before or during treatment without the T[.sub.3] suppression test, and it correlated well with the TRab titer but not with the serum thyrotropin concentration. In 14 patients who became hypothyroid due to excess methimazole, the serum thyroglobulin concentration increased concurrently with elevation of the serum thyrotropin concentration and normalized during thyroxine supplementation. In treated patients with T[.sub.3]-suppressible thyroids, the serum thyroglobulin concentration was similar among those with positive (n = 54) and negative (n = 26) microsomal antibody, indicating that the presence of Hashimoto's thyroiditis does not profoundly affect the serum thyroglobulin level. Among 80 patients with T[.sub.3]-suppressible thyroids who were followed without methimazole for a mean period of 31.1 months, eight (10%) experienced a clinically overt recurrence of hyperthyroidism. Serum thyroglobulin concentration and TRab titer %) in these eight patients were 188.1 [+ or -] 101.7 and 27.8 [+ or -] 12.6, respectively. Thyroglobulin and TRab did not increase in the patients who remained euthyroid (n = 71) or who experienced subclinical recurrence (n = 1). CONCLUSIONS: Abnormal thyroid stimulator(s) and thyrotropin synergistically (if both are present in the serum) or independently (if either one is present) stimulate thyroglobulin secretion in patients with Graves' disease. Therefore, serum thyroglobulin concentration can be a useful means of assessing the degree of thyroidal stimulation and, if serum thyrotropin is normal or suppressed, correlates well with thyroidal stimulation even in patients with a negative TRab titer., Graves' disease is characterized by an enlarged thyroid gland and abnormal protrusion of the eyeballs. The regulation of blood levels of thyroglobulin, an iodine-containing protein released by the thyroid gland, was assessed in patients with Graves' disease. Thyroglobulin levels were assessed in relation to levels of the pituitary hormone thyrotropin, which stimulates the thyroid gland, and the presence of antibodies, or immune proteins, that specifically bind to receptors for thyrotropin (TRab). One hundred and thirteen patients were treated with the antithyroid drug methimazole and their thyroid activities were maintained at normal levels for at least 10 months. Blood levels of thyroglobulin averaged 116 nanograms per milliliter (ng/mL) in nine patients with normal thyrotropin levels and no TRab, 249 ng/mL in 18 patients with TRab but normal thyrotropin levels, and 399 ng/mL in six patients with TRab and undetectable thyrotropin levels. In another 39 patients treated with methimazole, thyroglobulin levels were correlated with the levels of TRab but not thyrotropin. Among 14 patients with hypothyroidism or low thyroid activity due to excessive treatment with methimazole, thyroglobulin levels increased with rising thyrotropin levels, but became normal with supplements of the thyroid hormone thyroxine. Among eight patients with recurrent hyperthyroidism or increased activity of the thyroid gland, thyroglobulin measured 188 ng/mL and TRab at almost 28 percent. Patients with normal thyroid activity or mild recurrence of hyperthyroidism maintained low levels of thyroglobulin and TRab. These findings suggest that thyrotropin and abnormal factors that stimulate the thyroid gland control the release of thyroglobulin in patients with Graves' disease. Measurement of thyroglobulin levels provides a means of assessing the activity of the thyroid gland. (Consumer Summary produced by Reliance Medical Information, Inc.)

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