Thyroid-Stimulating Receptor Antibody in Graves Disease The level of TSHRAb of the TBII class grossly parallels the degree of hyperthyroidism as assessed by the serum levels of thyroid hormones and total thyroid volume. Studies suggest that the combination of a small goiter volume (<40 mL) and a low TBII level (<30 U/L) results in a 45% chance of remission during the 5 years after completion of a 12-to 24-month course of antithyroid drug therapy (397). In contrast, the overall rate of relapse exceeded 70% in patients with a large goiter volume (>70 mL) and a higher TBII level (>30 U/L). The subgroup of patients with larger goiters and higher TBII levels had less than a 10% chance to remain in remission in the 5 years after treatment. Although it is not necessary for the diagnosis of Graves disease, except in some cases of multinodular goiter, a TSHRAb measurement may be a useful marker of disease severity. Used in combination with other clinical factors, it may contribute to initial decisions regarding treatment. See Table 31.12 for a review of the nomenclature and assay methods for TSHRAb.
Measurements of TSHRAb (TBII category) during treatment with antithyroid drugs are predictive of subsequent outcome. In one series, 73% of TBII-negative patients had remission compared with only 28% of TBII-positive patients who achieved remission after 12 months of antithyroid drug therapy (398). The duration of a course of antithyroid drug therapy may potentially be modified according to the TSHRAb status. In patients whose TSHRAb status became negative and antithyroid drug therapy was discontinued, the relapse rate was 41% compared with a rate of 92% for those patients who remained TSHRAb positive (399). Regardless of the rapidity of the disappearance of TSHRAb, it does seem that antithyroid drug therapy should be maintained for 9 to 12 months to minimize the risk of relapse. TSHRAb status appears to determine, in an inverse relationship, the reduction in thyroid volume after radioactive iodine therapy.
Third-generation TSHRAb assays have been developed, and their utility in evaluation and treatment monitoring is being evaluated. Many patients with Graves disease have or will develop antineutrophil cytoplasmic antibodies (ANCA) after treatment, but the significance of this finding is still under study. Smoking appears to be an independent risk factor for relapse after medical therapy and should be considered when planning treatment.
Antithyroid Drugs Antithyroid drugs of the thioamide class include propylthiouracil (PTU) and methimazole. Low doses of either agent block the secondary coupling reactions that form T3 and T4 from MIT and DIT. At higher doses, they also block iodination of tyrosyl residues in thyroglobulin. Propylthiouracil additionally blocks the peripheral conversion of T4 to T3. Approximately one-third of patients treated by this approach alone go into remission and become euthyroid (397).