Prognostic Value of Suppressed Thyrotropin Level and Positive Thyrotropin-Receptor Antibody Activity in Graves’ Disease with Long-Lasting Clinical Remission

Abstract

To determine the prognostic value of suppressed thyrotropin (TSH) level and positive TSH-receptor antibodies (TSH-R Ab) in patients with Graves' disease who have long-lasting clinical remission. We retrospectively studied patients with Graves' disease who underwent follow-up for a mean of 55 months after the withdrawal of antithyroid drug treatment. Study patients were 84 consecutive subjects in clinical remission, with normal serum free thyroxine (FT(4)) and free triiodothyronine (FT(3)) levels, regardless of serum TSH levels, a mean of 35 months (range, 6 to 135) after discontinuation of carbimazole therapy. Eighty-seven euthyroid subjects were used as control study participants. All subjects had serum determinations of FT(4) and FT(3) (radioimmunoassay), TSH (highly sensitive immunoradiometric method), TSH-R Ab (radioreceptor assay), and microsomal antibodies (M Ab, passive hemagglutination method). In the study patients, serum TSH was suppressed (</=0.10 mU/L) in 13 cases (15%), TSH-R Ab were positive (>/=15%) in 11 cases (13%), and M Ab were positive (>/=1:100) in 54 cases (64%). Simultaneous suppressed TSH and positive TSH-R Ab levels were present in six patients. During the follow-up, 11 patients had a relapse, demonstrated by above-normal values for serum FT(4) and FT(3) in association with clinical symptoms of hyperthyroidism. Five of them had a previously suppressed TSH level, three had a positive TSH-R Ab level, and six had a positive M Ab titer. Relapse was significantly more likely in patients with a previously suppressed TSH level (P<0.02) but not in patients with a previously positive TSH-R Ab level or positive M Ab titer. Patients with Graves' disease and long-lasting clinical remission after discontinuation of carbimazole therapy may have a suppressed TSH level, a positive TSH-R Ab level, or a positive M Ab titer (or some combination of these findings). Although positive TSH-R Ab and M Ab have no significant prognostic value, a suppressed TSH level is indicative of subclinical hyperthyroidism and higher risk of relapse.