Prospective Trial of Functional Thyrotropin Receptor Antibodies in Graves Disease

CONTEXT: Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD). OBJECTIVE: To evaluate the clinical utility and predictive value of TSAb/TBAb. DESIGN: Prospective 2-year trial. SETTING: Academic tertiary referral center. PATIENTS: One hundred consecutive, untreated, hyperthyroid GD patients. METHODS: TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibition). MAIN OUTCOME MEASURES: Response versus nonresponse to a 24-week methimazole (MMI) treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. RESULTS: Forty-four patients responded to MMI, of whom 43% had Graves orbitopathy (GO), while 56 were nonresponders (66% with GO; P < 0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibitory immunoglobulins (TBII) differentiated between thyroidal GD-only versus GD + GO (P < 0.001). Furthermore, at baseline, responders demonstrated marked differences in diluted TSAb titers compared with nonresponders (P < 0.001). During treatment, serum TSAb levels decreased markedly in responders (P < 0.001) but increased in nonresponders (P < 0.01). In contrast, TBII strongly decreased in nonresponders (P = 0.002). All nonresponders and/or those who relapsed during 72-week follow-up period were TSAb-positive at week 24. A shift from TSAb to TBAb was noted in 8 patients during treatment and/or follow-up and led to remission. CONCLUSIONS: Serum TSAb levels mirror severity of GD. Their increase during MMI treatment is a marker for ongoing disease activity. TSAb dilution analysis had additional predictive value.