Serum Thyroid-Stimulating Antibody,Thyroglobulin Levels,and Thyroid Suppressibility Measurement as Predictors of the Outcome of Combined Methimazole and Triiodothyronine Therapy in Graves' Disease

Abstract

The value of the criteria used to anticipate the outcome of treatment of Graves' hyperthyroid patients with methimazole (MMI) remains controversial. We have reported that high MMI doses combined with T₃ administration was correlated with higher remission rates. In this study, we used the lowest MMI dose able to control the hyperthyroidism, keeping the free T₄ index (FT₄I) values below the normal range throughout treatment, and compared the results with patients treated with a high MMI regimen. Both groups received T₃. We also evaluated the usefulness of goiter size, serum thyroid-stimulating antibody (TSAb: adenylate cyclase stimulation in human thyroid membrane), thyroglobulin (Tg) levels, and the T₃ suppressibility of 24 h RAIU as prognostic markers for the outcome of Graves' disease therapy.

Twenty-four Graves' hyperthyroid patients were treated with high MMI dose (mean ± SD 60 ± 19, range 40-120 mg daily), and 25 patients received low MMI dose (17 ± 4.3, 5-20 mg daily). T₃, 75 μg daily, was given to both groups of patients for 15 ± 4 (13-22) months of treatment. After cessation of drug therapy, 31 patients (63%) remained euthyroid for 18 ± 3 (13-49) months of follow-up, 15 (62.5%) and 16 (64%) patients in the high and low dose groups, respectively. Differences between remission patients and relapse patients at the end of treatment were in the goiter size (41 ± 11 vs 57 ± 22g, p < 0.01), in TSAb activity (83 ± 41 vs 223 ± 150%, p < 0.001), in positive TSAb patients (4/23 vs 12/18, p < 0.01), in T₃ 24 h RAIU (10.9 ± 11 vs 21 ± 17%, p < 0.05), and in T₃ suppressible patients (22/31 vs 6/18, p < 0.02). Serum Tg concentration did not differ between remission (132 ± 242 ng/mL) and relapse (214 ± 235 ng/mL) patients. The combination of serum Tg with TSAb as well as the combination of serum TSAb with T₃ suppressibility improved the predictive value. However, analysis of the specificity and sensitivity showed no significance (<80%) for any predictive markers alone or combined.

T₃ suppressed 24 h RAIU correlated with serum TSAb activity (r = 0.515, p < 0.001) and FT₄I values (r = 0.475, p < 0.02). Serum Tg levels correlated with goiter size (r = 0.38, p < 0.01) but not with T₃ 24 h RAIU, TSAb, or FT₄I values. In conclusion, the secretion of Tg in Graves' disease was related to goiter size. None of the parameters studied was useful for prediction of the outcome of therapy. No difference between the high and the low MMI dose regimens was observed when the MMI was combined with T₃ during the entire treatment period. The remission of Graves' disease might be associated with the maintenance of euthyroidism throughout treatment.