Background
Serum thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies are etiologically important for Graves’ disease (GD) by promoting both function and growth of thyroid follicular cells, leading to hyperthyroidism and goiter. To date, the preferred method for clinical convenience is the thyrotropin-binding inhibitory immunoglobulin (TBII) assay, although this method cannot differentiate stimulating from blocking antibodies. TBII concentrations help diagnose Graves’ ophthalmopathy and predict the clinical course of the eye disease (1), and in pregnant GD patients, maternal TBII levels in the latter half of pregnancy are associated with fetal and neonatal hyperthyroidism (2). The purpose of this study (3) was to investigate changes in the TBII concentrations of patients undergoing total thyroidectomy (TTx) or radioactive iodine (RAI) therapy for GD refractory to conventional antithyroid drug (ATD) therapy.

Methods
The study (3) was a retrospective review of hospital medical records of 130 patients with previous ATD use who were undergoing TTx or RAI therapy for GD between January 2011 and December 2017 at Samsung Seoul Hospital, Seoul, Korea. All required definitive treatment after sufficient ATD use and had TBII measurements before and at least once within 1 year after treatment. The median number of follow-up TBII measurements was 3 (range, 1–8). Exclusion criteria were side effects of ATDs or other comorbidities in the TTx group, thyroid lobectomy prior to TTx or RAI, TTx after RAI failure, and multiple courses of RAI.

Serum free thyroxine (FT4), total triiodothyronine (TT3), and TSH concentrations were measured using radioimmunoassay methods. Hyperthyroidism was defined as TSH ≤0.05 mU/L. TBII positivity was characterized by titers >1.5 U/L measured by a second-generation TRAK human assay. Survival analysis was performed for the normalization of TBII titers, defined as levels <4.5 IU (3× the upper limit of normal, which is known to be a risk factor for fetal hyperthyroidism).

Results
Patients in the TTx group more often had higher TT3 and positive TBII titers. They were also more likely to have goiter and ophthalmopathy, and they were younger, required higher ATD doses, and had fewer arrhythmias than those in the RAI group. All patients in the TTx group (100%) reached hypothyroidism immediately after the treatment. On the other hand, 35 patients (41.2%) who had undergone RAI therapy had recurrent hyperthyroidism, and 16 (18.8%) did not experience remission during the 2-year study period. TBII levels continued to decrease in the TTx group following treatment, while, conversely, TBII levels increased for 138 days (estimated median value) and decreased slowly thereafter in the RAI group. There were statistically significant differences in TBII levels between the two groups at 6 and 9 months after treatment. In the RAI group, high levels of TBII (>4.5 IU/L) were present in 70 patients (82%) at 6 months, 57 (67%) at 1 year, and 3 (3%) at 2 years. In the RAI group, goiter was associated with a longer time for the TBII levels to decrease (P<0.05) (see table). The duration of prior ATD use was not associated with TBII reduction in either group.

Conclusions
The authors concluded that changes in TBII levels following TTx or RAI therapy were different in these two groups among patients with refractory GD. This difference should be taken into account when TTx or RAI therapy is considered, together with patient age, severity of hyperthyroidism, goiter, ophthalmopathy, and future pregnancy plans for young female patients.