Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease

Abstract

The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = -0·86, P < 0·05). The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with > 70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.

Keywords: Graves' disease; Hashimoto's thyroiditis; TSH-receptor blocking antibodies; TSH-receptor stimulating antibodies; bioassay.

Figure 1

Distribution of thyroid stimulating hormone receptor‐stimulating antibodies (TSAb) (a) and TSHR‐blocking antibodies (TBAb) (b) in 133 TBAb‐positive serum samples with autoimmune thyroid disease (AITD). (a) The dots demonstrate TSAb measured in the TSAb bioassay (cut‐off at 140 specimen‐to‐reference ratio (SRR %) as a dotted line. Included in the red circle are the 10 TBAb‐ and TSAb‐positive samples. (b) The triangles TBAb measured in the TBAb bioassay (cut‐off at 40% inhibition as a dotted line). [Colour figure can be viewed at wileyonlinelibrary.com].