Rapid and sensitive bioassay for thyroid-stimulating immunoglobulin detection in thyrotropin-binding inhibitory immunoglobulin-negative euthyroid Graves' orbitopathy.

OBJECTIVE: Graves' orbitopathy (GO) typically occurs in hyperthyroid patients with detectable thyroid-stimulating hormone (TSH) receptor antibodies (TSH-R-Ab). Rarely, it presents in euthyroid patients without detectable TSH-R-Ab, as determined by thyrotropin-binding inhibitory immunoglobulin (TBII) assays, posing a diagnostic challenge. While functional bioassays improve TSH-R-Ab detection in euthyroid GO (EGO), their complexity limits clinical use. A novel, highly sensitive bioassay (Turbo TSI) offers a faster and simplified protocol. In this study, we explore Turbo TSI in TBII-negative EGO and compare it to 2 distinct types of binding immunoassays. Furthermore, we describe a large cohort and compare clinical characteristics to hyperthyroid GO patients.

METHODS: Clinical features, thyroid function, and TBII levels of 20 cases were recorded retrospectively. If available, biobank serum was used to reassess TSH-R-Ab levels with Turbo TSI bioassay and bridge-based TSI binding immunoassay. TBII-negative EGO patients were compared to 40 hyperthyroid GO controls.

RESULTS: All cases were TBII-negative and euthyroid at presentation. From 6 patients, biobank serum was available. Two of these sera were found positive with bridge-based TSI binding immunoassay. In contrast, all 6 sera were found positive with the Turbo TSI bioassay. Compared to hyperthyroid GO, TBII-negative EGO patients presented unilaterally/asymmetrically more often, had a milder and less active phenotype, and required less surgical intervention.

CONCLUSIONS: TSH-R-Ab are not absent in TBII-negative EGO, but require highly sensitive bioassays for detection. In contrast to traditional bioassays, Turbo TSI offers a simple and fast protocol and can therefore facilitate diagnosis in these patients. Euthyroid GO presents with a milder phenotype than hyperthyroid GO.