RESUMO
PURPOSE: Graves' orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO. METHODS: Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively. RESULTS: Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis. CONCLUSIONS: TSH-R-Ab were significantly associated with GO's phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.
Assuntos
Doença de Graves , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/diagnóstico , Estimulador Tireóideo de Ação Prolongada , Autoanticorpos , Imunoglobulinas Estimuladoras da Glândula Tireoide , Receptores da Tireotropina , Tireotropina , FenótipoRESUMO
PURPOSE: Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves' disease and Graves' orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated. METHODS: 91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays. RESULTS: Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (P < 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (P < 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615-9.457, P = 0.003; versus 2.133, 0.904-5.032, P = 0.084, univariate analysis; and OR 4.341, 95%CI 1.609-11.707, P = 0.004; versus 2.337, 0.889-6.145, P = 0.085 multivariate analysis). CONCLUSION: Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.
Assuntos
Autoanticorpos , Doença de Graves , Oftalmopatia de Graves , Imunoglobulinas Estimuladoras da Glândula Tireoide , Autoanticorpos/análise , Autoanticorpos/sangue , Feminino , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/epidemiologia , Doença de Graves/imunologia , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/epidemiologia , Oftalmopatia de Graves/imunologia , Humanos , Imunoensaio/métodos , Imunoglobulinas Estimuladoras da Glândula Tireoide/análise , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Masculino , Pessoa de Meia-Idade , Receptores da Tireotropina/imunologia , Sérvia/epidemiologia , Hormônios Tireóideos/sangueRESUMO
OBJECTIVE: Malignancies and autoimmune thyroid disease are still controversial, but recent studies prove that a long lasting thyroid disease may be linked with malignancy, e.g. papillary thyroid carcinoma in patients with Hashimoto thyroiditis. Having in mind that thyrotropin is a thyroid growth factor, the relationship between its serum values, as well as the levels of anti-peroxidase and anti-thyroglobulin antibodies and thyroid malignancy in patients with nodular thyroid goiter was examined. PATIENTS AND METHODS: Six-hundred-thirty-seven medical records, which included the thyroid fine-needle aspiration cytology were retrospectively evaluated. Patients were grouped regarding the levels of thyrotropin, anti-peroxidase and anti-thyroglobulin antibodies (in or out of the reference ranges) and compared with cytology findings for establishing their prognostic potential for malignancy. RESULTS: Elevated serum thyrotropin (≥ 4.5 mIU/L) was found in 27.3% of patients with thyroid malignancy compared with 10.8% with benign and 16.1% with unspecified cytology finding (p < 0.01). In the group of patients with malignant cytology findings 7.0% of them had elevated anti-peroxidase antibodies level, and 1.4% had anti-peroxidase antibodies level in reference range. In the group of patients with malignant cytology findings 4.2% of them had elevated anti-thyroglobulin antibodies level, and 1.4% had anti-thyroglobulin antibodies level in reference range. CONCLUSIONS: In patients with elevated serum thyrotropin concentration and/or chronic thyroiditis the occurrence of thyroid malignancy is increased.