engleski

Thyroid Stimulating Immunoglobulins in Graves’ disease diagnosis

Background-Aim: Graves’ disease is the most common cause of hyperthyroidism. It is autoimmune disorder caused by the presence of thyroid stimulating immunoglobulins (TSI) that bind to the TSH receptor (TSHR) and mimic Thyroid Stimulating Hormone (TSH) stimulation of the thyroid cells resulting in uncontrolled production of thyroid hormones that leads to hyperthyroidism. TSIs can bind to tissues in the eyeballs and beneath the skin and contribute to the development of Graves’ disease-specific extra thyroidal manifestations of the bulging eyes and pretibial myxedema. In contrast, Thyroid Blocking Immunoglobulins (TBI) binds to the TSHR and inhibits TSH stimulation of thyroid cells, leading to hypothyroidism. Currently, the laboratory diagnosis of Graves’ disease is based on thyroid hormones and TSHR autoantibody (TRAb) measurement. However, TRAb antibodies do not distinguish TSI from TBI, resulting in a certain percentage of poorly diagnosed patients. The aim of the study was to compare the utility of TSI and TRAb tests in the diagnosis of Graves’ disease. Materials and Methods: Our study included 65 female patients with a median age of 50 years (range 20-79), received at the Clinical Institute of Nuclear Medicine and Radiation Protection, University Hospital Centre Osijek, Osijek, Croatia with a clinical manifestation of Graves’ disease. Venous blood for TSH, free thyroxine (fT4), free triiodothyronine (fT3), TRAb and TSI measurement was collected in serum vacutainer tubes and centrifuged at 3500 rpm for 10 min. Serum aliquots were stored at -20 °C until analysis. Levels of TSH, fT4 and fT3 in serum samples were determined retrospectively on the fully automated chemiluminescence immunoassay platform Arhitect i1000SR (Abbott Laboratories, Lake Forest, USA), TRAb on an electrochemiluminescence immunoassay platform Cobas e601 (Roche Diagnostics Ltd. Mannheim, Germany) and TSI on chemiluminescence immunoassay platform Immulite 2000 XPi (Siemens Healthcare Diagnostics Inc., Flanders, USA). Statistical analysis was performed with the MedCalc, Version 12.4.0.0. (Medcalc Software, Mariakerke, Belgium). Results: Based on TSI concentrations, the patients were divided into two groups: 47 with Grave’ disease and 14 with hyperthyreosis of another cause. For TRAb, sensitivity of 87.8% and specificity of 93.7% were calculated by the receiver operating characteristic (ROC) analysis at the limit value of 1.9 U/L and the associated area under the curve (AUC) value of 0.915 (95% CI 0.818- 0.969). At the threshold value defined by the TRAb protocol (>1.75 U/L), positive predictive value was 95% and negative predictive value was 70%. Conclusion: Although TRAb measurement exhibited high specificity and sensitivity in the Graves’ disease diagnosis there are still a certain percentage of poorly diagnosed patients. Since a fast and accurate diagnosis is imperative in order to prescribe the appropriate treatment as soon as possible and improve the patient’s quality of life, the use of TSI measurement can accelerate and facilitate the diagnosis of Graves’ disease and ensure timely therapy.

Graves' disease, TSI, TRAb

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