The Free Thyroxine-to-Thyroid Stimulating Hormone Ratio: A Potential Diagnostic Marker for Graves’ Disease

Abstract

Background: Graves' disease (GD) is a leading cause of hyperthyroidism, characterized by excessive thyroid hormone production. Although the thyroid stimulating hormone receptor autoantibodies (TRAb) test is specific for GD, its limited accessibility often delays diagnosis and treatment, leading to potential complications. Thus, exploring alternative diagnostic markers, such as thyroid hormone ratios, may offer a feasible solution. Objectives: This study aims to assess the diagnostic accuracy of the free thyroxine-to-thyroid stimulating hormone (FT4/TSH) ratio in distinguishing GD from other non-Graves’ disease (NGD) hyperthyroidism. Methods: A retrospective study was conducted at Hospital Raja Perempuan Zainab II in Kelantan, Malaysia, from 2021 to 2023. A total of 351 hyperthyroid patients who underwent initial TRAb testing during this period were included. These patients were categorized into two groups: Graves' disease and NGD hyperthyroidism, based on definitive diagnoses made by endocrinologists, as documented in the electronic medical records. Data on patients' TSH, FT4, and FT4/TSH ratios and TRAb results were retrieved from the laboratory information system (LIS) for analysis. The diagnostic accuracy of these parameters was assessed using receiver operating characteristic (ROC) curve analysis to determine optimal cut-off values, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). Results: Patients with GD had significantly higher FT4 and FT4/TSH ratios and lower TSH levels than NGD hyperthyroid patients (P < 0.001). Receiver operating characteristic analysis identified an FT4/TSH ratio cut-off of 13948.98 pmol/mIU, yielding a specificity of 99.4%, PPV of 92.31%, and an area under the curve (AUC) of 0.740. Conclusions: The FT4/TSH ratio shows promise as an accessible diagnostic marker for GD, particularly where TRAb testing is limited. Its high specificity and PPV could facilitate timely diagnosis, improving patient management and outcomes. Further studies are needed to validate this approach in larger populations.