Endocrine Abstracts

Introduction: Graves’ disease (GD), an autoimmune disorder characterized by hyperthyroidism and thyroid eye disease (TED), presents a multifaceted challenge in understanding its pathogenesis and developing effective treatments. The decision to conduct this analysis stems from a notable observation in our mouse model of GD/TED. Despite observing substantial alterations in the thyroid gland and orbit, we consistently encounter challenges in demonstrating significantly increased levels of thyroxine (T4), a hallmark of hyperthyroidism. This study aimed to elucidate the relationship between thyroid hormones and liver gene expression, focusing on thyroxine (T4), triiodothyronine (T3), and key liver genes involved in thyroid hormone metabolism, including deiodinase 1 (Dio1) and Thyroxine-binding Globulin (Serpina7).

Methods: Mice were divided into two groups: one immunized with the TSHR A-subunit to induce Graves’ disease and the other with a control plasmid, ß-Gal, for comparison. Serum levels of total T4 (TT4), free T3 (FT3), and free T4 (FT4) were measured to evaluate thyroid function. Additionally, expression levels of Dio1 and Serpina7 in liver tissues were assessed to investigate their involvement in thyroid hormone metabolism. Histological examination was conducted on thyroid glands to assess hyperthyroidism and on orbits to evaluate TED pathology.

Results: Analysis revealed significant alterations in thyroids, orbits, and thyroid hormone levels in TSHR-immunized mice compared to controls, with elevated but not statistically significant TT4 and FT4 levels and altered FT3 levels. Dysregulated expression of Dio1 and Serpina7 in the livers of TSHR mice indicated disruptions in thyroid hormone metabolism. These findings suggest a potential association between thyroid hormone dysregulation and liver gene expression in TED pathogenesis.

Conclusion: Understanding the intricate interplay between thyroid hormones and liver gene expression in our GD/TED mouse model may offer insights into disease mechanisms and therapeutic targets. Targeting liver genes involved in thyroid hormone metabolism could represent a novel approach for managing Graves’ disease and associated complications, including thyroid eye disease. However, the main result of this study is that we were able to show that our mouse model works and that the mice show pronounced hyperthyroidism and TED symptoms despite different T4 levels.