rT3 and Inflammation in Hashimoto's Thyroiditis

Hashimoto's thyroiditis (HT) is characterized by an enlarged thyroid gland infiltrated with lymphocytes. The incidence of HT is estimated to be 0.3-1.5 cases per 1000 people, with a female/male predominance of 7-10:1. It has a strong association with other autoimmune diseases. The autoimmune presentation of HT relies on the interaction between environmental factors and genetic background such as human leukocyte antigen (HLA), T lymphocyte-associated 4 (CTLA-4), protein tyrosine phosphatase, non-receptor type 22 (PTPN22) genes, and X chromosome inactivation patterns, leading to an imbalance between self-tolerance mechanisms maintained by regulatory T and B lymphocytes. Furthermore, genetic polymorphisms in self antigens, cytokines and their receptors (e.g., interleukin 2 receptor IL2R), estrogen receptors, adhesion molecules (CD14, CD40), the promoter region of selenoprotein S, and apoptosis-related gene products have been associated with thyroid autoimmunity. Genetic factors account for 70-80% of the risk in the development of Hashimoto's disease, while environmental factors account for 20-30%. HT is diagnosed based on clinical symptoms, antithyroid antibodies, and histological features. Ultrasound imaging of the thyroid gland can aid in differential diagnosis, especially in patients with thyroid peroxidase antibody (TPOAb) negative HT. Ultrasound features of HT include decreased echogenicity, heterogeneity, hypervascularity, and the presence of small cysts. Hashimoto's disease can have stages presenting with hyperthyroidism, euthyroidism, and hypothyroidism. In diagnosis, hyperthyroidism, euthyroidism, and hypothyroidism are determined based on measurements of thyroid-stimulating hormone (TSH), free T4 (sT4), and free T3 (sT3), which are biochemical parameters used.

Hashimoto's thyroiditis is an inflammatory condition affecting the thyroid gland, and patients develop clinical thyroid dysfunction depending on the duration of the disease. HT causes atrophy of the thyroid parenchyma through autoimmune processes and chronic inflammation. This leads to an increase in inflammatory load in patients with Hashimoto's. Studies have shown that inflammation associated with HT may not be limited to the thyroid gland and can trigger a systemic inflammatory process even in patients with normal thyroid function.

Reverse T3 (3,3',5'-triiodothyronine or rT3) is the third most abundant iodothyronine circulating in human blood and is produced by deiodination of the inner ring of the prohormone thyroxine (T4). Unlike the more abundant and active metabolite T3, serum rT3 measurement has not yet found routine clinical application. While rT3 has little effect on nuclear thyroid hormone receptors (THR), it has been shown to interact with more recently identified non-nuclear thyroid hormone receptors. rT3 analysis is useful in confirming the diagnosis of non-thyroid disease syndrome, in measuring the T3/rT3 ratio in insulin-resistant patients, and in hemangiomas where iodothyronine deiodinase type 3 (DIO3) overexpression causes an increase in rT3. rT3 analysis also has the potential to identify situations where the diagnosis of hypothyroidism may be masked by concomitant drug treatment or potentially function as a marker of drug effect.

The aim of this study is to compare rT3 levels in anti-TPO-positive euthyroid Hashimoto's patients with or without thyroid hormone replacement therapy. The impact of drug use on hormone levels in these patient groups will be investigated. Additionally, systemic inflammatory markers derived from the complete blood count will be examined to determine the systemic inflammatory load in these patients.