Endocrine Abstracts

JOINT3139

Autoimmune thyroiditis – background Hashimoto’s thyroiditis is marked by the presence of autoantibodies (ATA) targeting thyroid peroxidase (anti-TPO) or thyroglobulin (anti-Tg), along with immune cell infiltration into the thyroid gland, resulting in chronic inflammation. Together with the impairment of central and peripheral tolerance, autoreactive CD4⁺ and cytotoxic T cells play a crucial role in the pathogenesis and maintenance of the disease. Chronic inflammation ultimately leads to diminished thyroid function and an increase in thyroid-stimulating hormone (TSH) levels. ATA positivity does not necessarily result in hypothyroidism; yet, the clinically insignificant disease is a substantial risk factor for fertility and pregnancy complications even with a functionally intact thyroid gland and normal TSH levels. How infertility is linked to autoimmune thyroiditis – hypotheses Systemic immune disfunction affecting reproductive organs and maternal-fetal tolerance associated with ATAs present at reproductive sites. Relative insufficiency of the thyroid gland during pregnancy characterised by elevated TSH levels, as the thyroid gland fails to meet increasing hormonal demands. Comparisons and results We analyzed the gene expression patterns of total peripheral T cells (polyA, bulk mRNA) from ATA+ infertile euthyroid, ATA+ hypothyroid patients, and age-matched healthy controls (three individuals in each group). In the hypothyroid group, NF-κB, p53, TNF, cell proliferation, IL-17 signaling and migratory pathways were upregulated compared to both ATA+ euthyroid and healthy individuals, and members of the CXC chemokine subfamily exhibited elevated expression alongside inflammatory cytokines, such as IL-1α, IL-1β. Euthyroid ATA+ individuals showed no relevant alterations in their T cell gene expression profile relative to the healthy group, suggesting that discernible functional differences at the level of T cells emerge only when the thyroid gland is compromised, and fertility issues most likely have an underlying cause that is not necessarily present at T cell gene expression levels. Furthermore, while the impacted pathways were largely analogous in comparison of the hypothyroid vs. healthy, as well as between the hypothyroid vs. euthyroid ATA+ groups, minor differences were noticeable, including the HIF1 signaling pathway, indicating a transition to anaerobic metabolism only subsequent to thyroid dysfunction.