Hashimoto's Thyroiditis Beyond Thyroid Hormones: A Systematic Review of Autoimmunity, Inflammation, and Multidimensional Burden

Background: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease. Although levothyroxine therapy effectively normalizes thyroid-stimulating hormone (TSH) in most patients, persistent symptoms are frequently reported, suggesting that autoimmunity and inflammation contribute to reduced quality of life (QoL) independently of thyroid hormone levels. Methods: According to PRISMA guidelines, we systematically searched for MEDLINE, Scopus, and Web of Science studies that assessed the association of thyroid autoimmunity, inflammatory markers, and QoL in adults with HT. Included designs were observational, interventional, and longitudinal studies that published qualified QoL outcomes and immune/inflammatory markers. Results: Across diverse study designs, HT patients-typically euthyroid or receiving long-term levothyroxine therapy-consistently reported lower QoL compared with controls, particularly in cognitive, affective, and vitality domains. Elevated anti-thyroid antibodies (anti-TPO, anti-Tg) were negatively correlated with QoL, whereas TSH and thyroid hormone levels showed no consistent association. Interventional studies demonstrated that total thyroidectomy or therapies associated with reduced antibody titers were accompanied by improvements in fatigue and QoL. However, an important caveat must be emphasized. Some studies did not confirm a direct association between antibody levels and symptom severity, likely reflecting methodological variability and heterogeneity in QoL assessment tools. Conclusion: There is evidence that HT exerts a multidimensional impact beyond endocrine dysfunction, with chronic autoimmunity and low-grade inflammation contributing to impaired QoL. These findings should be taken into account and perhaps challenge a purely TSH-centric model and call for a broader, patient-centered approach that integrates immunological, psychological, and subjective outcomes. Properly designed longitudinal and interventional trials are required to establish causal pathways and support the personalization of therapy.