Understanding Thyroid Autoimmunity: A Mini Review on the Role of Stress and Immune Activation

Background: The theory that stress plays a critical role in the pathogenesis of autoimmune thyroid diseases (AITDs) has been proposed for at least a century. However, evidence supporting this hypothesis has only recently come to surface. AITDs, including Hashimoto’s thyroiditis and Graves' disease, result from immune system infiltration, with stress significantly modulating neuro-immune-endocrine responses. Methods: This literature review examines the impact of stress-related immune activation in AITD. It explores how triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), thyroid peroxidase (TPO), and thyroglobulin (Tg) are affected by T and B cell behaviors, cytokine production, sympathetic nervous system (SNS) functions, hypothalamic-pituitary-adrenal (HPA) axis activity, glucocorticoid signaling pathways, glucocorticoid-induced tumor-necrosis-factor-receptor (GITR) proteins, and the Th17/Treg ratio. Results: Sensory stimuli (stress, exercise, and diet) trigger HPA axis and SNS altering cortisol levels affecting TSH signaling and immune responses. Glucocorticoid and catecholamine stimulation impacts immune cell activity by acting on IL-6, IL-10, and IL-17 and other proinflammatory cytokines. Th17/Treg ratio imbalances are exerted by FoxP3 transcription factors and GITR protein expression heightening cytokine behavior and activating B10 cells, driving autoimmunity. CD4⁺, CD8⁺, and B10 cells to elicit attacks on thyroid hormones, receptors, TPO, and Tg proteins. Conclusion: Stress influences AITD development and progression through complex immune pathways. Auto reactivity attacks on thyroid cells may occur as a memory mechanism to chronic stress episodes and desperate measures to reduce intracellular stress. Future research should explore stress questionnaires related to AITD onset and develop integrative body-mind-spirit interventions to mitigate stress-related immune activation.