Radiation plays a significant and complex role in the development and progression of autoimmune thyroiditis, a condition where the immune system mistakenly attacks the thyroid gland. This role involves multiple biological mechanisms, including direct tissue damage, immune system activation, and the triggering of autoimmune responses.
When the thyroid gland is exposed to radiation—whether from medical treatments like radiotherapy, environmental exposure, or accidental events—the radiation causes damage at the cellular and molecular levels. This damage includes destruction of thyroid cells (parenchymal cells), vascular injury, and DNA damage such as double-strand breaks. These effects lead to the release of cellular components and molecules known as damage-associated molecular patterns (DAMPs). DAMPs act as distress signals that alert the immune system to tissue injury.
The immune system responds to these signals by activating antigen-presenting cells (APCs) such as dendritic cells. These cells process and present thyroid antigens—proteins from the damaged thyroid cells—to T cells, which are key players in adaptive immunity. This activation can lead to a heightened immune response against thyroid tissue, sometimes breaking the immune system’s tolerance to self-antigens and initiating or exacerbating autoimmune thyroiditis.
Radiation also induces inflammation in the thyroid gland. Initially, this inflammation is acute, characterized by immune cell infiltration and the release of proinflammatory cytokines such as interleukins and interferons. Over time, this can progress to chronic inflammation, which sustains immune activation and tissue damage. The inflammatory environment further promotes the recruitment and activation of immune cells that target the thyroid, perpetuating the autoimmune process.
Another important aspect is that radiation can alter the balance of immune cell types within the thyroid. For example, macrophages may polarize toward a proinflammatory M1 phenotype, secreting cytokines that amplify inflammation. This shift in immune cell behavior contributes to the persistence and severity of autoimmune thyroiditis.
The dose of radiation plays a crucial role in determining the extent of thyroid damage and autoimmune risk. Higher doses are more likely to cause significant tissue injury and provoke stronger immune responses. However, even lower doses can contribute to autoimmune phenomena in susceptible individuals, especially those with genetic predispositions or pre-existing immune dysregulation.
Radiation-induced autoimmune thyroiditis can manifest clinically as hypothyroidism or, less commonly, hyperthyroidism. The destruction of thyroid tissue reduces hormone production, leading to hypothyroidism, while immune stimulation may sometimes cause transient hyperthyroid phases due to the release of stored thyroid hormones from damaged cells.
In summary, radiation contributes to autoimmune thyroiditis by causing direct thyroid cell injury, releasing danger signals that activate the immune system, inducing inflammatory responses, and disrupting immune tolerance to thyroid antigens. This complex interplay between radiation-induced damage and immune activation underlies the development and progression of autoimmune thyroid disease following radiation exposure.