What causes autoimmune thyroiditis?

Causes of Autoimmune Thyroiditis

Autoimmune thyroiditis is caused by a complex interaction of genetic susceptibility, environmental factors, and immune dysregulation that leads to loss of immunological tolerance and subsequent autoimmune attack on thyroid tissue.

Genetic Factors

• Genetic predisposition plays a significant role in autoimmune thyroiditis development, with specific HLA associations (HLA-DR/DQ alleles) that can be either predisposing or protective 1
• Family history of autoimmune disorders increases risk, as autoimmune thyroiditis often clusters with other autoimmune conditions 1
• Genome-wide association studies have identified specific loci associated with autoimmune disorders, including genes involving barrier integrity and immune function 1

Environmental Triggers

• Excess dietary iodine is the best-established environmental trigger for autoimmune thyroiditis in genetically susceptible individuals 2
• Infections may trigger autoimmunity through molecular mimicry, where viral or bacterial peptides activate T cells specific for thyroid antigens 1
• Environmental chemicals and pollutants that affect thyroid function or promote immune dysfunction include 2:
  • Polyaromatic hydrocarbons
  • Polybrominated biphenols
  • Polychlorinated biphenols
• Certain medications can induce thyroid autoimmunity, particularly immune checkpoint inhibitors used in cancer treatment 1

Immunological Mechanisms

• Loss of immunological tolerance leads to an autoimmune attack against thyroid tissue 3
• Cellular immunity involves:
  • T-cell infiltration of the thyroid gland 3
  • Proinflammatory cytokine production 4
• Humoral immunity involves:
  • Production of thyroid-specific autoantibodies, primarily against thyroid peroxidase (TPO) and thyroglobulin (Tg) 4
  • Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis 1

Pathophysiological Process

• Lymphocytic infiltration of the thyroid gland, especially T cells, is the histological hallmark 3
• Progressive destruction of thyroid follicles leads to gradual atrophy and fibrosis 3
• Initial phase may involve release of stored thyroid hormones causing transient hyperthyroidism 5
• Continued destruction leads to hypothyroidism as the thyroid loses functional capacity 5

Associated Conditions

• Autoimmune thyroiditis frequently coexists with other autoimmune disorders 1:
  • Type 1 diabetes mellitus (17-30% of patients with type 1 diabetes have thyroid autoantibodies) 1
  • Celiac disease 1
  • Autoimmune hepatitis 1
  • Systemic lupus erythematosus 1
  • Rheumatoid arthritis 1
  • Sjögren syndrome 1

Clinical Implications

• Autoimmune thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas 3
• Hashimoto's thyroiditis affects approximately 20-30% of the general population 3
• Women are more frequently affected than men 5
• Diagnosis is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound findings, and sometimes histological features 5
• Treatment primarily involves thyroid hormone replacement therapy to achieve euthyroidism 5

Preventive Considerations

• While genetic factors cannot be modified, addressing modifiable environmental triggers may help reduce risk in susceptible individuals 2
• Appropriate iodine intake (avoiding both deficiency and excess) is important 2
• Regular monitoring for thyroid dysfunction is recommended in patients with other autoimmune conditions 1