Causes of Hashimoto's Thyroiditis
Hashimoto's thyroiditis is caused by a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation that leads to autoimmune destruction of the thyroid gland.
Genetic Factors
- HLA associations: Strong genetic predisposition linked to specific HLA-DR/DQ genes that can be either predisposing or protective 1
- Sex-related factors: Women are affected 7-10 times more frequently than men, with X-chromosome inactivation patterns playing a significant role 2
- Family history: Increased risk in individuals with family members who have autoimmune thyroid disorders
Environmental Triggers
Iodine exposure: Excessive iodine intake can trigger autoimmune thyroiditis in genetically susceptible individuals 1, 3
- Highly iodinated thyroglobulin becomes more immunogenic
- Universal salt iodization programs can have a transient effect on increasing incidence
Micronutrient deficiencies:
- Selenium deficiency: Selenoproteins are essential for thyroid function and protection against oxidative stress 3
- Iron deficiency: Impairs thyroid metabolism as thyroid peroxidase (TPO) is a heme-containing enzyme 3
- Vitamin D status: Lower vitamin D levels are observed in Hashimoto's patients, though this may be a consequence rather than a cause 3
Infections: Viral or bacterial infections may trigger autoimmunity through molecular mimicry 4
Stress: Can act as an immune modulator that contributes to disease development 4
Immunological Mechanisms
Loss of self-tolerance: Breakdown of immune tolerance mechanisms leads to autoimmune attack on thyroid tissue 2
Lymphocytic infiltration: T-cell infiltration of the thyroid gland is the histological hallmark 5
Autoantibody production:
- Thyroid peroxidase antibodies (TPO-Ab)
- Thyroglobulin antibodies (TG-Ab)
Thyrocyte destruction: Progressive destruction of thyroid follicles leads to gradual atrophy and fibrosis of the gland 5
Associated Autoimmune Conditions
Hashimoto's thyroiditis frequently coexists with other autoimmune disorders 1:
- Addison's disease
- Vitiligo
- Celiac disease
- Autoimmune hepatitis
- Myasthenia gravis
- Pernicious anemia
- Systemic lupus erythematosus (2.8-3% of HT patients)
- Sjögren syndrome (2.8-7% of HT patients)
- Rheumatoid arthritis (2-4% of HT patients)
- Inflammatory bowel disease (2-11.4% of HT patients)
Clinical Implications
The multifactorial etiology explains why Hashimoto's thyroiditis presents with variable clinical courses:
- Initial thyrotoxicosis (Hashitoxicosis) when stored hormones are released from destroyed follicles
- Euthyroid phase when preserved thyroid tissue compensates
- Progressive hypothyroidism as destruction advances
Understanding the causes helps guide monitoring and treatment:
- Assessing iodine, selenium, iron, and vitamin D status
- Screening for other autoimmune conditions
- Monitoring thyroid function regularly
Patients with Hashimoto's thyroiditis have:
- 1.6 times higher risk of papillary thyroid cancer
- 60 times higher risk of thyroid lymphoma compared to the general population 2
The interplay between genetic susceptibility and environmental triggers in Hashimoto's thyroiditis underscores the importance of comprehensive evaluation and management of both thyroid function and associated autoimmune conditions.