Question
Pathogenesis and Pathology of Hashimoto’s Thyroiditis
Answer
Pathogenesis: Hashimoto thyroiditis is an organ-specific autoimmune disease and the most common cause of hypothyroidism in iodine-sufficient areas. It results from a breakdown in self-tolerance to thyroid antigens, involving CD8+ cytotoxic T-cell-mediated destruction of thyroid follicular cells, antibody-dependent cell-mediated cytotoxicity, and binding of autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin) that contribute to follicular injury. There is a strong genetic predisposition (associated with CTLA-4 polymorphisms and HLA-DR3/DR5) and it is more common in women.
Pathology:
- Gross: Diffusely, symmetrically enlarged thyroid, intact capsule; pale, grey-tan, firm, somewhat lobulated cut surface.
- Microscopy: Extensive lymphoplasmacytic infiltration with well-developed germinal centres; thyroid follicles are atrophic and lined by Hürthle cells (oxyphil metaplasia — enlarged cells with abundant granular eosinophilic cytoplasm from mitochondrial accumulation); variable interstitial fibrosis (marked in the fibrosing variant).
Clinical course: Presents with painless goitre, often progressing through a transient hyperthyroid phase (“Hashitoxicosis,” from follicular disruption releasing stored hormone) before progressing to permanent hypothyroidism. Associated with a small increased risk of thyroid lymphoma and papillary thyroid carcinoma.