An update on the pathogenesis of Hashimoto's thyroiditis

Area of Science:

• Immunology
• Endocrinology
• Genetics

Background:

• Hashimoto's thyroiditis (HT) is a major cause of autoimmune hypothyroidism.
• Noel Rose's foundational work 70 years ago elucidated autoimmune thyroiditis.
• Understanding HT's etiology and pathogenesis remains critical for patient management.

Purpose of the Study:

• To review recent advancements in understanding the causes and pathogenesis of Hashimoto's thyroiditis over the past five years.
• To honor the contributions of Noel Rose to the field of autoimmune thyroid disease.

Main Methods:

• Review of recent genetic studies on HT heritability and associated diseases.
• Analysis of environmental factors, including drug-induced immune modulation.
• Examination of pathogenetic mechanisms involving cytokine networks and T regulatory cells.
• Investigation of disease associations and persistent symptoms in HT patients.

Main Results:

• First-time heritability estimates for HT reveal complex genetic factors, including monogenic forms.
• Environmental factors, particularly immunomodulatory drugs, are increasingly recognized.
• Inflammasome activation and defects in T regulatory cells contribute to loss of self-tolerance.
• New disease associations with HT identified, with potential clinical significance.

Conclusions:

• Recent research has significantly expanded the understanding of HT's complex genetic and environmental underpinnings.
• Pathogenetic mechanisms involve intricate cytokine networks and immune regulatory defects.
• The autoimmune process itself may contribute to persistent symptoms in some levothyroxine-treated HT patients.