What is the pathogenesis and management of Hashimoto thyroiditis?

Pathogenesis of Hashimoto Thyroiditis

Hashimoto thyroiditis is an autoimmune disorder characterized by thyroid-specific autoantibodies, lymphocytic infiltration of the thyroid gland, and progressive destruction of thyroid tissue leading to hypothyroidism. 1, 2

Etiopathogenesis

Multifactorial Origin

• Genetic factors: HLA associations play a significant role in predisposing individuals to Hashimoto thyroiditis 3
• Environmental triggers: Iodine supply, infections, and stress can trigger immune modulation 3
• Epigenetic influences: Contribute to disease development 2

Immunological Mechanisms

1. Cellular immunity:

   • T-cell infiltration into the thyroid gland
   • Formation of lymphoid follicles with germinal centers
   • Lymphoplasmacytic infiltration causing progressive damage

2. Humoral immunity:

   • Production of autoantibodies against thyroid antigens:
     • Thyroid peroxidase (TPO) antibodies
     • Thyroglobulin (Tg) antibodies
   • These antibodies serve as diagnostic markers and contribute to thyroid damage

3. Histopathologic features:

   • Lymphocytic infiltration of the thyroid gland
   • Lymphoid follicle formation with germinal centers
   • Parenchymal atrophy
   • Presence of Hürthle cells (oxyphilic cells) - follicular cells rich in mitochondria 2, 4

Disease Progression

1. Initial phase:

   • Immune-triggered lymphocytic infiltration begins
   • Patients may be euthyroid or even experience transient hyperthyroidism (Hashitoxicosis)

2. Progressive phase:

   • Continued destruction of thyroid tissue
   • Thyroid gland may initially enlarge (goiter) due to inflammation
   • Eventually shrinks as destruction progresses

3. End stage:

   • Development of permanent hypothyroidism as thyroid tissue is destroyed
   • Requires lifelong thyroid hormone replacement therapy 1, 5

Clinical Variants

Hashimoto thyroiditis encompasses several clinical variants:

• Classic form (lymphocytic goiter)
• Fibrous variant
• IgG4-related variant
• Juvenile form
• Hashitoxicosis
• Painless thyroiditis (sporadic or post-partum) 4

Associated Conditions

Hashimoto thyroiditis frequently coexists with other autoimmune disorders:

• Thyroid disorders are the most common concurrent autoimmune disease in patients with autoimmune hepatitis (10.5%) 6
• Patients should be screened for other autoimmune conditions such as adrenal insufficiency 1
• Metabolic disorders are common even in euthyroid patients with Hashimoto thyroiditis 7

Diagnostic Approach

1. Laboratory testing:

   • Elevated TPO and Tg antibodies
   • TSH, Free T4, and Free T3 measurements to assess thyroid function
   • Initially normal or elevated TSH with progression to overt hypothyroidism

2. Imaging:

   • Thyroid ultrasound showing reduced echogenicity
   • Evaluation for nodules or goiter

3. Cytological examination:

   • Lymphocytic infiltration
   • Presence of Hürthle cells 1, 4

Management

1. Thyroid hormone replacement:

   • Levothyroxine is the mainstay of treatment
   • Initial dose: 1.0-1.5 μg/kg/day
   • Dose adjustments in 12.5-25 μg increments until TSH normalizes
   • Target TSH between 0.5-1.5 mIU/L 1

2. Monitoring:

   • Every 4-6 weeks until stable, then annually
   • Patients with elevated TPO antibodies >500 IU/ml should be monitored every 6-12 months even with normal TSH 1

3. Nutritional considerations:

   • Evaluation and correction of common deficiencies:
     • Vitamin D
     • Selenium
     • Magnesium
     • Iron
     • Vitamin B12 7

4. Special circumstances:

   • Pregnancy: Increase levothyroxine dosage by 30%, monitor TSH monthly
   • Elderly patients: More likely to progress to overt hypothyroidism, require more aggressive monitoring 1

Hashimoto thyroiditis remains a complex autoimmune disorder with evolving understanding of its pathogenesis, requiring ongoing surveillance and appropriate management to prevent complications and maintain quality of life.