What is Hashimoto thyroiditis?

Hashimoto's Thyroiditis

Hashimoto's thyroiditis is the most common autoimmune thyroid disorder and the leading cause of hypothyroidism in industrialized nations, characterized by chronic autoimmune destruction of the thyroid gland that often leads to progressive thyroid dysfunction. 1

Definition and Epidemiology

• An autoimmune disorder affecting the thyroid gland
• Affects women 7-10 times more frequently than men 2
• Most common cause of hypothyroidism in iodine-sufficient regions 3
• Approximately 20-30% of the population with thyroid disorders have Hashimoto's thyroiditis 3

Pathophysiology

Hashimoto's thyroiditis develops through a complex interplay of factors:

1. Autoimmune Mechanism:

   • Cellular and humoral immunity play key roles 4
   • T and B cell inflammatory infiltration of the thyroid gland
   • Production of autoantibodies against thyroid antigens:
     • Thyroid peroxidase antibodies (TPO-Ab)
     • Thyroglobulin antibodies (TG-Ab)

2. Contributing Factors:

   • Genetic susceptibility (strong HLA associations, particularly with HLA-DR/DQ genes) 1
   • Environmental triggers
   • Excessive iodine consumption in genetically susceptible individuals 1
   • X-chromosome inactivation patterns 2
   • Microbiome composition 2

3. Histopathologic Features:

   • Lymphoplasmacytic infiltration
   • Lymphoid follicle formation with germinal centers
   • Parenchymal atrophy
   • Presence of large follicular cells and oxyphilic/Askanazy cells 4

Clinical Presentation

Hashimoto's thyroiditis typically follows a triphasic pattern of thyroid dysfunction 5:

1. Initial hyperthyroid phase (thyrotoxicosis):

   • Due to release of preformed thyroid hormone from damaged thyroid cells
   • May present with palpitations, anxiety, and chest tightness

2. Hypothyroid phase:

   • Occurs when thyroid hormone stores are depleted
   • Common symptoms include:
     • Fatigue
     • Muscle cramps
     • Constipation
     • Cold intolerance
     • Hair loss
     • Voice changes
     • Weight gain
     • Intellectual slowness
     • Insomnia 1

3. Recovery phase (in some cases):

   • Restoration of normal thyroid function
   • Many patients develop permanent hypothyroidism

Associated Conditions

Hashimoto's thyroiditis is frequently associated with other autoimmune disorders 1:

• Other autoimmune thyroid diseases (10-23%)
• Systemic lupus erythematosus (2.8-3%)
• Sjögren syndrome (2.8-7%)
• Rheumatoid arthritis (2-4%)
• Inflammatory bowel disease (2-11.4%)
• Addison's disease
• Vitiligo
• Celiac sprue
• Autoimmune hepatitis
• Myasthenia gravis
• Pernicious anemia

Diagnosis

Diagnosis is based on clinical evaluation and laboratory findings:

1. Laboratory Tests:

   • Thyroid stimulating hormone (TSH) - most sensitive initial screening test 1
   • Free Thyroxine (Free T4) - to distinguish between subclinical and overt hypothyroidism
   • Thyroid antibodies:
     • TPO antibodies - diagnostic marker for autoimmune thyroid disease
     • Thyroglobulin antibodies (TG-Ab) - associated with symptom burden 1

2. Imaging:

   • Thyroid ultrasound - may show heterogeneous echotexture and hypoechogenicity

3. Cytology:

   • Fine needle aspiration may show lymphocytic infiltration 4

Treatment

The standard treatment approach for Hashimoto's thyroiditis depends on the phase:

1. Hyperthyroid Phase:

   • Beta-blockers to manage adrenergic symptoms 5
   • Symptomatic treatment

2. Hypothyroid Phase:

   • Levothyroxine (LT4) oral T4 monotherapy at doses ranging from 1.4 to 1.8 mcg/kg/day based on the degree of preserved thyroid functionality and lean body mass 1, 2
   • Regular monitoring of thyroid function:
     • Every 2-4 weeks until stable during treatment initiation
     • Every 6-12 months once stable 1
     • More frequent monitoring (every 2-4 weeks) in pregnant women 1

Complications and Special Considerations

1. Pregnancy:

   • TPO antibodies are associated with a 2-4 fold increased risk of recurrent miscarriages and preterm birth 2
   • Only levothyroxine is indicated during pregnancy (T3 does not sufficiently cross fetal blood-brain barrier) 2

2. Malignancy Risk:

   • 1.6 times higher risk of papillary thyroid cancer 2
   • 60 times higher risk of thyroid lymphoma compared to general population 2

3. Treatment Challenges:

   • Poor response to therapy despite normal TSH may be due to:
     • Comorbidities (other autoimmune diseases, psychiatric disorders)
     • Vitamin and trace element deficiencies
     • Pharmacogenomic and pharmacokinetic factors affecting levothyroxine bioavailability 6

Monitoring

• Regular follow-up is essential to monitor for changes in thyroid function
• Lifelong surveillance is typically required for patients with permanent hypothyroidism