What is autoimmune thyroiditis?

Autoimmune Thyroiditis: Definition and Clinical Overview

Autoimmune thyroiditis is a T cell-mediated organ-specific autoimmune disorder where the immune system attacks the thyroid gland, leading to lymphocytic infiltration of thyroid tissue and progressive destruction of thyroid cells, most commonly manifesting as Hashimoto's thyroiditis with eventual hypothyroidism. 1

Pathophysiology and Immune Mechanism

• The disease results from dysregulation of the immune system causing an autoimmune attack on thyroid tissue, characterized by lymphocytic infiltration of the thyroid parenchyma 1
• Recruited T helper 1 (Th1) lymphocytes produce enhanced IFN-γ and TNF-α, which stimulates CXCL10 secretion from thyroid cells, creating an amplification feedback loop that initiates and perpetuates the autoimmune process 1
• The autoimmune process is characterized by the presence of autoantibodies against thyroid peroxidase (TPO) and thyroglobulin, which serve as diagnostic markers 2

Clinical Presentation and Natural History

• Initial thyroid cell destruction may release stored thyroid hormones into the bloodstream, causing transient hyperthyroid symptoms 3
• As destruction progresses, patients typically transition through euthyroidism before developing chronic hypothyroidism 3
• Ultrasound characteristically shows hypoechogenic and inhomogeneous thyroid parenchyma 2

Epidemiology and Risk Factors

• The disease predominantly affects women and has a prevalence of approximately 5%, though antithyroid antibodies may be present in even higher percentages of the population 1
• Genetic predisposition involves specific HLA associations (HLA-DR/DQ alleles) that can be either predisposing or protective 4
• Family history of autoimmune disorders significantly increases risk, as autoimmune thyroiditis often clusters with other autoimmune conditions 4
• Environmental triggers include infections (which may trigger autoimmunity through molecular mimicry where viral or bacterial peptides activate T cells specific for thyroid antigens) and certain medications, particularly immune checkpoint inhibitors used in cancer treatment 4

Associated Autoimmune Conditions

• Autoimmune thyroiditis frequently coexists with type 1 diabetes mellitus, celiac disease, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome 4, 1
• The disease is often associated with vitiligo, Addison's disease, and diabetes mellitus type 1, frequently presenting as polyglandular autoimmune syndrome type 2 2
• Patients with positive TPO antibodies should be screened for celiac disease (using IgA tissue transglutaminase antibodies with total serum IgA), type 1 diabetes (fasting glucose and HbA1c), Addison's disease (21-hydroxylase antibodies or adrenocortical antibodies), and pernicious anemia (B12 levels) 5

Diagnostic Approach

• Diagnosis is based on clinical symptoms, positive anti-thyroid antibodies (particularly anti-TPO and anti-thyroglobulin), ultrasound findings, and histological features when available 3
• TPO antibodies are present in 99.3% of Hashimoto's thyroiditis patients and are more predictive than anti-thyroglobulin antibodies for progression to hypothyroidism 5
• Patients with positive thyroid antibodies have a 4.3% per year risk of developing overt hypothyroidism versus 2.6% per year in antibody-negative individuals 5

Monitoring and Surveillance

• Regular monitoring of thyroid function (TSH and free T4) every 6-12 months is essential in antibody-positive patients, with more frequent monitoring (every 6 months) if TSH is trending upward or symptoms develop 5
• Patients require monitoring for thyroid gland enlargement and the possibility of developing nodular goitre 3
• Extended diagnostic screening for other autoimmune diseases should be conducted both at diagnosis and at regular intervals during follow-up, particularly in patients with HLA DRB1*04:01 or family history of autoimmune disease in first-degree relatives 6

Treatment Principles

• The main goal is correcting hormonal disorders and achieving euthyroidism through thyroid hormone replacement therapy 3
• Treatment with levothyroxine is indicated when TSH rises above 10 mIU/L or if symptoms of hypothyroidism develop 5
• For TSH >10 mIU/L, initiate levothyroxine at approximately 1.6 mcg/kg/day for patients <70 years old without cardiac disease 5
• For patients with cardiac disease or multiple comorbidities and TSH >10 mIU/L, start with 25-50 mcg of levothyroxine and titrate up, monitoring TSH every 6-8 weeks 5
• Prophylactic levothyroxine treatment of euthyroid patients with autoimmune thyroiditis may reduce both serological and cellular markers of autoimmunization 3

Important Clinical Pitfalls

• Avoid testing thyroid function during acute metabolic stress (hyperglycemia, ketosis, weight loss) as results may be misleading due to euthyroid sick syndrome 5
• During acute inflammatory flares, TSH may temporarily decrease due to transient thyrotoxicosis from thyroid cell destruction releasing stored hormone, which can be mistaken for hyperthyroidism but typically transitions to hypothyroidism 5
• TPO antibodies cannot differentiate between hyperthyroid (Graves' disease) and hypothyroid (Hashimoto's) autoimmune thyroid disease, as they are present in 74% of Graves' disease patients 5
• Anti-thyroglobulin antibodies may interfere with thyroglobulin measurement, potentially masking true thyroglobulin levels and complicating monitoring 5