Hashimoto's Thyroiditis (Chronic Autoimmune Thyroiditis)
The most likely diagnosis is Hashimoto's thyroiditis (chronic autoimmune thyroiditis), given the combination of a diffusely enlarged, firm, nodular, nontender thyroid gland with biochemical hypothyroidism (elevated TSH, low free T4) and positive thyroid autoantibodies. 1
Clinical and Laboratory Profile
The patient presents with the classic triad of Hashimoto's thyroiditis:
Physical examination findings: Diffusely enlarged, firm, nodular, and nontender thyroid gland is the hallmark presentation of chronic lymphocytic thyroiditis 2, 3
Biochemical hypothyroidism: TSH of 6.0 (elevated) with free T4 of 0.8 (low) confirms primary hypothyroidism 1
Positive autoantibodies: Both thyroid peroxidase antibodies (TPO 48) and antithyroglobulin antibodies (Anti-Tg 20) are elevated, confirming autoimmune etiology 1, 2
Normal inflammatory markers: ESR of 15 (normal range) effectively excludes subacute thyroiditis, which typically presents with markedly elevated ESR, thyroid tenderness, and pain 4
Diagnostic Reasoning
Hashimoto's thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas and the most common autoimmune disease overall. 1, 2, 3
The diagnosis relies on three key elements 2, 5:
- Demonstration of circulating thyroid autoantibodies (TPO and/or thyroglobulin antibodies)
- Biochemical evidence of hypothyroidism or thyroid dysfunction
- Compatible clinical features (diffuse goiter with firm, nodular texture)
When two or more of five diagnostic markers are positive (thyroid physical characteristics, autoantibodies, TSH elevation, imaging findings, and thyroid reserve testing), Hashimoto's thyroiditis is the likely diagnosis with 67% accuracy by rule-of-thumb and 88% accuracy by comprehensive evaluation. 5
Key Differentiating Features
The nontender thyroid with normal ESR definitively excludes subacute thyroiditis, which would present with:
- Painful, tender thyroid gland
- Markedly elevated ESR (typically >50 mm/hr)
- Often preceded by viral illness 4
The elevated TSH with low free T4 excludes Graves' disease, which would show:
- Suppressed TSH with elevated free T4
- Presence of TSH receptor antibodies (TRAb)
- Clinical hyperthyroidism 1, 4
Pathophysiology and Natural History
The disease is characterized by 2, 3:
- Lymphocytic infiltration of the thyroid gland, predominantly T cells
- Progressive follicular destruction leading to gradual atrophy and fibrosis
- Loss of immunological tolerance due to genetic susceptibility and environmental triggers
- Transformation of thyroid follicular cells into Hürthle cells (mitochondria-rich cells)
Approximately 20-30% of patients develop Hashimoto's thyroiditis, with women affected more commonly than men. 3
Clinical Significance of Antibody Levels
Elevated thyroglobulin antibodies correlate with symptom burden in Hashimoto's patients, including 6:
- Fragile hair
- Facial edema
- Periorbital edema
- Voice changes
This suggests thyroid autoimmunity plays a direct role in clinical manifestations beyond simple hormone deficiency 6
Management Implications
Treatment consists of daily levothyroxine replacement therapy to correct hypothyroidism. 3
Initial dosing considerations 1:
- For patients under 70 years without cardiac disease: approximately 1.6 mcg/kg/day based on ideal body weight
- For elderly patients (>70 years) or those with cardiac disease: start with 25-50 mcg daily and titrate upward
- Monitor TSH and free T4 every 6-8 weeks until stable, then every 6-12 months
Important Clinical Pitfalls
Surgery is indicated only when 2:
- The goiter causes significant compression of cervical structures (trachea, esophagus)
- Nodular areas cannot be confirmed as benign by fine needle aspiration cytology
- There is concern for concurrent thyroid malignancy (papillary thyroid cancer occurs in approximately 20% of patients with autoimmune thyroiditis) 3
Always screen for associated autoimmune conditions, as approximately 20-30% of patients with Hashimoto's thyroiditis develop other organ-specific or systemic autoimmune disorders 3