Which autoantibody is most specific for Hashimoto thyroiditis and correlates with disease severity?

Explanation

## Autoantibodies in Hashimoto Thyroiditis **Key Point:** Anti-TPO (thyroid peroxidase) antibodies are the most specific and most frequently detected autoantibodies in Hashimoto thyroiditis, present in >90% of patients. They correlate with disease severity and progression to hypothyroidism. ### Autoantibody Profile in Hashimoto | Antibody | Frequency | Specificity | Clinical Significance | | --- | --- | --- | --- | | **Anti-TPO** | >90% | Very high for Hashimoto | Correlates with severity; predicts hypothyroidism | | **Anti-thyroglobulin** | 60–70% | Moderate | Often coexists with anti-TPO; less specific | | **Anti-TSH receptor (TRAb)** | <5% | Specific for Graves | Absent in Hashimoto; defines Graves disease | | **Anti-smooth muscle** | Rare | Non-specific | Seen in other autoimmune diseases | **High-Yield:** Anti-TPO is the **single most useful diagnostic antibody** for Hashimoto. Its presence in a patient with hypothyroidism and elevated TSH confirms autoimmune thyroiditis. Anti-thyroglobulin may also be present but is less specific. ### Mechanism of Anti-TPO Pathogenicity 1. **Antibody-dependent cellular cytotoxicity (ADCC):** Anti-TPO binds to TPO on thyroid follicular cells 2. **Complement activation:** Leads to thyroid cell lysis 3. **T-cell-mediated immunity:** CD8+ T cells directly destroy TPO-expressing cells 4. **Result:** Progressive follicular destruction → hypothyroidism **Clinical Pearl:** A patient with elevated anti-TPO but normal TSH and free T~4~ has **subclinical autoimmune thyroiditis** — they are at high risk for future overt hypothyroidism and should be monitored annually. **Mnemonic:** **TPO = Thyroid Peroxidase Overactive** (in Hashimoto, the immune system attacks TPO, the enzyme that iodates tyrosine residues in thyroglobulin).