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Antibodies to thyroid peroxidase (Anti-TPO)
(Thyroid Peroxidase Antibodies – Autoimmune Thyroid Disease Marker)
Synonyms
- Anti-TPO
- Thyroid Peroxidase Antibody (TPOAb)
- Microsomal Antibody (old name)
- Anti-Microsomal Antibody
- Thyroid Autoantibody
Units of Measurement
- IU/mL (International Units per milliliter)
- kIU/L (kilo–International Units per liter)
(Most laboratories use IU/mL, while kIU/L is simply IU/mL × 1.)
Description
Anti-TPO antibodies are autoantibodies directed against the enzyme thyroid peroxidase (TPO), which is essential for:
- Iodide oxidation
- Iodination of tyrosine residues
- Coupling reactions to form T3 & T4
High Anti-TPO levels indicate autoimmune thyroid disease, especially:
- Hashimoto thyroiditis (90–95% positive)
- Graves disease (70–80% positive)
Anti-TPO antibodies may appear years before clinical hypothyroidism and are used in both diagnosis and risk prediction.
Physiological Role of TPO
TPO is the key enzyme for thyroid hormone synthesis:
- Oxidizes iodide → iodine
- Iodinates thyroglobulin tyrosine residues
- Couples MIT & DIT → T3 and T4
Autoantibodies interfere with these processes → thyroid hormone deficiency.
Clinical Significance
Elevated Anti-TPO
Seen in:
1. Hashimoto Thyroiditis (Primary Hypothyroidism)
- Anti-TPO positive in ~95%
- Strong association with progressive hypothyroidism
- Even normal TSH + high Anti-TPO = future risk of hypothyroidism
2. Graves Disease
- Found in 70–80%
- Helps differentiate autoimmune hyperthyroidism
3. Postpartum Thyroiditis
- High TPOAb in pregnancy → risk of postpartum thyroid dysfunction
- Predicts hypothyroidism in 6–12 months postpartum
4. Other Autoimmune Conditions
- Type 1 diabetes
- Celiac disease
- Rheumatoid arthritis
- SLE
- Pernicious anemia
5. Euthyroid Women (Risk Marker)
Presence of TPOAb increases risk of:
- Future hypothyroidism
- Pregnancy complications (miscarriage, preterm birth)
Normal / Low Anti-TPO
- Does not exclude autoimmune thyroiditis completely
- High suspicion: combine with Anti-TG, TSH, ultrasound
Reference Intervals
(Tietz 8E + ATA 2016 + Mayo + ARUP)
Reference ranges vary by assay.
Typical Reference Range
- < 35 IU/mL → Negative
- 35–100 IU/mL → Mild elevation
- >100 IU/mL → Strongly positive
- >300–500 IU/mL → Highly suggestive of autoimmune thyroiditis
- >1000 IU/mL → Often indicates active Hashimoto’s; risk of hypothyroidism high
Pregnancy
Anti-TPO positive pregnant women are:
- 3–5× more likely to develop postpartum thyroiditis
- At higher risk of miscarriage and preterm birth
Diagnostic Uses
1. Autoimmune Thyroid Disease
Most sensitive marker of autoimmune thyroiditis.
2. Predicting Hypothyroidism
High TPOAb with normal TSH indicates:
- Future risk of hypothyroidism
- Often treated during pregnancy if TSH >2.5 mIU/L
3. Pregnancy Risk Assessment
Anti-TPO predicts:
- Postpartum thyroiditis
- Pregnancy loss
- Need for closer thyroid monitoring
4. Monitoring Autoimmune Disease Activity
Trends may reflect:
- Autoimmune progression
- Levothyroxine requirement
- Not used alone for treatment decisions
Analytical Notes
- Measured using chemiluminescent immunoassays.
- Biotin supplements (>5 mg/day) cause false results - discontinue 48 hrs before testing.
- Hemolysis and lipemia minimally affect results.
- Units may vary by manufacturer.
Clinical Pearls
- The most sensitive marker of Hashimoto thyroiditis.
- Anti-TPO positivity in euthyroid women warrants annual TSH testing.
- Very high levels do not correlate directly with severity of hypothyroidism.
- Anti-TPO often remains positive for life, even after treatment.
- Anti-TPO + high TSH → treat as autoimmune hypothyroidism.
Interesting Fact
Anti-TPO antibodies were historically called “anti-microsomal antibodies” because they were first detected using thyroid microsomal fractions before the enzyme was identified.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Thyroid Autoantibody Section.
- ATA (American Thyroid Association) 2016 Guidelines - Hypothyroidism & Thyroiditis.
- ESAP Endocrine Reference Ranges - Anti-TPO.
- Mayo Clinic Laboratories - TPO Antibody.
- ARUP Consult - Autoimmune Thyroid Disease Algorithm.
- IFCC - Immunoassay Standardization Guidelines.
- NIH / MedlinePlus - Thyroid Antibody Overview.