When to check TRAB (TSH receptor antibody) and anti-TPO (anti-thyroid peroxidase antibody) tests?

When to Check TRAb and Anti-TPO Antibodies

Check anti-TPO antibodies at the time of thyroid dysfunction diagnosis to identify autoimmune etiology, and check TRAb specifically when evaluating thyrotoxicosis to diagnose Graves' disease or when monitoring pregnant patients with current or past Graves' disease for fetal risk. 1, 2

Anti-TPO Testing Indications

Initial Diagnostic Scenarios

• Measure anti-TPO when TSH is elevated (above 6.5 mU/L) to confirm autoimmune thyroiditis as the cause of hypothyroidism 1
• Test at diagnosis of type 1 diabetes in children and adolescents, as 17-30% will have thyroid autoantibodies, with anti-TPO being more predictive than anti-thyroglobulin antibodies 1
• Check in patients with unexplained symptoms of hypothyroidism (fatigue, weight gain, hair loss, cold intolerance, constipation, depression) even when TSH is normal, as positive antibodies predict future dysfunction 1, 3

High-Risk Populations Requiring Screening

• Postpartum women should be evaluated when symptoms suggest thyroid dysfunction 1
• Elderly patients warrant testing given higher prevalence of thyroid disease 1
• Patients with Down syndrome require screening due to increased autoimmune thyroid disease risk 1, 4
• Individuals with other autoimmune conditions (type 1 diabetes, celiac disease, Addison's disease) should be screened for thyroid autoimmunity 1, 3

Monitoring After Initial Positive Result

• Recheck TSH every 1-2 years if anti-TPO is positive but thyroid function remains normal, as these patients have 4.3% annual risk of developing overt hypothyroidism versus 2.6% in antibody-negative individuals 1, 3
• Test more frequently (every 6 months) if TSH is trending upward or symptoms develop 3

TRAb Testing Indications

Differential Diagnosis of Thyrotoxicosis

• Measure TRAb in all patients with thyrotoxicosis (suppressed TSH with elevated free T4 or T3) to distinguish Graves' disease from other causes 2, 5
• Positive TRAb (>94% sensitivity) confirms Graves' disease, while negative result with imaging supports toxic nodular goiter or thyroiditis 2, 6
• Check TRAb in euthyroid or hypothyroid patients with eye disease suspicious for Graves' ophthalmopathy 2, 5

Pregnancy-Related Testing

• Test all pregnant women with current or past Graves' disease to assess fetal and neonatal thyrotoxicosis risk, as TRAb crosses the placenta 2, 5
• Measure TRAb in third trimester even if mother is euthyroid on treatment, as antibodies can affect fetal thyroid 2

Treatment Monitoring in Graves' Disease

• Check TRAb at time of antithyroid drug withdrawal (typically after 12-18 months of therapy) to predict remission likelihood 2, 6
• Persistently elevated TRAb at withdrawal indicates high relapse risk and may guide decision for definitive therapy (radioiodine or surgery) 2, 6
• TRAb levels decline significantly during treatment (64% positive after 6 months, 86.7% normal after treatment completion), unlike anti-TPO which remains elevated 6

Common Pitfalls to Avoid

Timing and Interpretation Issues

• Do not check thyroid antibodies during acute metabolic stress (diabetic ketoacidosis, severe hyperglycemia, acute illness) as thyroid function tests may show euthyroid sick syndrome and be misleading 1, 3
• Wait until metabolic stability is achieved before testing, particularly in newly diagnosed diabetes 1, 3
• Recognize that anti-TPO remains elevated for years even after successful treatment or thyroidectomy (92.3% still positive 2 years post-surgery), so it cannot be used to monitor treatment response 6

Clinical Context Considerations

• Do not use anti-TPO alone to diagnose hyperthyroidism—it is elevated in 88.6% of Graves' disease but does not distinguish from Hashimoto's thyroiditis (100% positive) 6
• Remember that anti-thyroglobulin antibodies can interfere with thyroglobulin measurement in thyroid cancer monitoring 3, 7
• Consider that 12.5% of Hashimoto's patients may have low-level TRAb positivity, but median values are much lower than in Graves' disease (4.1 U/L vs 52 U/L) 6

Screening for Associated Conditions

• When anti-TPO is positive, screen for other autoimmune diseases: check fasting glucose/HbA1c for type 1 diabetes, IgA tissue transglutaminase for celiac disease, and consider 21-hydroxylase antibodies for Addison's disease 3
• In children with type 1 diabetes and positive thyroid antibodies, monitor for subclinical hypothyroidism which increases hypoglycemia risk and may impair growth 1, 3