What is the role of TSI (Thyroid Stimulating Immunoglobulin) and TBII (Thyrotropin Binding Inhibitory Immunoglobulin) antibody testing in the diagnosis and treatment of Graves' disease?

Role of TSI and TBII Antibody Testing in Graves' Disease Diagnosis and Treatment

TSI and TBII antibody testing are highly valuable diagnostic tools for Graves' disease, with both tests showing excellent sensitivity and specificity, though the combination of both tests offers little additional benefit compared to TBII testing alone. 1

Diagnostic Value

Accuracy and Performance

• Third-generation TSI bioassay and TBII assays demonstrate strong correlation (rs = 0.844) with 88% concordance in patients with thyrotoxicosis 1
• Both tests show high sensitivity and specificity for diagnosing Graves' disease:
  • Combined TSI and TBII testing confirms Graves' disease in 79% of cases and excludes it in 92.5% of non-Graves' cases 1
  • TBII testing alone shows similar accuracy (77.5%) to the combined approach (81.4%) 1
  • When using both tests, virtually all untreated Graves' patients (100%) show positivity in at least one test 2

Cutoff Values and Interpretation

• Optimal cutoff values based on ROC analysis:
  • TSI: 150% (above this indicates positivity)
  • TBII: 10% inhibition 2, 3
• False negatives are more common in patients with:
  • Subclinical hyperthyroidism
  • Normal radionuclide uptake
  • Longer duration of thyrotoxicosis
  • Absence of goiter or Graves' ophthalmopathy 1

Clinical Applications

Initial Diagnosis

• TRAb testing (either TSI or TBII) should be considered in patients with thyrotoxicosis to differentiate Graves' disease from other causes
• The human recombinant TBII assay (hTBII) demonstrates higher sensitivity (87%) compared to conventional porcine TBII assay (52%) 3
• In cases where clinical features are ambiguous, antibody testing can provide valuable diagnostic information

Treatment Monitoring and Prognosis

• Serial measurements of TSI and TBII during antithyroid drug therapy help predict clinical outcomes:
  • Decreasing and eventually disappearing antibody levels correlate with remission 2, 4
  • Persistently elevated antibody levels suggest ongoing disease activity and higher risk of relapse 2, 4
• TBII positivity during remission may predict relapse, with studies showing relapse in 3 of 7 TBII-positive patients within 6 months 3

Important Considerations and Pitfalls

False Positives

• Positive TRAb results can occur in patients with transient thyrotoxicosis who don't have Graves' disease 5
• Mildly elevated TRAb results (less than twice the upper limit of normal) should be interpreted cautiously in patients without pathognomonic evidence of Graves' disease 5

False Negatives

• Negative antibody tests don't rule out Graves' disease, particularly in:
  • Mild disease
  • Long-standing disease
  • Subclinical hyperthyroidism 1

Test Selection

• While both tests are valuable, TBII testing alone appears to provide similar diagnostic accuracy to the combined approach 1
• The human recombinant TBII assay offers superior sensitivity compared to older porcine TBII assays 3
• In cases where TBII is negative but clinical suspicion remains high, adding TSI testing may be beneficial 2

Practical Approach to Testing

1. Initial diagnosis: Order TBII testing as the first-line test for suspected Graves' disease
2. If TBII negative but clinical suspicion high: Consider adding TSI testing
3. During treatment: Monitor antibody levels to assess treatment response and predict remission
4. After treatment discontinuation: Consider antibody testing to help predict relapse risk

Human recombinant TBII assays are preferred over older porcine assays due to their superior sensitivity in detecting low-titer antibodies, which is particularly valuable for monitoring disease activity during and after treatment 3.