Differences Between TSI, TRAB, and TBII in Thyroid Autoimmunity
TSI, TRAB, and TBII are different types of thyroid receptor antibody tests that measure distinct aspects of autoimmune activity against the TSH receptor, with TSI specifically measuring stimulating antibodies, TBII measuring binding inhibition, and TRAB being a general term that encompasses both types of antibodies.
Understanding TSH Receptor Antibodies
Thyroid receptor antibodies (TRAbs) are immunoglobulins that interact with the thyroid-stimulating hormone (TSH) receptor and are primarily associated with Graves' disease. These antibodies can be measured through different assay methods that detect distinct functional properties:
Thyroid-Stimulating Immunoglobulin (TSI)
- Definition: Antibodies that specifically bind to and stimulate the TSH receptor, mimicking the action of TSH
- Mechanism: Activates the TSH receptor, leading to increased thyroid hormone production
- Measurement: Bioassay that measures functional stimulation of the receptor (cyclic AMP production)
- Clinical significance:
Thyrotropin-Binding Inhibitory Immunoglobulin (TBII)
- Definition: Antibodies that bind to the TSH receptor and block TSH binding
- Mechanism: Measures the capacity of antibodies to inhibit binding of labeled TSH to its receptor
- Measurement: Competitive binding assay (receptor assay)
- Clinical significance:
- Less specific for Graves' disease (86% sensitivity, 94.1% specificity) 1
- Does not distinguish between stimulating and blocking antibodies
- May be positive in both hyperthyroidism and hypothyroidism
Thyroid Receptor Antibody (TRAB)
- Definition: General term encompassing all antibodies targeting the TSH receptor
- Includes: Both stimulating (TSI) and blocking antibodies
- Measurement: Various assays that detect binding to the TSH receptor
- Clinical significance:
- Used as a general term for antibodies against TSH receptor
- In clinical practice, often used interchangeably with TBII tests
Clinical Applications and Performance
Diagnostic Accuracy
- Both TSI and TBII assays show strong positive correlation (rs = 0.844) 2
- Combined TSI and TBII assays confirm Graves' disease diagnosis in 79% of cases 2
- TSI bioassay has superior sensitivity for diagnosing Thyroid Eye Disease compared to TBII 1
Monitoring Disease Activity
- Serial changes in TSI and TBII can reflect clinical course of Graves' disease 3
- Patients with persistent high levels of both TSI and TBII during treatment are more likely to experience continued hyperthyroidism 3
- Disappearance of both antibodies is associated with disease remission 3
Potential Pitfalls
- False positive results can occur:
- False negative results are associated with:
- Subclinical hyperthyroidism
- Normal radionuclide uptake
- Longer duration of thyrotoxicosis
- Absence of goiter or Graves' ophthalmopathy 2
Practical Considerations
Test Selection
- For initial diagnosis of suspected Graves' disease:
- TSI bioassay offers highest sensitivity and specificity
- TBII assay is more widely available and provides good diagnostic accuracy
- For monitoring treatment response:
- Both TSI and TBII can be useful
- Changes in antibody levels may predict clinical outcomes
Interpretation
- Positive TSI strongly suggests Graves' disease
- Positive TBII indicates TSH receptor antibodies but doesn't distinguish between stimulating and blocking types
- Negative results in both tests don't completely exclude Graves' disease in patients with mild or longstanding disease
In conclusion, while these tests measure different aspects of TSH receptor antibody activity, they provide complementary information for diagnosing and monitoring autoimmune thyroid disorders, particularly Graves' disease.