When to Order Thyrotropin Receptor Antibody (TRAb) Tests
Thyrotropin receptor antibody (TRAb) tests should be ordered for the diagnosis of Graves' disease, in ambiguous cases of thyrotoxicosis, during pregnancy in women with current or previous Graves' disease, and to predict relapse risk after antithyroid drug therapy. 1, 2
Primary Indications for TRAb Testing
1. Diagnosis of Graves' Disease
- TRAb testing is the primary laboratory test for confirming Graves' disease
- Modern second and third-generation TRAb assays have >95% sensitivity and specificity for Graves' disease 2
- All untreated Graves' disease patients will have positive TRAb (either TSAb and/or TBII) 3
2. Ambiguous Cases of Thyrotoxicosis
- When clinical presentation is unclear between Graves' disease and other causes of thyrotoxicosis:
- Toxic adenoma
- Toxic multinodular goiter
- Subacute thyroiditis
- Lymphocytic thyroiditis 1
3. Pregnancy and Postpartum Management
- In pregnant women with current or previous Graves' disease
- TRAb levels ≥5 IU/L during pregnancy indicate increased risk of:
- Fetal thyrotoxicosis
- Neonatal thyrotoxicosis 2
- Third trimester maternal TRAb levels >7.99 IU/L (4.6 times ULN) predict neonatal thyrotoxicosis with 100% sensitivity and 97.4% specificity 4
4. Predicting Relapse After Treatment
- TRAb levels can guide treatment decisions:
- TRAb >12 IU/L at diagnosis: 60% risk of relapse at 2 years, 84% at 4 years
- TRAb >7.5 IU/L at 12 months of therapy: >90% risk of relapse
- TRAb >3.85 IU/L at cessation of antithyroid drug therapy: >90% risk of relapse 2
5. Management of Graves' Ophthalmopathy
- TRAb levels parallel the course of Graves' ophthalmopathy
- Elevated TRAb indicates need for steroid prophylaxis when radioactive iodine therapy is planned 2
Types of TRAb Tests Available
1. Binding Assays (TBII)
- Measure antibody binding to TSH receptor
- Do not distinguish between stimulating and blocking antibodies
- Widely available in clinical laboratories 5
2. Bioassays (TSAb)
- Measure functional activity of antibodies
- Can distinguish between:
- Stimulating antibodies (TSAb) - cause hyperthyroidism
- Blocking antibodies (TBAb) - can cause hypothyroidism
- More informative but less widely available 5
Clinical Pitfalls and Caveats
Mildly elevated TRAb may occur in transient thyrotoxicosis not due to Graves' disease
- In these cases, TRAb is typically elevated less than twice the upper limit of normal
- Cautious interpretation needed when clinical features of Graves' disease are absent 6
TRAb may be present in some patients with Hashimoto's thyroiditis
- May contribute to hypothyroidism in these patients 5
Serial TRAb measurements during treatment show variable patterns:
- Most patients show parallel decreases in TSAb and TBII during successful treatment
- Persistently elevated TRAb indicates high risk of relapse 3
Very high maternal TRAb levels (>19.06 IU/L or 10.9 times ULN) during pregnancy predict adverse pregnancy outcomes with 100% sensitivity and 93.5% specificity 4
By following these guidelines for TRAb testing, clinicians can improve diagnostic accuracy, predict treatment outcomes, and prevent complications in patients with suspected or confirmed Graves' disease.