What antibody test is used for the assessment of Graves' disease?

Antibody Testing for Graves' Disease Assessment

The TSH receptor antibody (TRAb) test—measured as either thyroid-stimulating immunoglobulin (TSI) or thyrotropin-binding inhibitory immunoglobulin (TBII)—is the definitive antibody test for diagnosing Graves' disease, with both assays demonstrating >95% sensitivity and specificity. 1

Primary Diagnostic Antibody Tests

TRAb Testing (First-Line)

• TSI (thyroid-stimulating immunoglobulin): Bioassay that measures functional stimulation of thyroid cells by patient antibodies 1
• TBII (thyrotropin-binding inhibitory immunoglobulin): Competitive-binding radioreceptor assay that measures inhibition of TSH binding to its receptor 1
• Both assays are equally acceptable for diagnosis, with second- and third-generation TRAb assays achieving >95% sensitivity and specificity 2
• TSI may be slightly more sensitive than TBII (95% vs 85% in untreated hyperthyroid Graves' patients) 3

When to Order TRAb Testing

• Clinical features suggesting Graves' disease: Presence of ophthalmopathy, diffuse goiter, or other pathognomonic features 1
• Ambiguous cases: When distinguishing Graves' disease from other causes of thyrotoxicosis (toxic adenoma, toxic multinodular goiter, thyroiditis) 1
• Thyrotoxicosis with unclear etiology: To differentiate destructive thyroiditis from Graves' disease in patients on immune checkpoint inhibitors 1
• Pregnancy: TRAb ≥5 IU/L indicates increased risk of fetal/neonatal thyrotoxicosis requiring close monitoring 2

Supplementary Antibody Testing

Thyroid Peroxidase (TPO) Antibody

• Not diagnostic for Graves' disease but may be present in autoimmune thyroid conditions 1
• Useful for confirming autoimmune hypothyroidism (Hashimoto's thyroiditis) when TSH is elevated and free T4 is low 1
• Does not distinguish between Graves' disease and other autoimmune thyroid disorders 1

Clinical Algorithm for Antibody Testing

Step 1: Initial Thyroid Function Tests

• Measure TSH and free T4 (or free T3 if highly symptomatic with minimal FT4 elevation) 1
• Low TSH with elevated free T4/T3 indicates thyrotoxicosis 1

Step 2: Order TRAb When Thyrotoxicosis is Confirmed

• Order TSI or TBII to confirm Graves' disease as the etiology 1
• Consider adding TPO antibody if concurrent autoimmune thyroid disease is suspected 1

Step 3: Interpret Results

• Positive TRAb (TSI or TBII): Confirms Graves' disease diagnosis 1
• Negative TRAb: Consider alternative diagnoses (thyroiditis, toxic nodular disease, exogenous thyroid hormone) 1
• All 277 untreated Graves' patients in one study had positive TRAb (TSAb and/or TBII) 4

Important Caveats and Pitfalls

False Positives

• Mildly elevated TRAb can occur in transient thyroiditis: TSI elevated less than twice the upper limit of normal may be seen in self-limited thyrotoxicosis 5
• For clinically stable patients without pathognomonic Graves' features and mildly elevated TRAb, consider close monitoring or alternative testing (radioactive iodine uptake scan) before initiating definitive therapy 5

False Negatives

• Rare but possible; clinical diagnosis has 12% false negative rate compared to TRAb testing 6
• If clinical suspicion remains high despite negative TRAb, consider repeat testing or imaging studies 1

Biotin Interference

• High-dose biotin supplementation can interfere with some TRAb assays, leading to false results 5
• Discontinue biotin 2-3 days before testing if interference is suspected

Prognostic Value of TRAb

• TRAb >12 IU/L at diagnosis: 60% relapse risk at 2 years, 84% at 4 years 2
• TRAb >7.5 IU/L at 12 months of antithyroid drug therapy: >90% relapse risk 2
• TRAb >3.85 IU/L at cessation of therapy: >90% relapse risk 2
• Elevated TRAb levels favor definitive treatment (radioactive iodine or thyroidectomy) over continued medical management 2