Initial Laboratory Tests for Diagnosing Graves' Disease
The initial laboratory workup for suspected Graves' disease should include TSH and free T4, followed by TSH receptor antibodies (TRAb or TSI) for confirmation when the diagnosis is not clinically obvious. 1, 2
First-Line Testing
TSH and Free Thyroid Hormones
- TSH is the recommended initial screening test for any patient with suspected thyroid dysfunction 1
- TSH and free T4 (FT4) should be measured together in patients with suspected hyperthyroidism 1
- T3 measurement is helpful in highly symptomatic patients with minimal FT4 elevations or when T3 toxicosis is suspected 1
- The classic pattern in Graves' disease shows suppressed TSH with elevated free T4 and/or T3 1
TSH Receptor Antibodies
- TSH receptor antibody testing (TRAb or TSI) is the most important confirmatory test for Graves' disease 1, 3
- First-line anti-TSH receptor antibody screening is recommended when clinical presentation is not unambiguous, due to excellent sensitivity and specificity 2
- TSI demonstrates superior diagnostic performance with sensitivity of 98.8% and specificity of 96.4% at a clinical cut-off of 0.467 IU/L 4
- TRAb shows sensitivity of 96.6% and specificity of 97.1% at a clinical cut-off of 1.245 IU/L 4
- Positive TSH receptor antibodies confirm the autoimmune etiology and distinguish Graves' disease from other causes of thyrotoxicosis 1, 3
When Additional Testing May Be Omitted
- If clinical presentation is unambiguous with clear extra-thyroid signs (such as ophthalmopathy or thyroid bruit), complementary etiological examinations may not be required after biochemical confirmation of thyrotoxicosis 1, 2
- Physical examination findings of ophthalmopathy or thyroid bruit are diagnostic of Graves' disease and should prompt early endocrine referral 1
Additional Considerations
Thyroid Peroxidase Antibodies
- Thyroid peroxidase (TPO) antibody testing can be performed as additional thyroid antibody assessment when hypothyroidism is confirmed 1
- TPO antibodies help identify autoimmune thyroid disease but are less specific for Graves' disease than TSH receptor antibodies 1
Clinical Pitfalls
- Normal TSH does not rule out thyrotoxicosis in the setting of central hypothyroidism; low TSH with low FT4 suggests pituitary dysfunction rather than Graves' disease 1
- Serum TSH may be more reflective of circulating TSI concentration than thyroid function itself, showing significant negative correlation (r = -0.45) with TSI levels 5
- Free T4 and T3 levels can show considerable variability and may not correlate as reliably with disease activity as TSH suppression 5