From the Guidelines
For a definitive diagnosis of Graves' disease, I strongly recommend ordering thyroid function tests including TSH, free T4, and free T3, as well as TSH receptor antibody testing, as these are crucial for confirming the autoimmune nature of the condition and guiding treatment decisions. When evaluating a patient for Graves' disease, it is essential to consider the clinical presentation and suspicion of the disease, as noted in the 2021 study published in the Journal of Clinical Oncology 1. The initial workup should include:
- TSH and free T4 (FT4) for case detection in symptomatic patients
- T3 can be helpful in highly symptomatic patients with minimal FT4 elevations
- TSH receptor antibody testing if there are clinical features and suspicion of Graves’ disease, such as ophthalmopathy and T3 toxicosis Additionally, the 2019 study published in the Journal of the American College of Radiology 1 highlights the importance of measuring TSH receptor antibodies for diagnosing Graves disease. While the 2004 study published in JAMA 1 provides guidance on evaluating subclinical thyroid disease, the more recent studies 1 provide more relevant and up-to-date recommendations for diagnosing Graves' disease. Therefore, thyroid function tests and TSH receptor antibody testing are the cornerstone of diagnosing Graves' disease, and should be prioritized in the initial workup.
From the Research
Laboratory Tests for Graves' Disease Diagnosis
The following laboratory tests are recommended for the diagnosis of Graves' disease:
- Measurement of TSH-R-Ab for an accurate diagnosis/differential diagnosis 2
- Thyroid-stimulating hormone (TSH) assay as the first-line biological assessment in case of clinically suspected thyrotoxicosis 3
- Free T4 and possibly free T3 assays to assess biological severity and monitor treatment efficacy 3
- Thyrotropin-binding inhibitory immunoglobulin (TBII) assay or thyroid-stimulating immunoglobulin (TSI) bioassay to differentiate Graves' disease from other causes of thyrotoxicosis 4
- Thyroid ultrasound scan, which may be contributive but is not recommended in first line 3
- Scintigraphy, reserved for rare cases of Graves' disease with negative antibody findings or when another etiology is suspected 3
Additional Considerations
- The presence of stimulatory autoantibodies (Ab) in GD activates the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion 2
- A hypervascular and hypoechoic thyroid gland on ultrasound, and associated orbitopathy, can support the diagnosis of Graves' disease 2
- The diagnostic accuracy of thyroid-stimulating hormone-binding inhibitory immunoglobulin assays has been improved, but a minority of patients with Graves' disease may test negative even on second-generation and third-generation assays 5
- Serum TSH level may be more reflective of the circulating TSI concentration than is thyroid gland function as expressed by free T4 and T3 concentrations 6