What labs should be ordered to diagnose Graves' disease?

Laboratory Testing for Graves' Disease Diagnosis

Order TSH receptor antibodies (TRAb or TSI) along with TSH and free T4 to diagnose Graves' disease. 1

Essential Laboratory Tests

First-Line Testing

• TSH and Free T4 are the initial screening tests for suspected hyperthyroidism, with TSH typically suppressed (<0.1 mIU/L) and free T4 elevated in Graves' disease 1
• TSH receptor antibodies (TRAb) should be measured when clinical features suggest Graves' disease, such as ophthalmopathy or diffuse goiter 1
• Total T3 or Free T3 should be measured alongside TSH and free T4, as some patients present with T3 toxicosis (elevated T3 with normal T4) 1

Confirmatory Testing for Graves' Disease

• TSH-stimulating immunoglobulin (TSI) or TRAb are the most important diagnostic tests for confirming Graves' disease, as these antibodies stimulate the TSH receptor causing thyroid hyperplasia and unregulated hormone production 2, 3
• TSI levels correlate inversely with TSH suppression—the more suppressed the TSH, the higher the TSI level, making TSH a reliable indirect marker of TSI activity 4
• Positive TRAb/TSI distinguishes Graves' disease from other causes of hyperthyroidism like thyroiditis or toxic nodular goiter 2

Diagnostic Algorithm

When to Order TRAb/TSI

• Clinical features of Graves' disease including ophthalmopathy, diffuse goiter, or thyroid bruit warrant immediate TRAb testing 1
• Persistent hyperthyroidism >6 weeks requires TRAb workup to distinguish Graves' disease from transient thyroiditis 1
• Severe symptoms (Grade 3-4) including thyroid storm, severe tachycardia, or cardiac complications necessitate urgent TRAb measurement 1

Supporting Diagnostic Tests

• Thyroid ultrasonography shows diffuse enlargement with increased vascularity (increased Doppler flow) in Graves' disease 2, 3
• Radioactive iodine uptake and scan can distinguish Graves' disease (diffusely increased uptake) from destructive thyroiditis (low uptake) when TRAb results are equivocal 1
• Thyroglobulin levels may be elevated and serve as a marker of thyroid stimulation 5

Critical Diagnostic Pitfalls

Common Errors to Avoid

• Do not rely on TSH and free T4 alone—these confirm hyperthyroidism but don't establish the etiology as Graves' disease 1
• Never miss T3 toxicosis—some patients have isolated T3 elevation with normal T4, requiring T3 measurement for diagnosis 1
• Distinguish from thyroiditis—transient hyperthyroidism from thyroiditis resolves in weeks without treatment, while Graves' disease persists and requires definitive therapy 1

Special Clinical Scenarios

• Ophthalmopathy or thyroid bruit are pathognomonic for Graves' disease and should prompt immediate endocrine referral even before lab confirmation 1
• Atypical presentations including "apathetic thyrotoxicosis" in elderly patients may delay diagnosis—maintain high clinical suspicion 6
• Pregnancy considerations—Graves' disease in pregnant women requires monitoring for fetal thyroid dysfunction, as maternal TRAb can cross the placenta 1

Expected Laboratory Findings in Graves' Disease

Typical Pattern

• TSH <0.1 mIU/L (often undetectable) 3, 4
• Elevated free T4 (>1.74 ng/dL) and/or elevated T3 (>200 ng/dL) 6, 4
• Positive TRAb/TSI (>140% of baseline is typically diagnostic) 2, 4
• Suppressed TSH with positive TRAb confirms active Graves' disease requiring treatment 5, 4

Monitoring During Treatment

• TRAb levels predict remission—disappearance of TRAb indicates potential for sustained remission after antithyroid drug discontinuation 5
• Persistent TRAb positivity >5 years suggests smoldering-type Graves' disease requiring long-term treatment 5
• TSH remains suppressed even after thyroid hormone normalization due to persistent TRAb stimulation 4