What tests can distinguish Grave's disease from thyroiditis?

Testing to Distinguish Grave's Disease from Thyroiditis

To distinguish Grave's disease from thyroiditis, thyroid stimulating hormone receptor antibody (TRAb or TSI) testing and thyroid imaging with radioactive iodine uptake scan (RAIUS) or Technetium-99m scan are the most definitive diagnostic tests. 1

Initial Laboratory Testing

• TSH, Free T4, and Free T3: These are essential baseline tests for any thyrotoxicosis evaluation 1
• Free T3/Free T4 ratio: A ratio >4.4 (10^-2 pg/ng) suggests Graves' disease (sensitivity 47.2%, specificity 92.8%) 2
• T3/T4 ratio: Higher ratios are typically seen in Graves' disease compared to thyroiditis 3

Definitive Testing

Antibody Testing

• TSH receptor antibody (TRAb) or thyroid stimulating immunoglobulin (TSI):
  • Positive in Graves' disease (typically ≥15%)
  • Usually negative in thyroiditis (though can be positive in up to 10% of thyroiditis cases) 1, 4
  • Should be considered when clinical features suggest Graves' disease 1

Imaging Studies

• Radioactive iodine uptake scan (RAIUS):

  • High uptake in Graves' disease
  • Low uptake in thyroiditis 1, 5
  • Considered the reference standard for differentiation 5

• Technetium-99m pertechnetate thyroid scan:

  • Alternative to RAIUS if recent iodinated contrast was used
  • Shows increased uptake in Graves' disease and decreased uptake in thyroiditis 1, 3

• Thyroid ultrasound with Doppler flow:

  • Increased thyroid blood flow (>4%) in Graves' disease
  • Normal to low thyroid blood flow (<4%) in thyroiditis 4
  • Mean peak systolic velocity in inferior thyroid artery (mean PSV-ITA) shows sensitivity of 85.2% and specificity of 90.9% for Graves' disease 3

• Diffusion-weighted MRI imaging (DWI):

  • Higher apparent diffusion coefficient (ADC) values in Graves' disease compared to thyroiditis
  • Sensitivity 96.1%, specificity 91.9% 5

Clinical Features That Help Differentiate

• Physical examination findings:

  • Ophthalmopathy (eye involvement) is diagnostic of Graves' disease 1
  • Thyroid bruit is diagnostic of Graves' disease 1

• Disease course:

  • Thyroiditis is typically self-limiting, resolving in weeks with supportive care 1
  • Graves' disease is generally persistent without specific treatment 1

Diagnostic Algorithm

1. Obtain TSH, Free T4, Free T3 levels
2. Calculate Free T3/Free T4 ratio
3. If clinical features suggest Graves' disease (ophthalmopathy, thyroid bruit), proceed directly to TRAb testing
4. If TRAb is positive and clinical features are consistent, diagnosis is Graves' disease
5. If TRAb is negative or indeterminate, proceed to imaging:
   • RAIUS or Technetium-99m scan (preferred)
   • Thyroid ultrasound with Doppler flow (if nuclear medicine unavailable)
6. Monitor disease course - persistent thyrotoxicosis >6 weeks suggests Graves' disease 1

Common Pitfalls

• Relying solely on antibody testing may miss some cases of Graves' disease or lead to false positives in thyroiditis 1
• Failing to recognize that thyroiditis typically resolves spontaneously within weeks, while Graves' disease persists 1
• Not considering that recent iodine exposure can invalidate RAIUS results 1
• Missing the diagnosis of central hypothyroidism (low TSH with low Free T4) which requires evaluation for hypophysitis 1
• Not recognizing that some patients with thyroiditis may initially present with thyrotoxicosis but later develop hypothyroidism 1

When diagnostic uncertainty persists despite initial testing, endocrinology consultation is recommended for further evaluation and management 1.