What investigations are required to diagnose and manage hyperthyroidism?

Diagnostic Investigations for Hyperthyroidism

The essential investigations required to diagnose hyperthyroidism include thyroid function tests (TSH, FT4, FT3), thyroid antibody tests, and imaging studies when indicated. 1

Initial Laboratory Investigations

Primary Thyroid Function Tests

• TSH measurement: First-line test for suspected hyperthyroidism

  • Suppressed TSH (<0.4 mIU/L) is the most sensitive indicator of hyperthyroidism 2
  • Highly sensitive TSH assays can distinguish between suppressed levels in hyperthyroidism and normal levels 2

• Free T4 (FT4): Second-line test when TSH is abnormal

  • Elevated in most cases of overt hyperthyroidism
  • More reliable than total T4 as it's not affected by binding protein changes 3

• Free T3 (FT3): Important complementary test

  • Critical for detecting T3 toxicosis (elevated T3 with normal T4)
  • T3 toxicosis occurs in approximately 16% of hyperthyroid cases 4
  • FT3 and TSH combination provides 97.57% sensitivity for hyperthyroidism diagnosis 4

Antibody Testing

• TSH receptor antibodies (TRAb): Essential for determining etiology

  • Differentiates Graves' disease (positive) from other causes of hyperthyroidism
  • Correlates well with disease activity 3

• Thyroid peroxidase antibodies (TPOAb): Helpful for identifying autoimmune etiology

  • May be present in Graves' disease and Hashimoto's thyroiditis 3

Imaging Studies

When to Perform Imaging

• Thyroid ultrasound: Indicated when:

  • Palpable thyroid nodules are present
  • Suspicious clinical features exist
  • Differentiating between causes of hyperthyroidism 5

• Thyroid scintigraphy (radioiodine uptake scan): Useful for:

  • Differentiating Graves' disease (diffuse uptake) from toxic nodular goiter (focal uptake)
  • Identifying destructive thyroiditis (low uptake) 1
  • Particularly valuable in unusual cases of hyperthyroidism 6

Special Diagnostic Considerations

Differential Diagnosis Testing

• For suspected thyroiditis: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)

  • Elevated in subacute granulomatous thyroiditis 1

• For suspected pituitary adenoma (TSHoma):

  • MRI of the pituitary gland
  • Measurement of alpha subunit of TSH
  • Thyroid hormone resistance testing 7

Pregnancy Considerations

• More frequent monitoring of thyroid function tests during pregnancy
• TSH, FT4, and TRAb are essential for management 8

Monitoring During Treatment

• Thyroid function tests: Monitor periodically during therapy

  • Rising TSH indicates need for lower maintenance dose of antithyroid medication 9, 8

• Complete blood count: Monitor for agranulocytosis with antithyroid drugs

  • Particularly important in first 6 months of therapy 9, 8

• Liver function tests: Especially with propylthiouracil

  • Monitor for hepatotoxicity (bilirubin, alkaline phosphatase, ALT/AST) 8

• Prothrombin time: Before surgical procedures in patients on antithyroid drugs

  • Methimazole and propylthiouracil may cause hypoprothrombinemia 9, 8

Monitoring Frequency Based on TSH Levels

TSH Level	Monitoring Frequency
0.1-0.45 mIU/L	Every 3 months
<0.1 mIU/L	Every 4-6 weeks

Common Pitfalls to Avoid

1. Relying solely on TSH: While sensitive, TSH alone may be misleading in:

   • Central hyperthyroidism (pituitary adenoma)
   • Recent treatment of hyperthyroidism (TSH may remain suppressed)
   • Non-thyroidal illness

2. Missing T3 toxicosis: Always measure FT3 in cases with suppressed TSH but normal FT4 4

3. Overlooking drug-induced hyperthyroidism: Screen for medications that can cause hyperthyroidism:

   • Amiodarone
   • Immune checkpoint inhibitors
   • Tyrosine kinase inhibitors 1

4. Inadequate follow-up: Regular monitoring is essential during treatment to:

   • Prevent undertreatment or overtreatment
   • Detect potential complications early 7

By following this comprehensive diagnostic approach, clinicians can accurately diagnose hyperthyroidism, determine its etiology, and monitor treatment effectiveness while minimizing complications.