What is the diagnostic workup for a patient suspected of having hyperthyroidism?

Diagnostic Workup for Hyperthyroidism

The diagnostic workup for suspected hyperthyroidism should begin with measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels, with additional testing for free triiodothyronine (FT3) in cases with low TSH but normal FT4. 1

Initial Laboratory Testing

• First-line tests:

  • TSH (most sensitive screening test)
  • Free T4 (FT4)
  • Free T3 (FT3) - particularly useful in patients with low TSH but normal FT4 2

• Interpretation of results:

  • Overt hyperthyroidism: Low/suppressed TSH with elevated FT4 and/or FT3
  • Subclinical hyperthyroidism: Low TSH with normal FT4 and FT3
  • Values for serum TSH below 0.1 mU/L are generally considered low 3

Etiological Diagnosis

Once hyperthyroidism is biochemically confirmed, determine the underlying cause:

• Additional laboratory tests:

  • TSH receptor antibodies (TRAb) - for suspected Graves' disease
  • Thyroid peroxidase antibodies (TPO) - may be positive in autoimmune thyroid disorders
  • Thyroglobulin antibodies - may be present in autoimmune thyroid disease 1, 4

• Imaging studies:

  • Thyroid ultrasonography - evaluates gland size, nodules, vascularity
  • Radioactive iodine uptake scan (RAIUS) - differentiates Graves' disease (diffuse uptake) from toxic nodular goiter (focal uptake) or thyroiditis (low uptake)
  • Technetium-99m scan - alternative when recent iodinated contrast was used 3, 4

Common Causes to Consider

• Graves' disease (70% of cases) - diffuse toxic goiter with potential ophthalmopathy
• Toxic nodular goiter (16%) - single or multiple hyperfunctioning nodules
• Subacute thyroiditis (3%) - transient hyperthyroidism followed by hypothyroidism
• Drug-induced hyperthyroidism (9%) - amiodarone, tyrosine kinase inhibitors, immune checkpoint inhibitors 2

Special Considerations

• Thyroid storm - medical emergency requiring immediate hospitalization

  • Presents with extreme tachycardia, hyperthermia, altered mental status
  • Requires aggressive treatment with high-dose antithyroid drugs, beta-blockers, corticosteroids 1

• Pregnancy

  • TSH may be physiologically suppressed in first trimester
  • Requires careful monitoring as untreated hyperthyroidism increases risk of maternal heart failure, spontaneous abortion, preterm birth 1

• Elderly patients

  • May present with "apathetic hyperthyroidism" - minimal symptoms except for cardiovascular manifestations
  • More likely to have atrial fibrillation as presenting feature 1, 5

• Immune checkpoint inhibitor therapy

  • Monitor thyroid function every 4-6 weeks during treatment
  • Thyroiditis is common and often self-limited, progressing from hyperthyroidism to hypothyroidism 3

Clinical Evaluation

• Cardiovascular assessment:

  • Heart rate, rhythm, blood pressure
  • Signs of heart failure or atrial fibrillation 1

• Neurological assessment:

  • Tremor, hyperreflexia, anxiety
  • Muscle weakness, especially proximal 1

• Ophthalmologic examination:

  • Lid lag, lid retraction
  • Exophthalmos (proptosis)
  • Extraocular muscle dysfunction 1

• Dermatologic assessment:

  • Warm, moist skin
  • Pretibial myxedema (in Graves' disease)
  • Hair loss 1

Diagnostic Algorithm

1. Initial screening: TSH, FT4
2. If TSH is low:
   • Measure FT3 if FT4 is normal
   • Proceed with antibody testing (TRAb, TPO)
3. Imaging:
   • Thyroid ultrasound for all patients
   • Radioactive iodine uptake scan or technetium scan to determine etiology
4. Additional testing based on clinical suspicion:
   • Complete blood count (may show mild anemia)
   • Liver function tests (may be abnormal in severe hyperthyroidism)
   • Calcium levels (risk of hypercalcemia)

Common Pitfalls to Avoid

• Don't rely solely on clinical presentation - symptoms can be nonspecific or atypical, especially in elderly patients 5
• Don't miss subclinical hyperthyroidism - can still cause significant cardiovascular and bone complications 1
• Don't forget to check for drug-induced causes - review medication list thoroughly 2
• Don't misinterpret transient thyroiditis - can mimic Graves' disease but requires different management 3
• Don't overlook central hyperthyroidism - low TSH with low FT4 suggests central hypothyroidism, not hyperthyroidism 3

By following this systematic approach to diagnosing hyperthyroidism, clinicians can accurately identify the condition and its underlying cause, leading to appropriate treatment decisions and improved patient outcomes.