What are the initial steps in the workup of hyperthyroidism?

Initial Workup of Hyperthyroidism

The initial workup of hyperthyroidism should begin with TSH and free T4 measurements, with T3 testing added for symptomatic patients with minimal FT4 elevations. 1, 2

Diagnostic Approach

Step 1: Laboratory Testing

• First-line tests:
  • TSH (thyroid-stimulating hormone)
  • Free T4 (thyroxine)
  • Consider Free T3 (triiodothyronine) in symptomatic patients with minimal FT4 elevations 2

Step 2: Determine Pattern of Abnormality

• Primary hyperthyroidism: Low TSH with elevated FT4 and/or FT3
• Subclinical hyperthyroidism: Low TSH with normal FT4 and FT3
• Central hyperthyroidism: Low TSH with low FT4 (evaluate for hypophysitis or other pituitary disorders) 2

Step 3: Etiological Diagnosis

After confirming biochemical hyperthyroidism, determine the underlying cause:

1. TSH receptor antibody testing if clinical features suggest Graves' disease (e.g., ophthalmopathy, T3 toxicosis) 2

2. Thyroid imaging:

   • Thyroid ultrasonography to evaluate for nodules, size, and vascularity
   • Thyroid scintigraphy (radioiodine uptake scan) if etiology remains unclear or nodules are present 1, 3

3. Additional laboratory tests based on clinical suspicion:

   • Thyroid peroxidase antibodies
   • Inflammatory markers (ESR, CRP) if thyroiditis suspected 1

Common Causes of Hyperthyroidism

Understanding the most likely causes helps guide the workup:

• Graves' disease (70% of cases) - diffuse toxic goiter with TSH receptor antibodies 1
• Toxic nodular goiter (16% of cases) - autonomous nodules 1
• Subacute thyroiditis (3% of cases) - inflammatory condition with transient hyperthyroidism 1
• Drug-induced (9% of cases) - amiodarone, tyrosine kinase inhibitors, immune checkpoint inhibitors 1

Special Considerations

Immune Checkpoint Inhibitor (ICPi) Therapy

For patients on ICPi therapy, thyroiditis is common and often self-limited:

• Monitor TSH and FT4 every 4-6 weeks as part of routine clinical monitoring
• The hyperthyroid phase typically resolves in weeks, often transitioning to hypothyroidism 2

Pregnancy

• Pregnancy can affect thyroid function tests
• TSH receptor antibody testing is particularly important in pregnant women with hyperthyroidism 3

Elderly Patients

• May present with atypical symptoms (apathy, weight loss, atrial fibrillation)
• Higher risk of cardiovascular complications 3

Common Pitfalls to Avoid

1. Relying solely on TSH: While the two-step approach (measuring TSH first, then FT4 only if TSH is abnormal) is efficient for screening, it may miss rare cases of central hyperthyroidism or thyroid hormone resistance 4

2. Overlooking protein binding anomalies: Conditions that affect thyroid hormone binding proteins can cause abnormal total T4 levels with normal free hormone levels 5

3. Misdiagnosing thyroiditis as Graves' disease: Transient hyperthyroidism due to thyroiditis requires different management than Graves' disease 1

4. Missing central hypothyroidism: Low TSH with low FT4 indicates central hypothyroidism, not hyperthyroidism, and requires evaluation for pituitary or hypothalamic disorders 2, 6

By following this systematic approach to the initial workup of hyperthyroidism, clinicians can efficiently diagnose the condition and determine its underlying cause, leading to appropriate treatment decisions that will improve patient outcomes.