What are the initial lab evaluations for a thyroid nodule?

Initial Laboratory Evaluation for Thyroid Nodules

The initial laboratory evaluation for a thyroid nodule should include measurement of serum thyroid-stimulating hormone (TSH) and serum calcitonin. 1

Core Laboratory Tests

Thyroid Function Tests

• Serum TSH: This is the best initial laboratory test for thyroid function 1
  • If TSH is low or suppressed: Follow with measurement of free thyroxine and consider a thyroid scan with 99Tc to determine if the nodule is "hot" (functioning) or "cold" (non-functioning) 1
  • If TSH is high: Measure thyroid peroxidase antibodies to evaluate for autoimmune thyroid disease 1

Calcitonin Measurement

• Serum calcitonin: Should be an integral part of the diagnostic evaluation of thyroid nodules 1
  • Higher sensitivity than FNAC for detecting medullary thyroid cancer (MTC), which represents 5-7% of all thyroid cancers 1
  • Particularly important as early detection of MTC can significantly reduce mortality 1

Diagnostic Algorithm

1. First step: Measure serum TSH
2. Second step: Measure serum calcitonin
3. Third step: Based on TSH results:
   • Normal TSH: Proceed with ultrasound and FNAC evaluation
   • Low TSH: Perform thyroid scan and measure free thyroxine
   • High TSH: Measure thyroid peroxidase antibodies

Imaging and Cytological Evaluation

While not laboratory tests, these are critical components of the complete evaluation:

• Thyroid ultrasound: Should be performed in all patients with thyroid nodules 1

  • Evaluates nodule characteristics that suggest malignancy: hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow, and shape (taller than wide) 1

• Fine-needle aspiration cytology (FNAC): Should be performed for:

  • Any thyroid nodule >1 cm 1
  • Nodules <1 cm with suspicious clinical features (history of head and neck irradiation, family history of thyroid cancer, suspicious features on palpation, presence of cervical adenopathy) or suspicious ultrasound features 1

Important Considerations

• Thyroglobulin (Tg) measurement is of little help in the initial diagnosis of thyroid cancer and is not recommended as part of the initial evaluation 1
• Routine molecular testing (BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations) is not part of the initial laboratory evaluation but may be considered for indeterminate cytology results 1
• While some European centers routinely measure calcitonin in all patients with thyroid nodules, there has been controversy about cost-effectiveness in the United States 1

Common Pitfalls to Avoid

• Relying solely on thyroid function tests without proceeding to ultrasound and FNAC when indicated
• Omitting calcitonin measurement, which could miss cases of medullary thyroid carcinoma
• Ordering unnecessary tests like thyroglobulin in the initial evaluation
• Failing to obtain a thyroid scan when TSH is suppressed, which could miss autonomous functioning nodules

By following this structured approach to laboratory evaluation of thyroid nodules, clinicians can efficiently identify patients who require further investigation or treatment while minimizing unnecessary testing.