What labs to order with Fine Needle Aspiration (FNA) for a Thyroid Imaging, Reporting and Data System (TI-RADS) 5 nodule?

Laboratory Tests to Order with Fine Needle Aspiration for TI-RADS 5 Thyroid Nodules

For TI-RADS 5 thyroid nodules, serum TSH (thyroid-stimulating hormone) should be ordered with fine needle aspiration (FNA) as the primary laboratory test. 1, 2

Primary Laboratory Tests

1. Thyroid-Stimulating Hormone (TSH)
   • Should ideally be known before FNA is performed, though it may be impractical to wait for results before proceeding with FNA during the initial visit 1
   • Higher TSH levels are associated with increased risk for differentiated thyroid cancer 1
   • Helps determine thyroid functional status which impacts management decisions

Additional Tests to Consider Based on Clinical Context

For Suspected Medullary Thyroid Carcinoma (MTC)

• Serum Calcitonin
  • Not routinely recommended for all thyroid nodules in the US 1
  • Consider if there are clinical features suggesting MTC:
    • Family history of MTC or Multiple Endocrine Neoplasia (MEN) syndromes
    • History of hyperparathyroidism, pheochromocytoma
    • Presence of mucosal neuromas or marfanoid habitus 1

For FNA Specimens

• Immunohistochemical Studies
  • Calcitonin staining if MTC is suspected 1
  • Helps differentiate between various thyroid malignancies when cytology is inconclusive

Clinical Considerations for TI-RADS 5 Nodules

TI-RADS 5 nodules have >50% risk of malignancy and demonstrate highly suspicious features such as:

• Microcalcifications
• Irregular margins
• Hypervascularity 2

Important Pitfalls to Avoid

1. Do not delay FNA due to pending TSH results if it would significantly postpone diagnosis 1
2. Do not rely solely on reassuring FNA results when clinical findings are worrisome 1
3. Do not routinely measure calcitonin in all patients with thyroid nodules, as this practice remains controversial in the US due to:
   • Cost-effectiveness concerns
   • Lack of confirmatory pentagastrin stimulation testing (unavailable in the US)
   • Risk of unnecessary thyroidectomy in patients with false-positive results 1

Special Considerations

• Pathology and cytopathology slides should be reviewed by a pathologist with expertise in thyroid disorders 1
• Some malignancies can mimic others cytologically:
  • Hürthle cell neoplasms can mimic medullary carcinoma
  • Metastatic renal carcinoma can mimic follicular neoplasm
  • Melanoma can mimic medullary carcinoma
  • Metastatic lung cancer can mimic anaplastic carcinoma 1

By focusing on TSH measurement with FNA for TI-RADS 5 nodules, clinicians can efficiently evaluate these high-risk thyroid nodules while avoiding unnecessary testing that does not impact management decisions related to morbidity, mortality, and quality of life outcomes.