What are the symptoms and screening methods for Medullary Thyroid Cancer (MTC)?

Symptoms and Screening for Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) requires screening with serum calcitonin measurement, genetic testing for RET mutations, and fine-needle aspiration of suspicious thyroid nodules for early detection and optimal management.

Clinical Presentation and Symptoms

• More than 50% of malignant thyroid nodules, including MTC, are asymptomatic at presentation 1

• When symptomatic, MTC may present with:

  • Thyroid nodule(s), typically in the upper portion of thyroid lobes (where C cells are predominantly located) 1
  • Cervical lymphadenopathy (present in approximately 50% of patients at initial diagnosis) 1
  • Upper aerodigestive tract compression or invasion symptoms (in up to 15% of patients) 1
  • Diarrhea, Cushing's syndrome, or facial flushing (due to secretion of calcitonin and other hormones like ACTH or calcitonin-gene related peptide) 1
  • Symptoms from distant metastases in lungs or bones (in 5-10% of patients) 1

• Physical examination findings that increase suspicion for MTC include:

  • Very firm nodules
  • Nodules fixed to adjacent structures
  • Rapidly growing nodules
  • Enlarged regional lymph nodes
  • Vocal cord paralysis 1

Screening Approaches

Initial Evaluation of Suspicious Thyroid Nodules

• Fine-needle aspiration (FNA) is the preferred procedure for evaluating suspicious thyroid nodules 1
• Ultrasound of the thyroid and central neck should be performed 1
• Suspicious ultrasound criteria include:
  • Central hypervascularity
  • Microcalcifications
  • Irregular borders 1

Biochemical Screening

• Serum calcitonin measurement is essential when MTC is suspected 1, 2

  • Elevated calcitonin is a highly sensitive and specific tumor marker for MTC 3
  • Calcitonin levels correlate with tumor burden 3
  • Levels >150 pg/mL warrant screening for distant metastases 1
  • Levels >400 pg/mL indicate need for additional imaging studies 1, 2

• Carcinoembryonic antigen (CEA) should be measured as an additional tumor marker 1, 2

Genetic Testing

• All patients with confirmed MTC should undergo DNA analysis for RET proto-oncogene mutations 1, 2
• Genetic testing helps distinguish between:
  • Sporadic MTC (75% of cases)
  • Hereditary MTC (25% of cases) as part of Multiple Endocrine Neoplasia (MEN) type 2 syndromes 1, 4

Additional Workup for Confirmed or Suspected MTC

• If MTC is diagnosed or suspected:
  • Measure serum calcium to screen for hyperparathyroidism 1
  • Screen for pheochromocytoma with plasma metanephrines and normetanephrines or 24-hour urine collection for metanephrines 1
  • Consider neck CT with contrast or MRI if lymph node involvement is present 1
  • For calcitonin levels >400 pg/mL, consider additional imaging:
    • Chest CT with contrast
    • Three-phase contrast-enhanced liver CT or MRI 1

Special Considerations

• Risk factors that increase suspicion for MTC include:

  • Age <15 years
  • Male gender
  • Family history of thyroid cancer
  • History of diseases associated with MTC (MEN2A, MEN2B) 1

• Hereditary MTC screening should include:

  • RET mutation testing of first-degree relatives 1
  • Prophylactic thyroidectomy timing based on specific RET mutation and calcitonin level 3

• Common pitfalls in MTC diagnosis:

  • Relying solely on FNA without calcitonin measurement (may miss MTC) 2, 5
  • Failure to perform genetic testing in all MTC patients 4
  • Inadequate screening for associated endocrinopathies in hereditary forms 1