What is the optimum management of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2 (MEN 2)?

Optimal Management of Medullary Thyroid Carcinoma in MEN 2

The optimal management of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2 (MEN 2) is total thyroidectomy with appropriate neck dissection (option e), as this is the only potentially curative treatment approach for this condition. 1

Surgical Management Based on Risk Stratification

The surgical approach for MTC in MEN 2 should be guided by risk stratification based on specific RET mutations:

1. Highest Risk (Level D - MEN 2B, codons 883,918, or compound heterozygous mutations):

   • Total thyroidectomy during the first year of life or at diagnosis
   • Bilateral central neck dissection (level VI) is recommended
   • More extensive lymph node dissection may be needed as MTC can metastasize early 1, 2

2. High Risk (Level B - MEN 2A, codons 609,611,618,620,630,634):

   • Total thyroidectomy by age 5 years or when mutation is identified
   • Bilateral central neck dissection for tumors ≥1 cm 1

3. Moderate Risk (Level A):

   • Annual calcitonin testing and ultrasound monitoring
   • Total thyroidectomy when tests become abnormal 1

Extent of Surgery

For established MTC in MEN 2:

• Primary procedure: Total thyroidectomy (never lobectomy alone)
• Lymph node management:
  • Tumors ≥1 cm or bilateral disease: Total thyroidectomy with bilateral central neck dissection (level VI)
  • Tumors >1 cm or positive central nodes: Consider more extensive lymph node dissection (levels II-V)
  • Tumors <1 cm with unilateral disease: Total thyroidectomy with consideration for neck dissection 1, 3

Why Radioactive Iodine and Other Options Are Ineffective

• Radioactive iodine (option c): Ineffective for MTC as C cells do not concentrate iodine 1
• Thyroid lobectomy alone (option a): Inadequate due to high risk of bilateral disease and lymph node metastases 1
• Thyroid lobectomy with cervical lymphadenectomy (option b): Insufficient as total thyroidectomy is required
• Radiotherapy (option d): Not a primary treatment; may be considered for unresectable residual disease 1, 4

Preoperative Considerations

• Critical: Screen for pheochromocytoma before thyroid surgery to prevent potentially fatal hypertensive crisis
• Preoperative preparation includes α-adrenergic blockade if pheochromocytoma is present
• Evaluate for hyperparathyroidism in MEN 2A by measuring serum intact parathyroid hormone and calcium 1

Postoperative Management

• Postoperative levothyroxine to normalize TSH (not suppress)
• Surveillance 2-3 months postoperative with serum calcitonin and CEA monitoring
• Additional imaging if calcitonin is detectable or CEA elevated 1

Common Pitfalls to Avoid

1. Failure to screen for pheochromocytoma before thyroid surgery can lead to fatal hypertensive crisis
2. Delayed diagnosis in MEN 2B significantly impacts outcomes
3. Inadequate extent of thyroidectomy (lobectomy instead of total thyroidectomy)
4. Overlooking family screening and genetic testing
5. Inappropriate TSH suppression postoperatively 1

Evidence of Early MTC Development

Research has demonstrated that bilateral millimetric MTC may be present during the first year of life in MEN 2 patients, with lymph node metastases occurring early in MEN 2B patients. This supports the recommendation for early and complete surgical intervention 2.

The evidence clearly shows that complete surgical resection with total thyroidectomy and appropriate lymph node dissection is the only potential cure for MTC in MEN 2, and prophylactic surgery based on genetic testing has revolutionized management of this condition 1, 3.