What is the optimum management of medullary thyroid carcinoma 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 bilateral central neck dissection (level VI), with consideration for more extensive lymph node dissection based on tumor size and nodal status.

Surgical Management Algorithm

Preoperative Considerations

1. Screen for pheochromocytoma first

   • Must be identified and treated before thyroid surgery to prevent potentially fatal hypertensive crisis 1, 2
   • Preoperative preparation includes α-adrenergic blockade (phenoxybenzamine) or α-methyltyrosine
   • Surgical approach typically involves laparoscopic adrenalectomy

2. Evaluate for hyperparathyroidism (in MEN 2A)

   • Measure serum intact parathyroid hormone and calcium 1

Surgical Approach Based on Disease Status

For Prophylactic Surgery (Based on RET Mutation Risk Level)

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

  • Total thyroidectomy during the first year of life or at diagnosis 1, 2
  • Consider bilateral central neck dissection (level VI)

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

  • Total thyroidectomy by age 5 years or when mutation identified 1, 2
  • Therapeutic ipsilateral or bilateral central neck dissection if elevated calcitonin/CEA or abnormal ultrasound

• Moderate Risk (Level A - codons 768,790,791,804,891)

  • Annual basal calcitonin testing and ultrasound
  • Total thyroidectomy may be deferred if tests are normal, no aggressive family history, and family agrees 1

For Established MTC

• For tumors ≥1 cm or bilateral disease

  • Total thyroidectomy and bilateral central neck dissection (level VI) 1
  • Consider more extensive lymph node dissection (levels II-V) for tumors >1.0 cm or if central nodes positive

• For tumors <1 cm with unilateral disease

  • Total thyroidectomy (neck dissection can be considered) 1

Postoperative Management

1. Thyroid Hormone Replacement

   • Postoperative levothyroxine to normalize TSH (not suppress) 1
   • C cells lack TSH receptors, so TSH suppression is not appropriate

2. Surveillance (2-3 months postoperative)

   • Serum calcitonin and CEA monitoring
   • If calcitonin is detectable or CEA elevated:
     • Neck imaging
     • Consider additional imaging if calcitonin >150 pg/mL
     • Contrast-enhanced CT or MRI of neck, chest, abdomen with liver protocol

3. Long-term Follow-up

   • Annual screening for pheochromocytoma and hyperparathyroidism (MEN 2A) 1, 2
   • Regular calcitonin and CEA monitoring

Important Considerations and Pitfalls

• Radioactive iodine is ineffective for MTC as C cells do not concentrate iodine 1
• Thyroid lobectomy alone is inadequate due to the high risk of bilateral disease and lymph node metastases 1, 3
• Referral to experienced surgeons is crucial, especially for pediatric cases, to minimize complications like hypoparathyroidism and recurrent laryngeal nerve injury 1, 2
• Surgical cure rates are significantly higher in presymptomatic carriers (89%) compared to symptomatic patients (25%) 2
• MEN 2B has more aggressive disease than MEN 2A, with earlier onset and higher rates of nodal metastases 4

The evidence clearly demonstrates that total thyroidectomy with appropriate lymph node dissection offers the best chance for cure and improved survival in patients with MEN 2-related MTC. Radioactive iodine and thyroid lobectomy alone are inadequate treatment options, and radiotherapy is generally reserved for cases with gross unresectable disease or symptomatic metastases.