At what calcitonin (calcitonin) level should surgery be considered for a child under 5, specifically a girl with a known RET (ret proto-oncogene) mutation?

Timing of Thyroidectomy in Girls Under 5 with RET Mutations Based on Calcitonin Values

For girls under 5 years with RET mutations, prophylactic total thyroidectomy should be performed by age 5 regardless of calcitonin levels, with immediate intervention indicated if calcitonin becomes elevated or abnormal on stimulation testing. 1

Decision Algorithm Based on RET Mutation Risk Level

Highest Risk Mutations (Level D)

• RET codons 883,918,922 (MEN 2B)
• Action: Total thyroidectomy during the first year of life or at diagnosis
• Rationale: Highest risk of aggressive MTC development 1, 2

High Risk Mutations (Level B)

• RET codons 609,611,618,620,630,634 (MEN 2A)
• Action: Total thyroidectomy by age 5 years regardless of calcitonin level
• Rationale: Earliest reported MTC at age 7 for codon 618 mutations 1, 2

Moderate Risk Mutations (Level A)

• RET codons 768,790,791,804,891
• Action: Annual calcitonin testing and ultrasound; thyroidectomy may be deferred if tests normal
• Rationale: Lower lethality and later onset of MTC 1, 2

Calcitonin-Based Decision Making

1. Normal Calcitonin + High-Risk Mutation:

   • Proceed with prophylactic thyroidectomy by age 5
   • Don't wait for calcitonin elevation 1, 2

2. Elevated Basal Calcitonin (>50 pg/mL):

   • Immediate thyroidectomy regardless of age
   • Higher risk of advanced disease and lower surgical cure rate (34.3%) 3

3. Positive Stimulation Test (Normal Basal, Elevated Stimulated):

   • Immediate thyroidectomy
   • Better surgical cure rate (60%) compared to waiting for basal elevation 3

Surgical Approach Based on Disease Status

1. Prophylactic Surgery (No Evidence of Disease):

   • Total thyroidectomy alone
   • Consider bilateral central neck dissection (level VI) for MEN 2B 1

2. With Elevated Calcitonin or Abnormal Ultrasound:

   • Total thyroidectomy
   • Therapeutic ipsilateral or bilateral central neck dissection (level VI) 1

3. With Tumors >0.5 cm (MEN 2B) or >1.0 cm (MEN 2A):

   • Total thyroidectomy
   • More extensive lymph node dissection (levels II-V) 1

Importance of Early Intervention

The surgical cure rate differs dramatically based on timing:

• 89% cure rate for early detection ("converters")
• Only 25% cure rate for symptomatic MTC patients 1, 2

Monitoring Protocol

For girls awaiting surgery or with moderate-risk mutations:

• Annual calcitonin measurement starting at age 3
• Annual thyroid ultrasound
• Screening for pheochromocytoma and hyperparathyroidism starting at age 10 (every 2 years) 1, 2

Important Caveats

1. Surgeon Selection: Refer to a surgeon and team experienced in pediatric thyroid surgery due to higher risks of complications in very young children 1

2. Preoperative Screening: Always screen for pheochromocytoma before thyroid surgery to prevent hypertensive crisis 1, 2

3. False Negatives: Rare cases of MTC without calcitonin elevation exist, so genetic status should guide decision-making more than calcitonin levels 4

4. Postoperative Management: Normalize (not suppress) TSH with levothyroxine; C-cells lack TSH receptors 1

5. Variable Penetrance: Some mutations show variable penetrance, but prophylactic surgery is still recommended for high-risk mutations due to potential aggressive behavior 5, 6

The evidence strongly supports early prophylactic thyroidectomy by age 5 for girls with high-risk RET mutations, regardless of calcitonin levels, to maximize survival and quality of life outcomes.