What are the guidelines for monitoring calcitonin levels and performing thyroid ultrasound in a 1-year-old child with RET (Ret proto-oncogene) 634F mutation to screen for medullary thyroid carcinoma (MTC)?

Monitoring Guidelines for a 1-Year-Old Child with RET634F Mutation

For a 1-year-old child with RET634F mutation, annual calcitonin screening and thyroid ultrasound should begin at 3 years of age, with thyroidectomy recommended by age 5 or when calcitonin levels become elevated. 1

Risk Classification and Monitoring Approach

The RET634F mutation is classified as a "high-risk" mutation (codon 634) that requires structured surveillance and timely intervention:

Initial Assessment (Current Age: 1 Year)

• No immediate calcitonin testing or ultrasound is recommended at this age
• Document family history of MTC aggressiveness
• Genetic counseling for family members

Monitoring Schedule

1. Begin annual screening at age 3 years 1, 2:

   • Annual serum calcitonin measurement
   • Annual thyroid ultrasound
   • Continue until thyroidectomy is performed

2. Proceed to thyroidectomy when either:

   • Calcitonin levels show an upward trend or become elevated
   • Ultrasound identifies thyroid abnormalities
   • Child reaches 5 years of age (even with normal tests) 1, 2

Important Considerations for Calcitonin Testing

• Physiological considerations: Calcitonin levels in infancy may be as high as 50 pg/mL with a decreasing trend over the first three years of life, limiting the utility of this marker in very young children 1
• Interpretation challenges: Age-dependent reference ranges should be used for children 3
• Testing method: Electro chemiluminescence immuno-assay (ECLIA) has been shown to be effective for early MTC detection in children with high-risk RET mutations 4
• Stimulation testing: Calcium stimulation testing may be considered in cases where basal calcitonin results are equivocal 5

Ultrasound Considerations

• Ultrasound appears to be less sensitive than calcitonin for diagnosis of MTC and should not be used alone to exclude malignancy or delay surgery 1
• Ultrasound serves multiple purposes:
  • Document normal gland in at-risk individuals
  • Pre-operative staging when surgery is planned
  • Detection of cervical adenopathy

Additional Monitoring

• Pheochromocytoma screening: Should be performed annually, as codon 634 variants are associated with higher risks of pheochromocytoma 1, 2
• Hyperparathyroidism screening: Serum calcium and PTH monitoring should be performed annually, as codon 634 variants are associated with higher risks of hyperparathyroidism 1, 2

Surgical Planning

When thyroidectomy becomes indicated:

• Refer to a surgeon experienced in pediatric thyroid surgery 1
• Preoperative staging with ultrasound is essential to identify regional lymphadenopathy 1
• Total thyroidectomy by age 5 years is recommended for high-risk mutations like codon 634 1, 2

Common Pitfalls to Avoid

• Delaying surveillance: Starting monitoring too late can miss early disease
• Over-reliance on ultrasound: Remember that calcitonin is more sensitive for early detection
• Ignoring family history: The aggressiveness of MTC in other family members with the same mutation should inform management decisions
• Failure to screen for associated conditions: Pheochromocytoma must be ruled out before any thyroid surgery 2

By following these guidelines, early detection of medullary thyroid carcinoma can be achieved, allowing for timely intervention and improved outcomes for children with RET634F mutations.