What is the recorded age range for diagnosis of Medullary Thyroid Carcinoma (MTC) and typical calcitonin values in individuals with the RET (Receptor Tyrosine Kinase) 634F mutation?

Age Range and Calcitonin Values for RET 634F Mutation in MTC

For individuals with RET 634F mutation, medullary thyroid carcinoma (MTC) typically develops at a young age, with diagnosis commonly occurring between ages 5-35 years, and calcitonin values can range from normal levels to significantly elevated (>300 pg/mL) depending on disease progression.

Age Range for MTC Diagnosis with RET 634F Mutation

The RET 634F mutation is classified as a high-risk mutation (Grade 2) that requires early intervention:

• Earliest presentation: MTC can develop in early childhood, with cases documented as young as 5-7 years of age 1
• Mean age of C-cell stimulation test conversion: 23 years (range: 18-31 years) 1
• Disease penetrance: 100% of carriers will eventually develop MTC if left untreated 1
• Recommended prophylactic thyroidectomy: Before age 5-6 years 1, 2

Calcitonin Values in RET 634F Mutation Carriers

Calcitonin serves as the primary biomarker for MTC, with values varying by age and disease stage:

• Normal baseline in young children: Up to 50 pg/mL in infancy, with decreasing trend over the first three years of life 1, 2

• Early disease detection:

  • Case report of an 8-year-old with RET Cys634Gly mutation showed baseline calcitonin of 11.3 pg/mL that increased to 333 pg/mL with calcium stimulation 3
  • Stimulated calcitonin tests may detect disease before basal levels become elevated

• Post-thyroidectomy values:

  • Successful prophylactic surgery typically results in undetectable calcitonin levels 1, 2
  • Elevated post-operative calcitonin indicates at least stage III disease (T1-4N1M0) 1

Important Clinical Considerations

1. Surveillance protocol:

   • Annual calcitonin screening and thyroid ultrasound beginning at age 3 for RET 634F mutation carriers 2
   • Calcitonin is more sensitive than ultrasound for early MTC detection 2

2. Disease progression pattern:

   • Age-related progression from C-cell hyperplasia to MTC and eventually nodal metastasis 4
   • No lymph node metastases have been noted in patients younger than 14 years of age 4

3. Surgical outcomes:

   • Surgical cure rate for symptomatic MTC patients: 25%
   • Surgical cure rate for early detection ("converters"): 89% 1

4. Atypical presentations:

   • Rare cases of calcitonin-negative MTC have been reported, making diagnosis challenging 5, 6
   • These cases may still show positive immunohistochemical staining for calcitonin, CEA, or chromogranin A 6

Management Algorithm

1. For carriers identified before age 5:

   • Annual calcitonin screening and thyroid ultrasound beginning at age 3
   • Prophylactic total thyroidectomy by age 5 regardless of calcitonin levels

2. For carriers identified after age 5:

   • Immediate calcitonin testing and thyroid ultrasound
   • Total thyroidectomy with consideration for central neck dissection if:
     • Any elevation in calcitonin
     • Nodules identified on ultrasound
     • Age >5 years regardless of calcitonin levels

3. Post-thyroidectomy:

   • Serum calcitonin monitoring 2-3 months post-operation
   • Annual screening for pheochromocytoma and hyperparathyroidism (which occur in higher rates with codon 634 mutations) 2

The RET 634F mutation is associated with a high risk of MTC development at an early age, emphasizing the importance of early genetic testing, regular monitoring of calcitonin levels, and timely prophylactic thyroidectomy to prevent metastatic disease and improve survival outcomes.