Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysis

Pediatrics. 2003 Feb;111(2):E132-9. doi: 10.1542/peds.111.2.e132.


Objectives: The aim of this study was first to investigate whether early total thyroidectomy (ETT; 1-5 years of age) can prevent medullary thyroid carcinoma with persistent or recurrent disease (PRD) in pediatric patients with multiple endocrine neoplasia type 2A (MEN-2A) and second, to evaluate the strength of codon analysis in children with MEN-2A as prognostic parameter.

Methods: Case reports and review of the literature for pediatric patients with MEN-2A were conducted. Inclusion criteria were age (0-20 years) and histologic degree of C-cell disease (normal = N, C-cell hyperplasia = CCH, medullary thyroid carcinoma = MTC, metastatic MTC = MMTC). To evaluate therapeutic results of ETT (1-5 years) versus late total thyroidectomy (LTT; 6-20 years), age-dependent histologic stages of C-cell disease and postoperative occurrence of PRD were compared. Prognostic value of specific codons, age-dependent histologic distribution, and long-term outcome were analyzed.

Results: In a total of 260 cases, 42 (16%) underwent ETT, and 218 (84%) underwent LTT. Histologic analysis showed significant difference between ETT versus LTT (57% vs 76%) regarding malignant stage of C-cell disease (of combined rate of MTC and MMTC). Long-term outcome was documented in 74 patients (28%). During a median follow-up period of 2 years (range: 0-15 years), 21 of 65 of the LTT group versus 0 of 9 of the ETT group suffered PRD. Information about codon analysis was available in 150 patients (58%). Mutated codons were c634 (63%), c618 (19%), c620 (9%), and c804 (6%). Codon-related histologic analysis resulted in prognostic differences: 81% of patients with c634-mutation had MCT or MMTC in contrast to c804 (44%), c618 (34%), and c620 (7%). Fifteen of 17 MMTC and 7 of 9 PRD occurred in patients with c634-mutation.

Conclusions: 1) ETT until 5 years of age in MEN-2A gene carriers results in significant reduction of MTC and MMTC in favor of CCH and improved disease-free long-term outcome. 2) Codon analysis is an important prognostic factor. Timing of TT could be individualized based on codon-specific prognosis. Until more detailed knowledge is available, consequent genetic and biochemical screening is mandatory for appropriate individual timing of ETT before age of 5 years.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Carcinoma, Medullary / prevention & control
  • Carcinoma, Medullary / secondary
  • Child
  • Child, Preschool
  • Codon / genetics*
  • Drosophila Proteins*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Hyperparathyroidism / epidemiology
  • Hyperparathyroidism / genetics
  • Infant
  • Multiple Endocrine Neoplasia Type 2a / diagnosis*
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Multiple Endocrine Neoplasia Type 2a / surgery*
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Neoplasms, Ductal, Lobular, and Medullary / genetics
  • Neoplasms, Ductal, Lobular, and Medullary / pathology
  • Neoplasms, Ductal, Lobular, and Medullary / prevention & control
  • Pheochromocytoma / epidemiology
  • Pheochromocytoma / genetics
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery*
  • Thyroidectomy / methods*
  • Treatment Outcome


  • Codon
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila