Review of Multiple Endocrine Neoplasia Type 2A in Children: Therapeutic Results of Early Thyroidectomy and Prognostic Value of Codon Analysis

Abstract

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.