The clinical diagnosis, treatment and RET proto-oncogene screening in three multiple endocrine neoplasia type 2A pedigrees

Abstract

Objective To discuss clinical characteristics,treatment and clinical significance for RET screening in 3 multiple endocrine neoplasia type 2A (MEN2A) pedigrees.Methods The clinical data of 10 MEN2A patients from 3 unrelated MEN2A pedigrees from April 1990 to December 2011 were analyzed.There were 4 males and 6 females.5 patients with symptomatic palpable neck masses underwent bilateral total thyroidectomy + bilateral neck lymph node dissection.Other 5 RET screening detected asymptomatic thyroid cancer patients underwent bilateral total thyroidectomy + bilateral level Ⅵ lymph node dissection.6 adrenal pheochromocytoma (PHEO) patients received bilateral adrenalectomy (5 cases) or unilateral adrenalectomy (1 case).23 members from 3 families agreed to participate in biochemical testing,image examinations and RET screening.Results Histopathology revealed bilateral medullary thyroid carcinoma (MTC) in all 10 patients (100％).The two groups (symptomatic and asymptomatic) have significantly differences from the first diagnostic age [39.0 (31-64) years vs.18.2 (5.5-36) years],tumor maximum diameter [2.8 (1.2-5.6) cm vs.0.7 (0.2-1.3) cm] and positive lymph node metastatic ratio [100％ (5/5) vs.20％ (1/5)] (P ＜ 0.05).These MTC cases were followed-up for 7-66 months,postoperative calcitonin still positive in all 5 preoperatively symptomatic patients,while in only 1 preoperatively asymptomatic patient (P ＜ 0.05).PHEO was bilateral,multiple in 5 patients and unilateral multiple in 1 patient.Postoperatively 3 patients need lifelong steroid substitution.19-104 months follow-up found no recurrence or metastasis.RET screening showed a missense mutations of TGC to TAC (p.C634Y)at codon 634 on exon 11 in all 10 patients,and a patient was diagnosed as having de novo MEN2A.Conclusions Based on RET screening and serum calcitonin monitoring,early and radical surgery can cure MEN2A related MTC; One stage bilateral laparoscopic cortical-sparing adrenalectomy is recommended for bilateral PHEO in MEN2A patients. Key words: Multiple endocrine neoplasia type 2a; Thyroid neoplasms ; Pheochromocytoma; Proto-oncogene ; Point mutation