CAJ | 학술논문

目的探讨3个多发性内分泌腺瘤2A型(MEN2A)家系的诊治及RET基因检测的临床意义.方法分析1990年4月至2011年12月诊治的3个家系10例MEN2A患者的临床资料.男4例,女6例.5例以颈部占位就诊:3例接受了不规范的甲状腺全切除术,2例接受双侧甲状腺全切+双侧颈部改良淋巴结清扫；5例无甲状腺肿瘤症状的RET基因突变携带者行双侧甲状腺全切+至少双侧颈部Ⅵ区淋巴结清扫.6例伴发肾上腺嗜铬细胞瘤(PHEO):5例行双侧PHEO一期切除,1例行单侧PHEO切除.3个家系共23例成员接受外周血RET基因检测.结果病理均明确诊断双侧甲状腺髓样癌(10/10).有、无症状的甲状腺髓样癌(MTC)患者间的首次平均诊断年龄[39.0(31 ～64)岁比18.2(5.5 ～36)岁]、肿瘤最大直径[2.8(1.2～5.6) cm比0.7(0.2 ～ 1.3) cm]、淋巴结阳性转移率[100％ (5/5)比20％ (1/5)],差异均有统计学意义(均P＜0.05).MTC随访7～ 66个月,术后降钙素有症状组均升高(5/5),无症状组仅见1例升高(P＜0.05).6例PHEO(60％)的平均诊断年龄42.0岁,5例为双侧多发,1例为单侧单发；3例双侧PHEO术后需终生口服激素替代.PHEO随访19 ～ 104个月,6例均无复发或转移.基因检测均为RET基因p.C634Y突变(10/23),1个家系为RET基因p.C634Y新发突变(de novo).结论基于RET基因和血清降钙素检测及早进行规范手术可有效治愈MEN2A-MTC；对伴有双侧PHEO者,应优先选择保留肾上腺皮质功能的腹腔镜下双侧PHEO一期切除术.
목적 탐토3개다발성내분비선류2A형(MEN2A)가계적진치급RET기인검측적림상의의.방법 분석1990년4월지2011년12월진치적3개가계10례MEN2A환자적림상자료.남4례,녀6례.5례이경부점위취진:3례접수료불규범적갑상선전절제술,2례접수쌍측갑상선전절+쌍측경부개량림파결청소；5례무갑상선종류증상적RET기인돌변휴대자행쌍측갑상선전절+지소쌍측경부Ⅵ구림파결청소.6례반발신상선기락세포류(PHEO):5례행쌍측PHEO일기절제,1례행단측PHEO절제.3개가계공23례성원접수외주혈RET기인검측.결과 병리균명학진단쌍측갑상선수양암(10/10).유、무증상적갑상선수양암(MTC)환자간적수차평균진단년령[39.0(31 ～64)세비18.2(5.5 ～36)세]、종류최대직경[2.8(1.2～5.6) cm비0.7(0.2 ～ 1.3) cm]、림파결양성전이솔[100％ (5/5)비20％ (1/5)],차이균유통계학의의(균P＜0.05).MTC수방7～ 66개월,술후강개소유증상조균승고(5/5),무증상조부견1례승고(P＜0.05).6례PHEO(60％)적평균진단년령42.0세,5례위쌍측다발,1례위단측단발；3례쌍측PHEO술후수종생구복격소체대.PHEO수방19 ～ 104개월,6례균무복발혹전이.기인검측균위RET기인p.C634Y돌변(10/23),1개가계위RET기인p.C634Y신발돌변(de novo).결론 기우RET기인화혈청강개소검측급조진행규범수술가유효치유MEN2A-MTC；대반유쌍측PHEO자,응우선선택보류신상선피질공능적복강경하쌍측PHEO일기절제술.
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.