多发性内分泌腺瘤2A 型家系的临床筛查及预防性甲状腺全切除术  

Pedigree screening of a Chinese multiple endocrine neoplasia type 2A family and prophylactic total thy-roidectomy

作　　者：赵坚强[1] 戚晓平[2] 楼建林[1] 陈振光[2] 郭良[1] 余秀华[2] 陈波[1] 金杭阳[2] 应荣彪[3] 王可敬[1] 韩春[1] 张咸宁 

机构地区：[1] 浙江省肿瘤医院头颈外科, 杭州310022 [2] 解放军第一一七医院肿瘤泌尿外科,杭州310004 [3] 解放军第一一七医院超声科,杭州10004 [4] 浙江省台州市肿瘤医院肿瘤外科, 台州317502

出　　处：《中华内分泌外科杂志》2014年第2期145-149,共5页Chinese Journal of Endocrine Surgery

基　　金：南京军区医学科技创新课题基金重点项目（092038、102036）

摘　　要：目的：探讨多发性内分泌腺瘤2A型（multiple endocrine neoplasia type 2A，MEN 2A）家系筛查的临床意义和进行预防性甲状腺全切除的可行性和有效性。方法对一个MEN 2A家系行家系调查，提取外周血行RET原癌基因和降钙素检测，并对无症状的基因突变携带者行预防性甲状腺全切除术。结果基因检测该家系为RET原癌基因第11外显子第634位点TGC→CGC杂合错义突变，即p．C634R突变，与MEN 2A患者临床表型-甲状腺髓样癌（ medullary thyroid carcinoma ，MTC）或MTC伴肾上腺嗜铬细胞瘤（ pheochromocytom ，PHEO）完全共分离。6例MEN 2A中，男4例，女2例；首次诊断平均年龄33.5（19～65）岁；MTC平均直径2.3（0.7～5.2）cm。其中3例以颈部占位或伴腹泻就诊，接受了不规范的甲状腺切除术或＋双侧Ⅵ区淋巴结清扫或＋侧颈部淋巴结清扫；T2N1bM02例，T3N1bM01例。3例无症状者中2例行预防性甲状腺切除＋双侧Ⅵ区淋巴结清扫，另1例行双侧甲状腺全切除＋双侧Ⅵ区淋巴结清扫＋右侧颈淋巴结清扫术；T1N0M02例，T1N1bM01例。仅见1例无症状者伴发左侧PHEO（1/6）并优先于MTC接受了左侧PHEO切除。6例术后4例降钙素仍升高，其中有症状中的1例（ T3N1bM0）先后接受了4次颈部手术，仍于首次术后130个月出现多处骨转移伴骨痛（T3N1bM1），服用范得他尼2个月后骨痛消失，至今带瘤生存32个月；另外有症状和无症状者各1例（T2N1bM0和T1N1bM0），分别在首次术后6、7个月接受了再次手术，包括另1例未再次手术的有症状者（T2N1bM0），3例至今分别已22、22和20个月，降钙素仍升高。其余2例无症状患者（T1N0M0）术后已随访20个月，降钙素均＜2.0 ng/L。结论对MEN 2A家系进行临床筛查，有利于早期诊断和治疗，改善预后；术前整合RET基因和降钙素检测，对无症状基因突变携带者进行预防性全甲状腺切除是可行、有效的�Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A（MEN 2A）family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma （ MTC）.Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members（p.C634R）, which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years（ranging from 19 years to 65 years） and the mean maximum diameter of MTC was 2.3 cm（ranging from 0.7 cm to 5.2 cm）. Among them 3 members had palpable neck masses （1 case with diarrhea）.Right total thyroidectomy ＋right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy ＋bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy ＋bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom （ PHEO） underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient（ T3N 1bM 0-1） underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively （T1N 1bM0 and T2N 1bM0）, and the other one patient was closely monitored and followed up for 22 months（T2N 1b M0）.Moreover, The calcitonin levels dropp

关 键 词：多发性内分泌瘤2A型 髓样癌 RET原癌基因 预防性甲状腺切除术 

分 类 号：R736[医药卫生—肿瘤]