中华内分泌外科杂志
中華內分泌外科雜誌
중화내분비외과잡지
CHINESE JOURNAL OF ENDOCRINE SURGERY
2014年
2期
145-149
,共5页
赵坚强%戚晓平%楼建林%陈振光%郭良%余秀华%陈波%金杭阳%应荣彪%王可敬%韩春%张咸宁
趙堅彊%慼曉平%樓建林%陳振光%郭良%餘秀華%陳波%金杭暘%應榮彪%王可敬%韓春%張鹹寧
조견강%척효평%루건림%진진광%곽량%여수화%진파%금항양%응영표%왕가경%한춘%장함저
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
多髮性內分泌瘤2A型%髓樣癌%RET原癌基因%預防性甲狀腺切除術
다발성내분비류2A형%수양암%RET원암기인%예방성갑상선절제술
Multiple endocrine neoplasia type 2A%Medullary thyroid carcinoma%RET proto-onco-gene%Prophylactic thyroidectomy
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。
目的：探討多髮性內分泌腺瘤2A型（multiple endocrine neoplasia type 2A，MEN 2A）傢繫篩查的臨床意義和進行預防性甲狀腺全切除的可行性和有效性。方法對一箇MEN 2A傢繫行傢繫調查，提取外週血行RET原癌基因和降鈣素檢測，併對無癥狀的基因突變攜帶者行預防性甲狀腺全切除術。結果基因檢測該傢繫為RET原癌基因第11外顯子第634位點TGC→CGC雜閤錯義突變，即p．C634R突變，與MEN 2A患者臨床錶型-甲狀腺髓樣癌（ medullary thyroid carcinoma ，MTC）或MTC伴腎上腺嗜鉻細胞瘤（ pheochromocytom ，PHEO）完全共分離。6例MEN 2A中，男4例，女2例；首次診斷平均年齡33.5（19～65）歲；MTC平均直徑2.3（0.7～5.2）cm。其中3例以頸部佔位或伴腹瀉就診，接受瞭不規範的甲狀腺切除術或＋雙側Ⅵ區淋巴結清掃或＋側頸部淋巴結清掃；T2N1bM02例，T3N1bM01例。3例無癥狀者中2例行預防性甲狀腺切除＋雙側Ⅵ區淋巴結清掃，另1例行雙側甲狀腺全切除＋雙側Ⅵ區淋巴結清掃＋右側頸淋巴結清掃術；T1N0M02例，T1N1bM01例。僅見1例無癥狀者伴髮左側PHEO（1/6）併優先于MTC接受瞭左側PHEO切除。6例術後4例降鈣素仍升高，其中有癥狀中的1例（ T3N1bM0）先後接受瞭4次頸部手術，仍于首次術後130箇月齣現多處骨轉移伴骨痛（T3N1bM1），服用範得他尼2箇月後骨痛消失，至今帶瘤生存32箇月；另外有癥狀和無癥狀者各1例（T2N1bM0和T1N1bM0），分彆在首次術後6、7箇月接受瞭再次手術，包括另1例未再次手術的有癥狀者（T2N1bM0），3例至今分彆已22、22和20箇月，降鈣素仍升高。其餘2例無癥狀患者（T1N0M0）術後已隨訪20箇月，降鈣素均＜2.0 ng/L。結論對MEN 2A傢繫進行臨床篩查，有利于早期診斷和治療，改善預後；術前整閤RET基因和降鈣素檢測，對無癥狀基因突變攜帶者進行預防性全甲狀腺切除是可行、有效的。
목적：탐토다발성내분비선류2A형（multiple endocrine neoplasia type 2A，MEN 2A）가계사사적림상의의화진행예방성갑상선전절제적가행성화유효성。방법대일개MEN 2A가계행가계조사，제취외주혈행RET원암기인화강개소검측，병대무증상적기인돌변휴대자행예방성갑상선전절제술。결과기인검측해가계위RET원암기인제11외현자제634위점TGC→CGC잡합착의돌변，즉p．C634R돌변，여MEN 2A환자림상표형-갑상선수양암（ medullary thyroid carcinoma ，MTC）혹MTC반신상선기락세포류（ pheochromocytom ，PHEO）완전공분리。6례MEN 2A중，남4례，녀2례；수차진단평균년령33.5（19～65）세；MTC평균직경2.3（0.7～5.2）cm。기중3례이경부점위혹반복사취진，접수료불규범적갑상선절제술혹＋쌍측Ⅵ구림파결청소혹＋측경부림파결청소；T2N1bM02례，T3N1bM01례。3례무증상자중2례행예방성갑상선절제＋쌍측Ⅵ구림파결청소，령1례행쌍측갑상선전절제＋쌍측Ⅵ구림파결청소＋우측경림파결청소술；T1N0M02례，T1N1bM01례。부견1례무증상자반발좌측PHEO（1/6）병우선우MTC접수료좌측PHEO절제。6례술후4례강개소잉승고，기중유증상중적1례（ T3N1bM0）선후접수료4차경부수술，잉우수차술후130개월출현다처골전이반골통（T3N1bM1），복용범득타니2개월후골통소실，지금대류생존32개월；령외유증상화무증상자각1례（T2N1bM0화T1N1bM0），분별재수차술후6、7개월접수료재차수술，포괄령1례미재차수술적유증상자（T2N1bM0），3례지금분별이22、22화20개월，강개소잉승고。기여2례무증상환자（T1N0M0）술후이수방20개월，강개소균＜2.0 ng/L。결론대MEN 2A가계진행림상사사，유리우조기진단화치료，개선예후；술전정합RET기인화강개소검측，대무증상기인돌변휴대자진행예방성전갑상선절제시가행、유효적。
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 dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .
