CAJ | 학술논문

目的探讨多发性内分泌腺瘤2A型(MEN2A)中肾上腺嗜铬细胞瘤(PHEO)的临床特征及RET原癌基因突变检测的意义.方法收集分析1989年8月至2013年1月诊治的13个MEN2A家系32例PHEO患者的临床资料、家系谱,并进行RET基因检测分析.结果 13个MEN2A家系68例MEN2A患者中32例(47.1％)伴有PHEO,其中男19例,女13例；首次诊断年龄18～78岁,平均(41±12)岁；PHEO肿瘤最大直径2.5～11.0 cm,平均(4.6±2.2)cm；先诊断甲状腺髓样癌、后诊断PHEO的12例(37.5％),同时诊断的12例(37.5％),初始诊断为PHEO的7例(21.9％),阑尾切除术中PHEO诱发高血压危象死亡的1例(3.1％).临床筛查前确诊的22例PHEO中有PHEO症状者12例,筛查后发现的10例PHEO中仅1例有PHEO症状(12/22比1/10,P=0.024).除外死于非PHEO术中的5例无症状者,17例伴双侧PHEO(3例为异时双侧PHEO)患者中有症状者7例,10例伴单侧PHEO患者中有症状者6例(7/17比6/10,P=0.440).25例接受了PHEO手术:开放切除11例(双侧一期切除2例),腹腔镜下切除14例(双侧一期切除8例).术后10例需激素替代治疗.平均随访72(1～282)个月,2例出现肾上腺皮质功能低下表现,未见PHEO局部复发和远处转移.RET基因突变分属4种基因型,32例MEN2A-PHEO患者中31例(96.9％)为p.C634Y/R/F突变(来自12个家系)；1例(3.1％)为p.C618R突变(来自1个家系).结论 MEN2A-PHEO的RET基因突变大多位于第634位点.通过家系调查和RET基因检测,尤其有利于无症状PHEO的及早发现和治疗,可优先选择腹腔镜下行保留肾上腺皮质功能的肾上腺切除术.
목적 탐토다발성내분비선류2A형(MEN2A)중신상선기락세포류(PHEO)적림상특정급RET원암기인돌변검측적의의.방법 수집분석1989년8월지2013년1월진치적13개MEN2A가계32례PHEO환자적림상자료、가계보,병진행RET기인검측분석.결과 13개MEN2A가계68례MEN2A환자중32례(47.1％)반유PHEO,기중남19례,녀13례；수차진단년령18～78세,평균(41±12)세；PHEO종류최대직경2.5～11.0 cm,평균(4.6±2.2)cm；선진단갑상선수양암、후진단PHEO적12례(37.5％),동시진단적12례(37.5％),초시진단위PHEO적7례(21.9％),란미절제술중PHEO유발고혈압위상사망적1례(3.1％).림상사사전학진적22례PHEO중유PHEO증상자12례,사사후발현적10례PHEO중부1례유PHEO증상(12/22비1/10,P=0.024).제외사우비PHEO술중적5례무증상자,17례반쌍측PHEO(3례위이시쌍측PHEO)환자중유증상자7례,10례반단측PHEO환자중유증상자6례(7/17비6/10,P=0.440).25례접수료PHEO수술:개방절제11례(쌍측일기절제2례),복강경하절제14례(쌍측일기절제8례).술후10례수격소체대치료.평균수방72(1～282)개월,2례출현신상선피질공능저하표현,미견PHEO국부복발화원처전이.RET기인돌변분속4충기인형,32례MEN2A-PHEO환자중31례(96.9％)위p.C634Y/R/F돌변(래자12개가계)；1례(3.1％)위p.C618R돌변(래자1개가계).결론 MEN2A-PHEO적RET기인돌변대다위우제634위점.통과가계조사화RET기인검측,우기유리우무증상PHEO적급조발현화치료,가우선선택복강경하행보류신상선피질공능적신상선절제술.
Objective To explore the clinical patterns and clinical significance for RET screening in adrenal pheochromocytoma (PHEO) associated with multiple endocrine neoplasia type 2A (MEN2A).Methods The clinical data of 32 PHEO patients with MEN2A from 13 unrelated MEN2A pedigrees from August 1989 to January 2013 were analyzed.The comprehensive medical data included systemic examinations and germline RET gene screening.Results Among 68 patients belonging to 13 MEN2A families,32 (47.1％) presented with PHEO.There were 19 males and 13 females with a mean age of (41 ± 12) years.And the mean maximum diameter of PHEO was (4.6 ± 2.2) cm.The diagnosis of PHEO was made after medullary thyroid carcinoma (n =12,37.5％),simultaneously (n =12,37.5％),initially (n =7,21.9％) and death during appendectomy for PHEO-induced hypertensive crisis (n =1,3.1％).The diagnosis of PHEO was made before (n =22) or after (n =10) clinical screening.The former had 12 symptomatic cases while the latter only 1 case (12/22 vs 1/10,P =0.024).Except for 5 asymtomatic fatal cases during non-PHEO operations,bilateral PHEO was found in 17 cases including 3 unilaterally treated cases developing another PHEO in contralateral adrenal with a lag period of 5,10 and 17 years.There were 7 symptomatic patients in bilateral cases versus 6 in unilateral cases (7/17 vs 6/10,P =0.440).Twenty-five patients underwent PHEO surgery:laparascopic approach in 14 cases (8 with bilateral simultaneous adrenalectomy) and open approach in 11 (2 with bilateral simultaneous adrenalectomy).And 10 patients undergoing bilateral adrenal-sparing operations or adrenalectomy required hormonal replacement therapy.During a mean observation period of 72 (1-282) months,no local recurrence,distant metastasis or Addisonian crisis were noted in 25 cases (contralateral relapse in 3 cases).Among them,2 cases developed adrenocortical insufficiency unresponsive to an adjustment of hormonal doses.RET screening showed 4 recurrent missense substitutions in 32 MEN2A-PHEO patients:p.C634Y exon 11 (n =27,84.4％),p.C634R exon 11 (n =3,9.4％),p.C634F exon 11 (n =1,3.1％) and p.C618R exon 10 (n =1,3.1％).Conclusions The mutations of RET proto-oncognene of PHEO in MEN2A are frequently located at codon 634.A combination of pedigree examination and RET gene screening may facilitate an early diagnosis and early treatment of asymptomatic PHEO patients in MEN2A.Laparoscopic cortical-sparing adrenalectomy for preserving adrenocortical function is a preferred surgical approach.