摘要目的 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.

abstractsObjective 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.