摘要
目的 探讨多发性内分泌腺瘤2A型（MEN2A）的临床诊治特点及RET基因检测的意义.方法 对1976年6月至2013年2月间诊治的1个MEN2A家系共21例家庭成员进行系统家系调查,提取外周血进行RET基因和血清基础降钙素（Ct）水平检测.结果 基因检测家系内共10例家庭成员存在RET基因第11外显子p.C634Y 突变（10/21）,与临床完全符合.10例MEN2A患者中,男8例,女2例.7例甲状腺髓样癌（MTC）首次平均诊断年龄34.3（21-55）岁;肿瘤平均最大直径2.8（0.8-3.7）cm,5例接受了不规范的甲状腺切术,2例接受双侧甲状腺切除＋改良的双侧颈部淋巴结清扫,其中1例同期伴发甲状腺乳头状癌.平均随访172.4（10-440）个月,术后4例血清Ct水平升高,3例正常.7例中3例伴发双侧肾上腺嗜铬细胞瘤（PHEO;2例同时,1例异时）,平均首次诊断年龄48.3（42-58）岁,肿瘤平均最大直径7.0（4.4-8.5）cm;均接受了保留肾上腺皮质功能的PHEO切除术.分别随访15、17、120个月,未发生肾上腺皮质功能低下和复发、转移.通过家系调查发现的其中3例无症状RET基因突变携带者,平均年龄11.7（8-15）岁,均已随访17个月,Ct水平仍均轻度升高,均拒绝手术.结论 提高对MEN2A的认识和认知水平,整合临床筛查和RET基因检测,有利于MEN2A的及早诊断和规范化治疗,可减少手术并发症和提高远期治愈率.
Objective To screen the RET gene mutation in a pedigree of multiple endocrine neoplasia type 2A （MEN2A）. Methods Clinical data of 21 members in a MEN2A family were collected from June 1976 to February 2013. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening were performed. Results RET screening showed heterozygous missense mutations of cysteine to tyrosine at codon 634 on exon 11 in 10 MEN2A patients （ p. C63dY, 10/21 ） including 8 males and 2 females, which were completely consistent with the clinical manifestations. There were 7 patients with medullary thyroid carcinoma （ MTC ）, including one with concurrent papillary thyroid carcinoma. The mean age at onset was 34. 3 years （range： 21 -55 ）, and the mean maximum diameter of MTC was 2. 8 cm （ range ：0. 8 - 3.7）. Five patients underwent non-normative thyroidectomy, 2 patients underwent total thyroidectomy with modified bilateral neck dissection. The mean follow-up period for MTC was 172.4 months （range： 10 -440）, elevating calcitonin level was found in 4 patients, normal calcitonin level in 3 of the 7 patients, 3 were combined with bilateral pheochromocytoma （2 synchronous and 1 metachronous） , the mean age at onset was 48.3 years （range： 42 -58）, the maximum diameter of pheochromocytoma was 7.0 cm （ range ： 4. 4 - 8.5 ）. All 3 patients underwent bilateral （2 synchronous, 1 metachronous） cortical-sparing adrenalectomy, none of whom needed long-term steroid replacement and developed Addisonian crisis during the observation period （followed for 15, 17 and 120 months, respectively）. Three asymptomatic carriers with a mean age of 11.7 （ range ： 8 - 15）, rejected surgery and were closely monitored （followed for up to 17 months）. The carries had a slightly elevated calcitonin and 1 presented bilateral thyroid minimal lesions （ 0. 2 cm ）. Conclusions Screening of RET-mutation in MEN2A pedigree is helpful for early diagnosis, normative treatment, reducing complications and improve the long-term outcome of MEN2A.
出处
《中华全科医师杂志》
2014年第2期111-115,共5页
Chinese Journal of General Practitioners
基金
南京军区医学科技创新课题基金重点项目 （09Z038,10Z036）
关键词
多发性内分泌腺瘤2a型
癌
髓样
甲状腺
嗜铬细胞瘤
肾上腺
原癌基因
RET
Multiple endocrine neoplasia type 2a
Carcinoma, medullary
Thyroid gland
Pheochromocytoma, adrenal glands
Proto-oncogene, RET
