遗传性甲状腺髓样癌MEN2A家系的临床诊治分析

Analysis of clinical diagnosis and treatment of a MEN2A pedigree with hereditary medullary thyroid carcinoma

目的探讨遗传性甲状腺髓样癌MEN2A家系的临床诊治特点。方法回顾性分析1个遗传性甲状腺髓样癌MEN2A家系的2例患者的临床资料,同时进行家系成员RET基因调查。结果第1例患者因"甲状腺髓样癌术后复发"入第三军医大学大坪医院(以下简称"我院")行右侧甲状腺残叶切除术+双侧颈部Ⅵ区淋巴结清扫术,术后第83天复查降钙素恢复正常。第2例患者在我院首次就诊后行甲状腺全切除术+双侧颈部Ⅵ区淋巴结清扫术,术后第47天复查降钙素恢复正常。2例患者术后均未出现声音嘶哑,甲状腺旁腺素随访2个月内均恢复正常。基因检测该家系为RET原癌基因第10外显子第611位点TGC-TAC杂合错义突变。系谱中发现第2代成员均患病,第3代成员中有50%的成员为携带RET突变基因的未发病者。结论根据临床表现可以确诊MEN2A,结合RET原癌基因突变筛查和进一步系谱调查可以早期诊断出无病RET突变基因携带者;通过家系调查,发现p.Cys611Tyr相关MEN2A家系属于国内首例,该疾病以甲状腺髓样癌和嗜铬细胞瘤发病为特征,不伴有甲状旁腺功能亢进的表现。

Objective To investigate the clinical characteristics of MEN2 A patients with hereditary medullary thyroid carcinoma. Methods The clinical data of 2 members of a MEN2 A pedigree with hereditary medullary thyroid carcinoma was analyzed retrospectively, and RET genetic screening in all family members were performed. Results One patient received the residual right thyroid tissue and bilateral cervical Ⅵ lymph node dissection in Daping Hospital, Third Military Medical University（ ＂our hospital＂ for short） because of medullary thyroid cancer recurrence, the calcitonin level returned to normal at 83 days after surgery. Another patient received total thyroidectomy and bilateral cervical Ⅵlymph node dissection after the initial diagnosis was confirmed in our hospital, the calcitonin level returned to normal at 47 days after surgery. Neither of them appeared hoarseness or loss of voice and both parathyroid hormone returned to normal within 2 months after operation. RET genetic screening showed that heterozygous missense mutations of TGC to TAC at codon 611 on exon 10 in this pedigree. All two members of the second generation had developed medullary thyroid carcinoma, 50% member of the third generation was a asymptomatic RET carrier. Conclusion MEN2 A can be diagnosed according to clinical manifestations, asymptomatic RET carrier can be diagnosed early through RET genetic screening and further pedigree investigation. Through the investigation of the family, it is found that the p.Cys611 Tyr related MEN2 A family is the first one in China. The disease is characterized by medullary thyroid carcinoma and pheochromocytoma,not accompanied with the manifestations of hyperparathyroidism.