CAJ | 학술논문

目的对1例多发性内分泌腺瘤病2B型患者的临床特点、酪氨酸抑制剂治疗反应和致病基因进行探讨,以提高对此疾病的认识和治疗水平.方法收集患者长期诊治的临床资料、生化检查及影像学资料进行临床特点和药物治疗反应分析.抽取患者及其父母的外周静脉血,提取基因组DNA,通过聚合酶链反应(PCR)方法,对RET原癌基因第10 ～ 16个外显子及相邻内含子进行测序,明确RET基因突变状态.结果 (1)患者以甲状腺髓样癌(MTC)、双侧肾上腺嗜铬细胞瘤和多发黏膜神经纤维瘤为主要临床表现.(2) MTC,肺、肝和骨多处转移.病程中试用酪氨酸酶抑制剂——索拉非尼治疗MTC 2个月,水样腹泻和咳嗽减少.因不能耐受脱发、疼痛性皮疹不良反应而停药.(3)即使已发生肿瘤多处转移,但患者长期接受静脉营养支持治疗,存活时间超过14年.(4)基因检测示RET原癌基因存在激活突变,918位蛋氨酸被苏氨酸取代(Met 918 Thr).结论尽管手术是MTC主要治疗方式,但酪氨酸激酶抑制剂可能为晚期患者改善症状提供一个新选择.对已出现多处转移的患者,长期营养支持可能有助于延长生存时间.
목적 대1례다발성내분비선류병2B형환자적림상특점、락안산억제제치료반응화치병기인진행탐토,이제고대차질병적인식화치료수평.방법 수집환자장기진치적림상자료、생화검사급영상학자료진행림상특점화약물치료반응분석.추취환자급기부모적외주정맥혈,제취기인조DNA,통과취합매련반응(PCR)방법,대RET원암기인제10 ～ 16개외현자급상린내함자진행측서,명학RET기인돌변상태.결과 (1)환자이갑상선수양암(MTC)、쌍측신상선기락세포류화다발점막신경섬유류위주요림상표현.(2) MTC,폐、간화골다처전이.병정중시용락안산매억제제——색랍비니치료MTC 2개월,수양복사화해수감소.인불능내수탈발、동통성피진불량반응이정약.(3)즉사이발생종류다처전이,단환자장기접수정맥영양지지치료,존활시간초과14년.(4)기인검측시RET원암기인존재격활돌변,918위단안산피소안산취대(Met 918 Thr).결론 진관수술시MTC주요치료방식,단락안산격매억제제가능위만기환자개선증상제공일개신선택.대이출현다처전이적환자,장기영양지지가능유조우연장생존시간.
Objective To explore the clinical manifestations,therapeutic response and RET gene mutation in a patient with multiple endocrine neoplasia 2B (MEN2B) characterized by medullary thyroid carcinoma (MTC),bilateral adrenal pheochromocytoma and multiple mucosal neuromas.Methods The clinical features,laboratory data and radiological manifestations of this patient were collected.Genomic DNA was extracted from her peripheral blood leukocytes and her parents.Tenth to sixteenth exons of RET protooncogene,including the flanking regions of introns,were amplified by polymerase chain reaction (PCR).And the mutations of RET proto-oncogene were identified by direct sequencing.Results MEN-2B was diagnosed by the clinical presentations,laboratory tests and radiological findings.Gene analysis confirmed heterozygous mis-sense mutation at codon 918 in exon 16 of RET proto-oncogene in which thymine was replaced by cytosine (ATG→ACG).Her thyroid medullary carcinoma was treated by radical operations and radiotherapy.Tyrosinase inhibitor sorafenib was administered for 2 months and watery diarrhea and cough were alleviated.The drug was withdrawn because of such intolerant side effects as hair loss and painful rashes.She had a survival time of over 14 years with multiple system tumor metastases.Conclusions The mutation analysis of RET proto-oncogene confirmed the diagnosis of MEN2B in respect of molecular genetics.For patients with advanced MTC,tyrosinase inhibitors may relieve the symptoms and provide a new therapeutic choice.