RET突变的嗜铬细胞瘤患者的临床及基因特征

Clinical and genetic manifestation of pheochromocytoma patients with RET mutation

目的研究RET突变的嗜铬细胞瘤患者的临床及基因特征。方法回顾性分析北京协和医院2013—2019年诊治的23例RET突变的嗜铬细胞瘤患者的临床资料、实验室检查结果和RET突变位点信息。结果23例患者(男13例,女10例)嗜铬细胞瘤诊断年龄为(32±10)岁。多发性内分泌腺瘤病2A患者22例,突变集中RET外显子16(18例),以密码子634最常见(16例),其次为外显子10、14突变,1例多发性内分泌腺瘤病2B患者为RET外显子16的M918T突变。23例患者中阵发性高血压9例,持续性高血压5例,正常血压3例,有发作性心悸但发作时未测血压者6例。24 h尿儿茶酚胺:去甲肾上腺素65.8(36.9,235.9)μg/24 h,肾上腺素5.4(2.8,37.2)μg/24 h,多巴胺277(198,297)μg/24 h,15例患者有单项或多项升高,8例患者完全正常。肿瘤最大直径为4(3,6)cm。15例患者为双侧嗜铬细胞瘤,17例患者还患有甲状腺髓样癌。结论本组RET突变的嗜铬细胞瘤患者临床上多表现为阵发性高血压,部分患者尿儿茶酚胺测定正常,需要临床关注以免漏诊。

Objective To explore clinical and genetic manifestation of pheochromocytoma patients with RET gene mutation.Methods Clinical data,laboratory examination results and RET gene mutations of 23 pheochromocytoma patients with RET mutation treated in Peking Union Medical College Hospital from 2013 to 2019 were retrospectively analyzed.Results The diagnosis age of pheochromocytoma in 23 patients was 32±10 years.In 22 patients with multiple endocrine neoplasia(MEN)2A,mutations were clustered in exon 16(18 cases),especially in codon 634(16 cases),followed by exon 10 and 14,and one patient with MEN2B had M918T in exon 16.Among the 23 patients,9 had paroxysmal hypertension,5 had sustained hypertension,3 were normotensive,and 6 had episodic palpitations but their blood pressures were not measured during the attacks.24 h urinary catecholamineexcretion was as following:norepinephrine(NE):65.8(36.9,235.9)μg/24 h,Epinephrine(E):5.4(2.8,37.2)μg/24 h and Dopamine(DA):277(198,297)μg/24 h.15 patients had abnormally increased NE,E or DA,while 8 patients had normal catecholamine excretion.The median diameter of the tumors was 4(3,6)cm.Fifteen patients had bilateral pheochromocytoma and 17 had medullary thyroid carcinoma.Conclusions Pheochromocytoma patients with RET mutation are consistent with those reported in western countries in terms of age at diagnosis,tumor size and mutation profile.Most patients have paroxysmal hypertension or normal pressure,and some of them have normal urinary catecholamine excretion,which are potential risk factors of missed diagnosis.