Nagaoka Ryuta, Sugitani Iwao, Sanada Marie, Jikuzono Tomoo, Okamura Ritsuko, Igarashi Takehito, Akasu Haruki, Shimizu Kazuo
Department of Endocrine Surgery, Nippon Medical School.
J Nippon Med Sch. 2018;85(3):178-182. doi: 10.1272/jnms.JNMS.2018_85-26.
Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare syndrome mainly caused by RET918 germline mutations. MEN2B typically causes medullary thyroid carcinoma (MTC), pheochromocytoma, and unique physical characteristics including mucosal neuroma, distinctive facial appearance, and Marfanoid habitus. Most patients have abdominal symptoms such as bloating, intermittent constipation, and diarrhea. MTC is the most important determinant of mortality in patients with MEN2B. Establishing the diagnosis of MEN2B at a curative stage of MTC is crucial.
We have encountered four patients with MEN2B. Two were hereditary cases from the same family, and two were considered de novo cases with phenotypically normal parents. Mean age at diagnosis was 25.5 years (range, 13-39 years). Although all patients had shown mucosal neuroma on the lips and tongue, in addition to gastrointestinal symptoms from infancy, diagnoses were made from symptomatic MTC even for the hereditary patients (our index case was a 14-year-old girl, whose mother was subsequently diagnosed with advanced MTC). Genetic tests for RET mutations revealed the M918T mutation in all patients. Two patients developed pheochromocytoma, two died from distant metastases of MTC, and two received treatment for multiple metastases of MTC (one with vandetanib).
In our patients with MEN2B, prophylactic or early thyroidectomy could not be performed. The characteristic phenotype associated with MEN2B is almost always seen prior to detection of MTC or pheochromocytoma. Knowledge about the non-endocrine manifestations of MEN2B needs to be shared among pediatricians and gastroenterologists.
2B型多发性内分泌腺瘤病（MEN2B）是一种极为罕见的综合征，主要由RET918种系突变引起。MEN2B通常会导致甲状腺髓样癌（MTC）、嗜铬细胞瘤，以及独特的身体特征，包括黏膜神经瘤、独特的面部外观和类马凡体型。大多数患者有腹胀、间歇性便秘和腹泻等腹部症状。MTC是MEN2B患者死亡的最重要决定因素。在MTC的治愈阶段确立MEN2B的诊断至关重要。
我们遇到了4例MEN2B患者。其中2例为同一家族的遗传病例，2例被认为是新发病例，其父母表型正常。诊断时的平均年龄为25.5岁（范围13 - 39岁）。尽管所有患者除了自幼出现胃肠道症状外，嘴唇和舌头均有黏膜神经瘤，但即使是遗传患者，也是从有症状的MTC做出诊断（我们的索引病例是一名14岁女孩，其母亲随后被诊断为晚期MTC）。RET突变基因检测显示所有患者均有M918T突变。2例患者发生嗜铬细胞瘤，2例死于MTC远处转移，2例接受了MTC多发转移的治疗（1例使用凡德他尼）。
在我们的MEN2B患者中，无法进行预防性或早期甲状腺切除术。与MEN2B相关的特征性表型几乎总是在检测到MTC或嗜铬细胞瘤之前出现。儿科医生和胃肠病学家之间需要共享关于MEN2B非内分泌表现的知识。
