O'Riordain D S, O'Brien T, Crotty T B, Gharib H, Grant C S, van Heerden J A
Department of Surgery, Mayo Clinic, Rochester, Minn 55905, USA.
Surgery. 1995 Dec;118(6):936-42. doi: 10.1016/s0039-6060(05)80097-2.
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disorder differentiated from MEN 2A primarily by its extraendocrine features. This report describes the clinical spectrum and outcome of MEN 2B.
Twenty-one patients underwent operation for manifestations of MEN 2B between 1970 and 1993. Median follow-up was 16.9 years. Diagnosis was made through family screening in nine, the development of medullary thyroid carcinoma (MTC) in seven, phenotypic features in four, and constipation in one. Median age at presentation of colonic dysfunction, MTC, and pheochromocytoma was 0.1, 16, and 28 years, respectively.
Every patient had MTC. Fifteen (94%) of 16 patients undergoing primary thyroidectomies had multicentric disease, and seven (44%) had nodal metastases. Seven patients (33%) had pheochromocytoma, six bilateral and one malignant. Adrenalectomy was curative in every patient. Nineteen patients (90%) had colonic disturbances, typically chronic constipation from birth. Megacolon developed in 14 patients, and eight required colonic surgery. Every patient had the characteristic phenotype. Dominant features included neuromas of the tongue, buccal mucosa, lips, conjunctivae, and eyelids and a marfanoid habitus. Other features included high arched palate, corneal nerve thickening, and dental and skeletal abnormalities. Four patients died, two of metastatic MTC, one after operation for metastatic MTC, and one as a consequence of colonic perforation. Of 17 survivors, three have hepatic metastases from MTC, eight have nodal metastases, and six are well with normal or mildly elevated calcitonin levels.
MEN 2B is characterized by a relatively aggressive form of MTC, bilateral pheochromocytoma, severe colonic dysfunction, and a multitude of other extraendocrine abnormalities. Early recognition of MEN 2B and early prophylactic thyroidectomy are essential. Colonic dysfunction has previously received little attention, and further investigation of the pathogenesis and treatment of this disorder is warranted.
2B型多发性内分泌腺瘤病（MEN 2B）是一种罕见的疾病，与2A型多发性内分泌腺瘤病的主要区别在于其内分泌外特征。本报告描述了MEN 2B的临床谱及预后。
1970年至1993年间，21例患者因MEN 2B的表现接受了手术。中位随访时间为16.9年。9例通过家族筛查确诊，7例因甲状腺髓样癌（MTC）进展确诊，4例因表型特征确诊，1例因便秘确诊。出现结肠功能障碍、MTC和嗜铬细胞瘤的中位年龄分别为0.1岁、16岁和28岁。
所有患者均患有MTC。16例行初次甲状腺切除术的患者中，15例（94%）有多中心疾病，7例（44%）有淋巴结转移。7例患者（33%）患有嗜铬细胞瘤，6例为双侧，1例为恶性。肾上腺切除术对每位患者均有疗效。19例患者（90%）有结肠功能障碍，通常自出生起就有慢性便秘。14例患者发生巨结肠，8例需要进行结肠手术。所有患者均有特征性表型。主要特征包括舌、颊黏膜、唇、结膜和眼睑的神经瘤以及类马凡体型。其他特征包括高拱腭、角膜神经增厚以及牙齿和骨骼异常。4例患者死亡，2例死于转移性MTC，1例在转移性MTC手术后死亡，1例因结肠穿孔死亡。17名幸存者中，3例有MTC肝转移，8例有淋巴结转移，6例情况良好，降钙素水平正常或轻度升高。
MEN 2B的特征是MTC相对侵袭性的形式、双侧嗜铬细胞瘤、严重的结肠功能障碍以及许多其他内分泌外异常。早期识别MEN 2B并早期进行预防性甲状腺切除术至关重要。结肠功能障碍此前很少受到关注，有必要对该疾病的发病机制和治疗进行进一步研究。
