Carney J A, Sizemore G W, Hayles A B
Pathobiol Annu. 1978;8:105-53.
Multiple endocrine neoplasia, type 2b, is a disorder of unknown etiology with major involvement of the thyroid and adrenal glands, the autonomic nervous system, and connective tissue. It is transmissible with an autosomal dominant pattern of inheritance, but since most cases are not familial, they presumably represent mutations. The thyroid gland exhibits bilateral medullary carcinoma, which is a metastasizing lethal neoplasm in the syndrome requiring total thyroidectomy once abnormal basal or stimulated concentrations of plasma immunoreactive calcitonin have been demonstrated. The adrenal medullary tumors--pheochromocytomas--although rarely malignant, are potentially lethal because of their cardiovascular effects. Since the adrenal involvement is usually bilateral, total bilateral adrenalectomy with excision of any extraadrenal paraganglioma is the surgical treatment. Parathyroid hyperplasia occurs rarely in the syndrome. Treatment of it should be conservative, that is, limited to excision of enlarged parathyroid glands. Major portions of the autonomic nervous system, both sympathetic and parasympathetic, nerves and ganglia, exhibit hypertrophy, hyperplasia, and disorder of structure--a group of changes designated ganglioneuromatosis. This may be largely responsible for the striking eye and oral findings--the hallmarks of the syndrome--and also for some of the serious symptoms and complications of the syndrome, particularly those referable to the alimentary tract. Ganglioneuromatosis is also found in the salivary glands, pancreas, gallbladder, upper respiratory tract, and urinary bladder. The connective tissue abnormality is manifested by increased growth of long bones, ribs, and skull, resulting in a marfanoid habitus, and also by skeletal and joint abnormalities together with increased laxity of ligaments. Ninety cases of MEN 2b have been reported, and although follow-up information is incomplete, 27 patients (30 percent) are known to be dead because of the syndrome. The causes of death have been medullary thyroid carcinoma (15 deaths), pheochromocytoma (10 deaths), and alimentary tract complications (2 deaths). An additional 21 patients (22 percent) are known to have metastatic MTC. We are aware of only 2 patients who, 5 years after thyroidectomy, have apparently been cured of MTC, but both are still at risk for adrenal medullary disease. MEN 2b is, therefore, a very serious disorder that requires urgent treatment of the endocrine tumors. Fortunately, the majority of patients with the syndrome are easily recognized because of an abnormal phenotype typified by thick, bumpy lips and a marfanoid habitus. Since these findings signal high risk for the potentially lethal endocrine neoplasms, patients having the characteristic appearance need evaluation of thyroidal C-cell and adrenal medullary function.
2b型多发性内分泌腺瘤病是一种病因不明的疾病，主要累及甲状腺、肾上腺、自主神经系统和结缔组织。它以常染色体显性遗传模式传递，但由于大多数病例并非家族性，推测它们代表突变。甲状腺表现为双侧髓样癌，在该综合征中这是一种转移性致死性肿瘤，一旦证实血浆免疫反应性降钙素的基础浓度或刺激浓度异常，就需要进行全甲状腺切除术。肾上腺髓质肿瘤——嗜铬细胞瘤——虽然很少恶变，但因其对心血管系统的影响而具有潜在致命性。由于肾上腺受累通常是双侧的，手术治疗是双侧肾上腺全切并切除任何肾上腺外副神经节瘤。甲状旁腺增生在该综合征中很少见。其治疗应采取保守方法，即仅限于切除增大的甲状旁腺。自主神经系统的主要部分，包括交感神经和副交感神经、神经和神经节，都表现出肥大、增生和结构紊乱——这一组变化被称为神经节瘤病。这可能在很大程度上导致了该综合征的显著眼部和口腔表现——该综合征的特征——以及该综合征的一些严重症状和并发症，特别是那些与消化道有关的症状和并发症。神经节瘤病也见于唾液腺、胰腺、胆囊、上呼吸道和膀胱。结缔组织异常表现为长骨、肋骨和颅骨生长增加，导致马方样体型，还表现为骨骼和关节异常以及韧带松弛增加。已报道90例2b型多发性内分泌腺瘤病病例，尽管随访信息不完整，但已知27例患者（30%）因该综合征死亡。死亡原因包括甲状腺髓样癌（15例死亡）、嗜铬细胞瘤（10例死亡）和消化道并发症（2例死亡）。另外21例患者（22%）已知患有转移性甲状腺髓样癌。我们只知道2例患者在甲状腺切除术后5年似乎已治愈甲状腺髓样癌，但两人仍有肾上腺髓质疾病的风险。因此，2b型多发性内分泌腺瘤病是一种非常严重的疾病，需要对内分泌肿瘤进行紧急治疗。幸运的是，大多数该综合征患者因异常表型（以嘴唇增厚、凹凸不平和马方样体型为典型）而容易被识别。由于这些表现预示着潜在致命性内分泌肿瘤的高风险，具有特征性外观的患者需要评估甲状腺C细胞和肾上腺髓质功能。
