Toledo Sergio Pereira de Almeida, dos Santos Marcelo Augusto Cortina Gonçalves, Toledo Rodrigo de Almeida, Lourenço Delmar Muniz
Genetic Endocrinology Unit (LIM-25), Internal Medicine Department, São Paulo University Medical School, São Paulo/SP, Brazil.
Clinics (Sao Paulo). 2006 Feb;61(1):59-70. Epub 2006 Mar 10.
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia type 2 is still an underdiagnosed, or late-diagnosed condition in many areas of the world. Since 1993, when the first missense RET proto-oncogene (RET) mutations were reported in MEN2, up to 46 different RET-causing disease mutations have been described. Since a strong genotype-phenotype correlation exists for MEN2, the detection of RET mutations has produced a major impact in early recognition and treatment of MTC and MEN2. Presently, RET mutation analysis should be performed for all MEN2 cases and their at-risk familial relatives. Further, prophylactic total thyroidectomy is indicated in all cases harboring activating gametic RET mutations. In most RET mutation carriers, prophylactic total thyroidectomy is indicated at ages as early as a few months to 4 years of age, promoting longer survival and improvement of quality of life or even definitive cure. We discuss the large impact of RET proto-oncogene analysis on the clinical management of MEN2 and the role of early RET molecular DNA diagnosis in providing clinicians and surgeons with valuable information that enables them to indicate early total thyroidectomy.
2型多发性内分泌腺瘤病（MEN2）是一种常染色体显性疾病，其特征为存在甲状腺髓样癌、原发性甲状旁腺功能亢进和嗜铬细胞瘤。在世界许多地区，2型多发性内分泌腺瘤病仍未得到充分诊断或诊断较晚。自1993年首次报道MEN2中存在错义RET原癌基因（RET）突变以来，已描述了多达46种不同的导致RET相关疾病的突变。由于MEN2存在很强的基因型与表型相关性，RET突变的检测对甲状腺髓样癌和MEN2的早期识别及治疗产生了重大影响。目前，应对所有MEN2病例及其有患病风险的家族亲属进行RET突变分析。此外，所有携带激活型配子RET突变的病例均应进行预防性全甲状腺切除术。在大多数RET突变携带者中，预防性全甲状腺切除术应在几个月至4岁的早期进行，以提高生存率、改善生活质量甚至实现根治。我们讨论了RET原癌基因分析对MEN2临床管理的重大影响，以及早期RET分子DNA诊断在为临床医生和外科医生提供有价值信息以指导早期全甲状腺切除术方面的作用。
