Department of Endocrinology, Waikato Hospital, Waikato, New Zealand.
Horm Metab Res. 2012 May;44(5):339-42. doi: 10.1055/s-0031-1295497. Epub 2012 Jan 24.
Multiple endocrine neoplasia type 2a results from an activating germline mutation in the RET proto-oncogene. Carriers of a RET mutation are at risk of medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. Most individuals with multiple endocrine neoplasia type 2a eventually develop medullary thyroid carcinoma and as there is a strong genotype-phenotype correlation, guidelines have been established as to the age recommended for prophylactic thyroidectomy. However for rare mutations in the RET proto-oncogene there is insufficient evidence to provide guidance as to the risk of medullary thyroid carcinoma. We present a family with the rare RET mutation, D631Y in which the proband initially presented with a pheochromocytoma, and review the available literature pertaining to this mutation. In 83% of index cases, pheochromocytoma was the presenting feature and only 37% of adult germline mutation carriers have developed medullary thyroid carcinoma, none of whom have been reported to have nodal or metastatic disease. Patients with a D631Y RET mutation typically present with pheochromocytoma and medullary thyroid carcinoma appears to occur with a later onset than reported with other RET mutations. Based on the current literature we recommend performing prophylactic total thyroidectomy by age 12 years for D631Y carriers although this recommendation may need to be reviewed as additional data becomes available.
多发性内分泌肿瘤 2a 型是由原癌基因 RET 的激活种系突变引起的。RET 突变携带者有发生甲状腺髓样癌、嗜铬细胞瘤和甲状旁腺功能亢进的风险。大多数多发性内分泌肿瘤 2a 型患者最终都会发生甲状腺髓样癌，由于存在很强的基因型-表型相关性，因此已经制定了预防性甲状腺切除术的推荐年龄指南。然而，对于 RET 原癌基因突变，缺乏足够的证据来提供关于甲状腺髓样癌风险的指导。我们报告了一个携带罕见 RET 突变 D631Y 的家族，该家族中的先证者最初表现为嗜铬细胞瘤，并回顾了与该突变相关的可用文献。在 83%的指数病例中，嗜铬细胞瘤是首发表现，只有 37%的成年种系突变携带者发生了甲状腺髓样癌，其中没有人报告有淋巴结或转移性疾病。携带 D631Y RET 突变的患者通常表现为嗜铬细胞瘤，甲状腺髓样癌的发生似乎比其他 RET 突变报告的时间晚。基于目前的文献，我们建议对 D631Y 携带者在 12 岁时进行预防性全甲状腺切除术，尽管随着更多数据的出现，可能需要对这一建议进行审查。
