*Department of General, Visceral and Vascular Surgery, University of Halle, Halle, Germany †Department of Surgery, Haukeland University Hospital, University of Bergen, Bergen, Norway ‡Department of Surgical Sciences, University of Bergen, Bergen, Norway §Medical Faculty, University of Oslo, Oslo, Norway ¶Central Laboratory, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Ann Surg. 2014 Apr;259(4):800-6. doi: 10.1097/SLA.0b013e3182a6f43a.
This investigation aimed at exploring the suitability of nonendocrine manifestations preceding medullary thyroid cancer (MTC) for early diagnosis of multiple endocrine neoplasia type 2B (MEN 2B).
MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for biochemical cure.
Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patients) M918T RET mutations were examined for signs and symptoms prompting MEN 2B.
All 3 patients with inherited mutations were diagnosed before the age of 1 year and cured of their C-cell disease. Among 41 patients with de novo mutations, MEN 2B was diagnosed in 12 patients after recognition of nonendocrine manifestations [intestinal ganglioneuromatosis (6 patients), oral symptoms (5 patients), ocular ("tearless crying") (4 patients), and skeletal stigmata (1 patient) alone or concomitantly]. In the remaining 29 patients with de novo mutations, the diagnosis of MEN 2B was triggered by symptomatic MTC (28 patients) or pheochromocytoma (1 patient). The former patients, being significantly (P < 0.001) younger (means of 5.3 vs 17.6 years) and having lower calcitonin levels (means of 115 vs 25,519 pg/mL), smaller tumors (67% vs 0% were ≤10 mm) and less often extrathyroidal extension (0% vs 81%), lymph node (42% vs 100%), and distant metastases (8% vs 79%), were biochemically cured more often (58% vs 0%).
MTC is curable in patients with de novo mutations when nonendocrine MEN 2B components are quickly appreciated and surgical intervention is performed before patients turn 4 years old.
本研究旨在探讨髓样甲状腺癌（MTC）发生前的非内分泌表现对于多发性内分泌腺瘤病 2B 型（MEN 2B）的早期诊断是否具有适用性。
MEN 2B 患者发生转移性 MTC 的风险较高，必须早期进行生化治愈。
对携带遗传性（3 例）和新生（41 例）M918TRET 突变的 44 例 MEN 2B 患者进行了提示 MEN 2B 的体征和症状检查。
3 例遗传性突变患者均在 1 岁前确诊，并治愈了其 C 细胞疾病。在 41 例新生突变患者中，12 例患者在出现非内分泌表现后诊断为 MEN 2B[肠神经节瘤病（6 例）、口腔症状（5 例）、眼部（“无泪哭泣”）（4 例）和骨骼标志（1 例）单独或同时出现]。在其余 29 例新生突变患者中，MEN 2B 的诊断是由有症状的 MTC（28 例）或嗜铬细胞瘤（1 例）引发的。前者患者明显（P<0.001）更年轻（平均年龄为 5.3 岁与 17.6 岁），降钙素水平更低（平均值分别为 115pg/ml 与 25519pg/ml），肿瘤更小（67%的肿瘤直径≤10mm，与 0%相比），甲状腺外延伸、淋巴结和远处转移更少见（分别为 0%、81%与 8%、100%和 79%），因此更常被治愈（58%与 0%）。
当快速认识到非内分泌性 MEN 2B 成分，并在患者 4 岁之前进行手术干预时，新生突变患者的 MTC 是可治愈的。
