Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.
Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.
复制标题
DOI：
10.1016/s2213-8587(18)30336-x
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Baudin E
中科院分区：
文献类型：
--
作者：
Castinetti F;Waguespack SG;Machens A;Uchino S;Hasse-Lazar K;Sanso G;Else T;Dvorakova S;Qi XP;Elisei R;Maia AL;Glod J;Lourenço DM Jr;Valdes N;Mathiesen J;Wohllk N;Bandgar TR;Drui D;Korbonits M;Druce MR;Brain C;Kurzawinski T;Patocs A;Bugalho MJ;Lacroix A;Caron P;Fainstein-Day P;Borson Chazot F;Klein M;Links TP;Letizia C;Fugazzola L;Chabre O;Canu L;Cohen R;Tabarin A;Spehar Uroic A;Maiter D;Laboureau S;Mian C;Peczkowska M;Sebag F;Brue T;Mirebeau-Prunier D;Leclerc L;Bausch B;Berdelou A;Sukurai A;Vlcek P;Krajewska J;Barontini M;Vaz Ferreira Vargas C;Valerio L;Ceolin L;Akshintala S;Hoff A;Godballe C;Jarzab B;Jimenez C;Eng C;Imai T;Schlumberger M;Grubbs E;Dralle H;Neumann HP;Baudin E
多发性内分泌腺瘤2B型是一种罕见的综合征，主要由Met 918 Thr生殖系RET突变引起，并以甲状腺髓样癌、嗜铬细胞瘤和外分泌特征为特征。关于多发性内分泌腺瘤病2B型的自然病史的资料很少。我们的目的是提高对多发性内分泌腺瘤2B型的表型和自然史的认识，提高认识和改善检测。本研究是一项在携带Met 918 Thr RET变体的患者中进行的回顾性、多中心、国际研究，无年龄限制。该研究使用了来自全球48个中心的注册数据。从2016年5月1日至2018年5月31日检索了1970年至2016年随访的患者数据。我们的主要目标是确定总生存率，以及根据患者是否在1岁之前接受过早期甲状腺切除术确定甲状腺髓样癌特异性生存率。我们还评估了甲状腺髓样癌的缓解，嗜铬细胞瘤的发病率和治疗，以及内分泌外特征的发病率。纳入345例患者，其中338例（98%）接受了甲状腺切除术。总队列中有71例患者（21%）死亡，中位年龄为25岁（范围<1-59岁）。20例患者在1岁之前进行甲状腺切除术，18例患者中有15例（83%）获得长期缓解（即降钙素水平检测不到）（2例患者死于与甲状腺髓样癌无关的原因）。甲状腺髓样癌特异性生存曲线在1年前或1年后接受甲状腺切除术的患者之间没有显示任何显著差异（通过对数秩检验比较生存曲线：p=0·2;风险比0·35; 95% CI 0·07 - 1·74）。然而，在1岁之前和之后接受甲状腺切除术的患者之间的缓解状态存在显著差异（p<0.0001）。在1岁之前和之后接受甲状腺切除术的患者之间的缓解状态有显著差异（p<0.0001）。在其他318例1岁后接受甲状腺切除术的患者中，318例患者中有47例（15%）获得生化和结构缓解。313例患者中，156例（50%）在28岁时被诊断为双侧嗜铬细胞瘤。在31例患者中进行了保留肾上腺的手术：31例患者中有3例（10%）长期复发，而16例（62%）患者获得了正常的肾上腺功能。所有有可用数据的患者（n=287）至少有一个外内分泌特征，包括106/190例（56%）显示马凡样体型、粘膜神经瘤和胃肠道体征的患者。在不超过1岁时进行甲状腺切除术与治愈的高概率相关。现实情况是，大多数患有该综合征的儿童将在这个建议的年龄后被诊断出来。保留肾上腺的手术治疗多发性内分泌腺瘤2B型是可行的，并提供了一个很好的机会，正常的肾上腺功能。为了改善这些患者的预后，每个卫生保健提供者都必须了解这种罕见综合征的外内分泌体征和自然史。这项研究的意义包括提高对内分泌外症状的认识，并建议在1岁之前进行甲状腺切除术。没有。
Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1–59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0⋅35; 95% CI 0.07–1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. None.