Calva Daniel, O'Dorisio Thomas M, Sue O'Dorisio M, Lal Geeta, Sugg Sonia, Weigel Ronald J, Howe James R
Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa College of Medicine, Iowa City, IA, USA.
Ann Surg Oncol. 2009 Aug;16(8):2237-44. doi: 10.1245/s10434-009-0524-3. Epub 2009 May 27.
Mutations in the RET proto-oncogene cause multiple endocrine neoplasia type 2A (MEN2A), and prophylactic thyroidectomy has generally been recommended before the age of 5 years. Patients with codon 609 mutations develop MTC at a later age and therefore the timing of prophylactic thyroidectomy is less clear. We report a three-generation family with C609Y RET mutation where members having prophylactic or therapeutic thyroidectomy call the current recommendations for age at thyroidectomy into question.
Sixteen family members underwent thyroidectomy, for which clinical, laboratory, and pathological data were analyzed. A literature review of RET codon 609 mutations was carried out.
Data were collected from 16 patients from this 38-member kindred. None of these affected members had pheochromocytoma, and one had a parathyroid adenoma. Nine of 16 patients had MTC (mean age 44.7 years, range 29-59 years) and elevated basal calcitonin levels; 6 of these 9 had lymph node metastases. Two patients had C-cell hyperplasia (CCH) at ages 18 and 37 years, and five patients had normal thyroid pathology (mean age 16 years, range 5-37 years). In the literature, a family with C609Y mutation was reported, with 15 members having MTC (mean age 42 years, range 21-59 years), and 6 with CCH (mean age 24 years, range 15-37 years).
The youngest patient with C609Y RET mutation and MTC was 21 years old, and the youngest patient with CCH was 15 years old at diagnosis. These data suggest that patients with RET C609Y mutations can delay thyroidectomy until 10-15 years of age, with annual calcitonin screening prior to thyroidectomy.
RET原癌基因突变可导致2A型多发性内分泌腺瘤病（MEN2A），一般建议在5岁前进行预防性甲状腺切除术。密码子609突变的患者发生甲状腺髓样癌（MTC）的年龄较晚，因此预防性甲状腺切除术的时机尚不清楚。我们报告了一个携带C609Y RET突变的三代家族，其中接受预防性或治疗性甲状腺切除术的成员对目前关于甲状腺切除术年龄的建议提出了质疑。
16名家族成员接受了甲状腺切除术，并对其临床、实验室和病理数据进行了分析。对RET密码子609突变进行了文献综述。
从这个38名成员的家族中收集了16名患者的数据。这些受影响的成员中没有一个患有嗜铬细胞瘤，有一名患有甲状旁腺腺瘤。16名患者中有9名患有MTC（平均年龄44.7岁，范围29 - 59岁）且基础降钙素水平升高；这9名患者中有6名有淋巴结转移。两名患者分别在18岁和37岁时出现C细胞增生（CCH），5名患者甲状腺病理正常（平均年龄16岁，范围5 - 37岁）。在文献中，报道了一个携带C609Y突变的家族，15名成员患有MTC（平均年龄42岁，范围21 - 59岁），6名患有CCH（平均年龄24岁，范围15 - 37岁）。
诊断时，携带C609Y RET突变且患有MTC的最年轻患者为21岁，患有CCH的最年轻患者为15岁。这些数据表明，携带RET C609Y突变的患者可以将甲状腺切除术推迟到10 - 15岁，在甲状腺切除术之前每年进行降钙素筛查。
