Skinner M A, Wells S A
Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Semin Pediatr Surg. 1997 Aug;6(3):134-40.
Medullary thyroid carcinoma (MTC) is an uncommon neoplasm in children that usually is associated with the multiple endocrine neoplasia (MEN) syndrome types 2A and 2B and with familial medullary thyroid carcinoma (FMTC). Recently, germline mutations in the RET proto-oncogene have been found in patients with these syndromes. Thus, with direct DNA testing, kindred members with MEN 2A, MEN 2B, or FMTC can be identified before clinical of biochemical evidence of MTC develops. It has been hypothesized that prophylactic thyroidectomy early in childhood, based on a positive genetic test, produces a better clinical outcome than thyroidectomy at the time MTC is diagnosed either clinically or biochemically. In the present report, the Washington University experience with MTC in children with MEN 2A and 2B is reviewed. Sixteen patients with MEN 2A who had thyroidectomy based on the biochemical diagnosis of MTC are compared with 14 children with MEN 2A who underwent prophylactic thyroidectomy based on direct genetic testing. In addition, the clinical results of 11 patients with MEN 2B treated for MTC are reviewed. After 3 years of follow-up there has been no biochemical or clinical evidence of MTC among the 14 children who had prophylactic thyroidectomy. Among the 16 children with MEN 2A who had thyroidectomy because of elevated basal of stimulated calcitonin levels, four (25%) have persistent of recurrent MTC after a mean follow-up period of 7.6 years. Of the 11 patients with MEN 2B who underwent thyroidectomy during childhood, one has died and seven (70%) of the remaining patients have recurrent MTC after a mean follow-up period of 11 years. The authors conclude that a significant number of children with MEN 2A or MEN 2B, who have clinical of biochemical evidence of MTC before thyroidectomy, have persistent or recurrent disease after long-term clinical follow-up. The diagnosis by direct DNA testing in patients with these syndromes allows prophylactic thyroidectomy before the development of extensive local or metastatic MTC.
甲状腺髓样癌（MTC）在儿童中是一种罕见的肿瘤，通常与2A和2B型多发性内分泌腺瘤病（MEN）综合征以及家族性甲状腺髓样癌（FMTC）相关。最近，在患有这些综合征的患者中发现了RET原癌基因的种系突变。因此，通过直接DNA检测，可以在MTC出现临床或生化证据之前识别出患有MEN 2A、MEN 2B或FMTC的亲属成员。据推测，基于基因检测阳性在儿童早期进行预防性甲状腺切除术，比在MTC临床或生化诊断时进行甲状腺切除术能产生更好的临床结果。在本报告中，回顾了华盛顿大学对患有MEN 2A和2B的儿童MTC的治疗经验。将16例基于MTC生化诊断而接受甲状腺切除术的MEN 2A患者与14例基于直接基因检测而接受预防性甲状腺切除术的MEN 2A儿童进行比较。此外，还回顾了11例接受MTC治疗的MEN 2B患者的临床结果。经过3年的随访，14例接受预防性甲状腺切除术的儿童中没有MTC的生化或临床证据。在16例因基础或刺激降钙素水平升高而接受甲状腺切除术的MEN 2A儿童中，4例（25%）在平均随访7.6年后出现持续性或复发性MTC。在11例儿童期接受甲状腺切除术的MEN 2B患者中，1例死亡，其余7例（70%）在平均随访11年后出现复发性MTC。作者得出结论，相当数量的在甲状腺切除术前行MTC临床或生化检查的MEN 2A或MEN 2B儿童，在长期临床随访后出现持续性或复发性疾病。对这些综合征患者进行直接DNA检测可在广泛的局部或转移性MTC发生之前进行预防性甲状腺切除术。
