儿童多发性内分泌腺瘤病2型中的预防性甲状腺切除术：单机构病例系列

文献信息

中文摘要

目的： 描述在一家四级儿科机构接受预防性全甲状腺切除术（PT）的儿童多发性内分泌腺瘤病2型（MEN2）患者的围手术期和术后结局，重点关注术后低钙血症、甲状旁腺功能减退症和重大手术并发症。
研究设计： 回顾性单机构病例系列。
地点： 四级儿童医院（田纳西州纳什维尔范德比尔特门罗·卡雷尔儿童医院）。
方法： 回顾2006年10月至2023年6月期间接受PT的所有年龄≤17岁的MEN2患者的病历。提取人口学、遗传学、围手术期和术后数据。主要结局为术后生化性低钙血症（血清钙<8.0 mg/dL或离子钙<4.0 mg/dL）。次要结局包括永久性甲状旁腺功能减退症、喉返神经（RLN）损伤和其他手术并发症。进行探索性年龄分层分析，以评估手术时年龄较小是否与并发症风险增加相关。
结果： 共纳入20例患者（中位年龄6.30岁[IQR 4.38-9.75]；范围2.09-14.16；男性10例[50%]）。所有患者均为MEN2A；最常突变的密码子为620（n=9，45%），包括C620R（n=7）和C620F（n=2）。11例患者（55%）发生术后短暂性生化性低钙血症；无患者发生永久性甲状旁腺功能减退症。2例患者（10%）在最终病理中检出甲状腺髓样癌（MTC），两者术前均未怀疑恶性肿瘤。无RLN损伤、血肿或其他重大手术并发症病例。1例患者（5%）出现短暂性声音改变，并完全恢复。在探索性分析中，手术时年龄与术后低钙血症无关（低钙血症组与非低钙血症组中位年龄分别为6.55岁与6.05岁；p=0.82），年龄≤5岁的患者低钙血症发生率并不高于年龄较大的患者（57% vs 54%；Fisher精确检验p=1.0）。
结论： 儿童MEN2中的PT可以以较低的永久性手术并发症发生率实施，包括在5岁及以下儿童中。短暂性低钙血症发生在大多数患者中，但均为自限性，且无患者发生永久性甲状旁腺功能减退症。10%的病例发现隐匿性MTC，强化了预防性干预的肿瘤学依据。这些发现支持全面的术前家庭咨询，强调短暂性电解质紊乱的可能性，同时向家庭保证永久性后遗症罕见。

英文摘要

OBJECTIVE: To characterize perioperative and postoperative outcomes in children with multiple endocrine neoplasia type 2 (MEN2) who underwent prophylactic total thyroidectomy (PT) at a single quaternary-care pediatric institution, with emphasis on postoperative hypocalcemia, hypoparathyroidism, and major surgical complications.
STUDY DESIGN: Retrospective single-institution case series.
SETTING: Quaternary-care children's hospital (Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee).
METHODS: Medical records of all patients aged ≤17 years with MEN2 who underwent PT between October 2006 and June 2023 were reviewed. Demographic, genetic, perioperative, and postoperative data were extracted. The primary outcome was postoperative biochemical hypocalcemia (serum calcium< 8.0 mg/dL or ionized calcium< 4.0 mg/dL). Secondary outcomes included permanent hypoparathyroidism, recurrent laryngeal nerve (RLN) injury, and other surgical complications. Exploratory age-stratified analyses were performed to assess whether younger age at surgery was associated with increased complication risk.
RESULTS: Twenty patients were included (median age 6.30 years [IQR 4.38-9.75]; range 2.09-14.16; 10 male [50%]). All patients had MEN2A; the most frequently mutated codon was 620 (n = 9, 45%), including C620R (n = 7) and C620F (n = 2). Eleven patients (55%) developed transient postoperative biochemical hypocalcemia; no patients developed permanent hypo-parathyroidism. Two patients (10%) had medullary thyroid carcinoma (MTC) identified on final pathology, neither of whom had suspected malignancy preoperatively. There were no cases of RLN injury, hematoma, or other major surgical complications. One patient (5%) experienced transient voice changes that resolved completely. In exploratory analyses, age at surgery was not associated with postoperative hypocalcemia (median age 6.55 vs. 6.05 years, hypocalcemia vs. no hypocalcemia; p = 0.82), and patients aged ≤5 years did not have a higher rate of hypocalcemia than older patients (57% vs. 54%; Fisher exact p = 1.0).
CONCLUSION: PT in pediatric MEN2 can be performed with a low rate of permanent surgical morbidity, including in children aged five years and younger. Transient hypocalcemia occurred in the majority of patients but was universally self-limited, and no patient developed permanent hypoparathyroidism. Occult MTC was identified in 10% of cases, reinforcing the oncologic rationale for prophylactic intervention. These findings support comprehensive preoperative family counseling emphasizing the likelihood of transient electrolyte disturbances while reassuring families regarding the rarity of permanent sequelae.