Raue Friedhelm, Bruckner Thomas, Frank-Raue Karin
Endocrine Practice, Heidelberg, Germany; Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Dtsch Arztebl Int. 2024 Oct 4;121(20):657-664. doi: 10.3238/arztebl.m2024.0174.
The cure rate of patients with hereditary medullary thyroid carcionoma (MTC) can be decisively improved by screening for elevated calcitonin (Ctn) levels and RET gene mutations in patients from families affected by multiple endocrine neoplasia type 2 (MEN2), followed by prophylactic thyroidectomy in persons with mutated RET genes. In this long-term observational study, we investigated whether postoperative cures are indeed maintained decades after the procedure.
From 1979 to 2021, 277 patients with MEN2 who underwent thyroidectomy were observed postoperatively for 14.4 ± 10.3 years (mean, standard deviation). They were classified as either cured or not cured depending on the last measured serum Ctn level (cured, Ctn < 10 pg/mL or < 2 pg/mL; not cured, Ctn ≥ 10 pg/mL). Depending on their RET mutation status, they were categorized as moderate, high, or highest risk (121, 130, and 26 patients, respec - tively).
154 patients (55.6%) obtained a long-term cure (Ctn <10 pg/mL). The median age at surgery was 27, 14, and 4 years in patients at moderate, high, and highest risk. All 52 patients who had undergone prophylactic thyroidectomy before the age of 6 years, 9 years, or 6 months had a Ctn level below 2 pg/mL and were cured at the end of the follow-up period. In a multivariable analysis, prognostic factors for a long-term cure were a lower tumor stage and, by tendency, classification as belonging to the moderate as opposed to the highest-risk group.
In patients receiving an early diagnosis of MEN2 via family screening, prophylactic thyroidectomy taking into account the RET mutation risk group can achieve a long-term cure of MTC with undetectable serum Ctn levels.
对于患有2型多发性内分泌腺瘤病（MEN2）的家族中的患者，通过筛查降钙素（Ctn）水平升高和RET基因突变，然后对RET基因发生突变的患者进行预防性甲状腺切除术，可以决定性地提高遗传性甲状腺髓样癌（MTC）患者的治愈率。在这项长期观察性研究中，我们调查了手术后数十年是否确实能维持治愈效果。
1979年至2021年，对277例接受甲状腺切除术的MEN2患者进行了术后14.4±10.3年（均值，标准差）的观察。根据最后一次测量的血清Ctn水平将他们分为治愈或未治愈（治愈，Ctn<10 pg/mL或<2 pg/mL；未治愈，Ctn≥10 pg/mL）。根据他们的RET突变状态，将他们分为中度、高度或最高风险组（分别为121、130和26例患者）。
154例患者（55.6%）获得了长期治愈（Ctn<10 pg/mL）。中度、高度和最高风险组患者手术时的中位年龄分别为27岁、14岁和4岁。所有在6岁、9岁或6个月之前接受预防性甲状腺切除术的52例患者，其Ctn水平均低于2 pg/mL，并且在随访期结束时被治愈。在多变量分析中，长期治愈的预后因素是较低的肿瘤分期，并且从趋势上看，是属于中度风险组而非最高风险组。
对于通过家族筛查早期诊断为MEN2的患者，考虑RET突变风险组进行预防性甲状腺切除术可以实现血清Ctn水平检测不到的MTC的长期治愈。
