Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?
Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?
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DOI：
10.1089/thy.2019.0785
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发表时间：
2020-04-01
期刊：
影响因子：
6.6
通讯作者：
Niederle, Bruno
中科院分区：
文献类型：
--
作者：
Niederle, Martin B.;Scheuba, Christian;Niederle, Bruno
背景资料：进行基础（B）降钙素（CT）和钙（Ca）刺激CT（Ca-sCT）水平的测量，以在用作甲状腺结节诊断检查（CT筛查）的一部分时，在早期阶段识别甲状腺髓样癌（MTC）。在过去的十年中，已经引入了新的免疫荧光测定法，其对单体CT具有高度敏感性和特异性，并且避免了交叉反应。没有前瞻性生成的数据，迄今为止已成为回答经常提出的问题，是否钙-sCT相比，单独的bCT是有帮助的，因此，仍然表示为早期检测MTC.Methods：钙刺激试验进行了连续149例甲状腺结节和升高的bCT。无论Ca-sCT水平如何，所有患者均采用统一的手术方案进行手术，包括甲状腺切除术和系统性淋巴结清扫术。最近发表的分化MTC和其他C细胞病理（C细胞增生[CCH]）的性别特异性截止水平用于比较bCT或Ca-sCT单独和联合使用受试者工作特征（ROC）分析的诊断性能。此外，与Ca-sCT相比，评估了bCT预测外侧淋巴结转移的CT截止水平。结果：76例（50.1%）患者中发现MTC，其中21例（27.6%）伴淋巴结转移，4例（5.3%）伴远处转移。使用预定义的临界水平，患者可以有效地细分为临界水平以上的MTC确诊组（100%）和临界水平以下的CCH和MTC显著重叠的组（灰色区域）（均归类为pT 1a;男性：19/58 [37.5%]，女性：7/41 [17.1%]）。ROC曲线下面积（AUC）在所有测试中均非常适合MTC的诊断。bCT的测定被证明是诊断男性MTC的上级方法（bCT的AUC：0.894; Ca-sCT的AUC：0.849）和女性（bCT：0.935; Ca-sCT：0.868），并且还用于诊断外侧室中的淋巴结转移（男性：bCT：0.925; Ca-sCT：0.810;女性：bCT：0.797; Ca-sCT：0.674）。结合两种测试并不能提高诊断的准确性。使用女性>85 pg/mL和男性>100 pg/mL的临界水平，诊断侧颈淋巴结转移的灵敏度为100%。低于这些临界水平，没有患者表现出持续或复发性疾病（中位数随访：46 [ +/- 27] months）。结论：预先定义的性别特异性bCT临界水平有助于早期检测MTC和预测侧颈淋巴结转移。Ca-sCT并未改善术前诊断。男性bCT水平>43和>100 pg/mL以及女性bCT水平>23和>85 pg/mL与建议患者和计划手术范围相关。
Background: Measurements of both basal (b) calcitonin (CT) and calcium (Ca)-stimulated CT (Ca-sCT) levels are performed to identify medullary thyroid cancer (MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules (CT screening). Novel immunochemiluminometric assays, which are highly sensitive and specific for monomeric CT and avoid cross-reactivity, have been introduced over the past decade. No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and, therefore, still indicated for the early detection of MTC.Methods: Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT. Regardless of Ca-sCT levels, all patients had an operation applying a uniform surgical protocol, including thyroidectomy and systematic lymph node dissection. Recently published sex-specific cutoff levels for the differentiation of MTC and other C-cell pathologies (C-cell hyperplasia [CCH]) were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic (ROC) analysis. In addition, CT cutoff levels to predict lateral lymph node metastasis were evaluated for bCT compared with Ca-sCT. Follow-up for all patients was documented and correlated with initial CT levels.Results: MTC was identified in 76 (50.1%) patients, in 21/76 (27.6%) with lymph node and in 4 (5.3%) with distant metastasis. Using predefined cutoff levels, patients could effectively be subdivided into a group above the cutoff level with definitive diagnosis of MTC (100%) and below (gray zone) with a significant overlap of CCH and MTC (all classified as pT1a; males: 19/58 [37.5%], females: 7/41 [17.1%]). The areas under the ROC curve (AUC) were excellent for the diagnosis of MTC in all tests. Determination of bCT proved to be superior for both diagnosing MTC in males (AUC for bCT: 0.894; AUC for Ca-sCT: 0.849) and females (bCT: 0.935; Ca-sCT: 0.868) and also for diagnosing lymph node metastasis in the lateral compartment (males: bCT: 0.925; Ca-sCT: 0.810; females: bCT: 0.797; Ca-sCT: 0.674). Combining both tests did not improve diagnostic accuracy. Using a cutoff level of >85 pg/mL for females and >100 pg/mL for males, the sensitivity for diagnosing lateral neck lymph node metastasis was 100%. Below these cutoff levels, no patient showed persistent or recurrent disease (median follow-up: 46 [ +/- 27] months).Conclusions: Predefined sex-specific bCT cutoff levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis. Ca-sCT did not improve preoperative diagnostics. bCT levels >43 and >100 pg/mL for males and of >23 and >85 pg/mL for females are relevant for advising patients and planning the extent of surgery.