开发并应用新型降钙素敏感免疫分析测定法在大样本量的甲状腺髓样癌和分化型甲状腺癌、甲状腺结节和自身免疫性甲状腺疾病患者中的应用。

Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases.

机构信息

Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.

Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil ; Fleury Medicine and Health, São Paulo, Brazil.

出版信息

Eur Thyroid J. 2014 Jun;3(2):117-24. doi: 10.1159/000363055. Epub 2014 Jun 18.

DOI:10.1159/000363055

PMID:25114875

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4109516/

Abstract

BACKGROUND

Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD).

OBJECTIVE AND METHODS

We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay.

RESULTS

The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC curve were 18.4 pg/ml for males and 7.8 pg/ml for females. sCT in patients with MTC was strongly correlated with disease status. Patients with NTD and ATD did not present false-positive results. sCT measurements were significantly correlated with age (excluding MTC and CRF). The NID test had a strong correlation with our assay. A hook effect was observed only with concentrations >200,000 pg/ml.

CONCLUSIONS

We developed a novel sCT assay and validated it in healthy subjects, as well as in a large cohort of patients with MTC, NTD, ATD, DTC, and CRF.

摘要

背景

血清降钙素（sCT）是甲状腺髓样癌（MTC）的有用生物标志物。对于结节性甲状腺疾病（NTD）的评估，sCT 测量尚未达成共识。

目的和方法

我们开发了一种新的 sCT 免疫荧光测定法，并在 794 名患者[203 名患有 MTC、205 名患有自身免疫性甲状腺疾病（ATD）、248 名患有 NTD、80 名患有分化型甲状腺癌（DTC）'无疾病'、58 名患有慢性肾功能衰竭（CRF）]和 178 名正常个体的样本中进行了验证，包括五肽胃泌素试验后的样本和来自 NTD 或 MTC 患者 92 次 FNA 程序洗脱的样本。我们还比较了一些使用该测定法和 Nichols Institute Diagnostics（NID）测定法的低或高降钙素水平患者的样本。

结果

该测定的分析灵敏度为 1.0 pg/ml。考虑到手术前的 MTC 患者，95%参考范围的截断值为男性 11.1 pg/ml，女性 5.5 pg/ml，使用 ROC 曲线为男性 18.4 pg/ml，女性 7.8 pg/ml。MTC 患者的 sCT 与疾病状态密切相关。NTD 和 ATD 患者未出现假阳性结果。sCT 测量与年龄显着相关（不包括 MTC 和 CRF）。NID 测试与我们的测试具有很强的相关性。仅在浓度>200,000 pg/ml 时观察到钩效应。