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正常人血清中泌乳素(prolactin,PRL)有3种形式:相对分子质量为23 000单体泌乳素(monomeric prolactin,mono-PRL)、相对分子质量为40 000~60 000大泌乳素(big prolactin,big-PRL)以及相对分子质量为100 000巨泌乳素(macro prolactin,M-PRL)[1]。真性高泌乳素血症是指血液中高水平的mono-PRL和big-PRL引起的内分泌紊乱性疾病[2]。真性巨泌乳素血症(MP)病人血液中PRL以M-PRL为主,mono-PRL和big-PRL水平正常且无明显的临床症状[3]。M-PRL是PRL与其IgG型抗体结合形成的免疫复合物,因其相对分子质量大不能通过毛细血管壁,无法与靶细胞PRL受体结合,因而不能发挥出生物学效应[4-5],再加上其在体内的半衰期较长,易于在体循环中累积,可造成PRL浓度假性增高[6],进而导致不必要的检查及药物治疗,因此筛查并排除M-PRL的影响十分重要。目前实验室诊断MP主要方法为25%聚乙二醇(PEG)沉淀法:其原理是PEG与蛋白质混合,随着浓度的升高,蛋白质的溶解度下降,分子量大的蛋白质首先被沉淀出来。这项方法有一些缺点,如M-PRL测定不精确,低浓度的活性PRL(mono-PRL及big-PRL)被共沉淀[7]。CHEN等[8]研究证明使用25%PEG沉淀稀释5倍后的血清样本,可以有效地降低M-PRL的浓度,提高PRL的回收率。为了提高对更小分子活性PRL的沉淀效率,本研究分别使用25%PEG沉淀法及25%PEG沉淀稀释5倍后的血清样本2种方法检测M-PRL,分析比较2种方法对真性高泌乳素血症的检出率有无差异。
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84例高泌乳素血症中有15例MP、69例真性高泌乳素血症。当使用血清稀释PEG沉淀法时,真泌组和巨泌组的PRL回收率分别是116.0%和63.0%, PRL回收率明显高于传统的PEG沉淀法(P < 0.05和P < 0.01)(见表 1~2)。
分组 n 沉淀前PRL水平/(ng/mL) 沉淀后PRL水平/(ng/mL) PRL回收率/% 血清稀释PEG沉淀法 15 41.74(31.34~179.06) 2.68(1.32~11.3) 63.0(31~90) PEG沉淀法 15 41.74(31.34~179.06) 8.61(3.31~42.7) 42.0(19~120) u — — — 2.01 P — — — < 0.05 表 1 MP组血清稀释PEG沉淀法和PEG沉淀法对PRL回收率的比较
分组 n 沉淀前PRL水平/(ng/mL) 沉淀后PRL水平/(ng/mL) PRL回收率/% 血清稀释PEG沉淀法 69 68.26(30.0~200.0) 7.59(2.78~150) 116(67~181) PEG沉淀法 69 68.26(30.0~200.0) 34.7(12.1~150) 101(56~170) u — — — 3.29 P — — — < 0.01 表 2 真性高泌乳素血症组血清稀释PEG沉淀法和PEG沉淀法对PRL回收率的比较
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84例高泌乳素血症中, 血清稀释PEG沉淀法对真性高泌乳素血症检出率为94.05%(79/84),高于PEG沉淀法的检出率84.52%(71/84)(χ2=3.98,P < 0.05)。69例有症状的真性高泌乳素血症病人(月经紊乱33例,不孕不育3例,更年期7例,颅内占位24例,溢乳2例),血清稀释PEG法检出率为97.1%(67/69),高于PEG沉淀法的检出率87.0%(60/69)(χ2=4.84,P < 0.05)。绘制ROC曲线,发现血清稀释PEG沉淀法和PEG沉淀法对MP的诊断均有一定的价值(AUC:0.932~0.939)(见表 3)。
方法 AUC 95%CI SE Sig 敏感度(真阳性/真阳性+假阴性)/% 特异性(真阴性/真阴性+假阳性)/% 血清稀释PEG沉淀法 0.939 0.851~1.0 0.045 0.000 97.1(67/67+2) 60.0(15/15+10) PEG沉淀法 0.932 0.828~1.0 0.053 0.000 87.0(60/60+9) 57.7(15/15+11) 表 3 血清稀释PEG沉淀法和PEG沉淀法对MP的诊断价值
高泌乳素血症中巨泌乳素筛查方法的研究
Study on the screening method of macroprolactin in hyperprolactinemia
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摘要:
目的探讨高泌乳素血症中巨泌乳素(M-PRL)对泌乳素(PRL)检测的干扰及应用血清稀释聚乙二醇(PEG)沉淀法筛查M-PRL血症(MP)的可行性。 方法收集84例PRL>30.0 ng/mL病人血清标本,分别使用25%PEG沉淀法及25%PEG沉淀5倍稀释后的血清标本法测定高泌乳素血症病人的PRL水平,以回收率 < 50%为判断MP的临界值。采用ROC曲线评价血清稀释PEG沉淀法和PEG沉淀法对MP的诊断价值。 结果使用25%PEG沉淀5倍稀释后的血清标本法对真泌组和巨泌组的PRL回收率分别是116.0%和63.0%,分别高于传统的PEG沉淀法中PRL的回收率的42.0%和101.0%(P < 0.05和P < 0.01);且血清稀释PEG沉淀法对真性高泌乳素血症检出率98.53%,高于PEG沉淀法的检出率88.23%(P < 0.05)。血清稀释PEG沉淀法和PEG沉淀法诊断MP的ROC曲线下面积分别为0.939 (0.851~1.0)和0.932(0.828~1.0)。 结论采用25% PEG沉淀5倍稀释后的血清标本法可以增加PRL的回收率,提高真性高泌乳素血症的检出率。 Abstract:ObjectiveTo explore the effects of macroprolactin on the detection of prolactin(PRL), and the feasibility of the serum dilution polyethylene glycol(PEG) precipitation method in the screening of hyperprolactinemia(MP). MethodsThe PRL levels in blood samples of 84 patients with serum PRL level >30.0 ng/mL were detected using the 5-fold dilution 25% PEG and PEG precipitation method.The recovery rate of PRL less than 50% was used as the standard for MP screening.The value of 25% PEG and 5-fold dilution 25% PEG in the diagnosis of MP were evaluated using ROC curve. ResultsThe recovery rates of PRL in the eutrophic and hypertrophic groups were 116.0% and 63.0% using 5-fold dilution PEG precipitation method, and which was higher than those in traditional PEG precipitation method(42.0% and 101.0%), respectively(P < 0.05 and P < 0.01).The detection rate of dilution PEG precipitation method in genuine MP was 98.53%, which was higher than that of PEG precipitation method(88.23%)(P < 0.05).The area under the ROC curve of dilution PEG and PEG precipitation methods in diagnosing MP were 0.939(0.851 to 1.0) and 0.932(0.828 to 1.0), respectively. ConclusionsThe 5-fold dilution PEG precipitation method can increase the recovery rate of PRL and detection rate of genuine MP. -
Key words:
- hyperprolactinemia /
- macroprolactin /
- macroprolactinemia /
- prolactin /
- polyethylene glycol
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表 1 MP组血清稀释PEG沉淀法和PEG沉淀法对PRL回收率的比较
分组 n 沉淀前PRL水平/(ng/mL) 沉淀后PRL水平/(ng/mL) PRL回收率/% 血清稀释PEG沉淀法 15 41.74(31.34~179.06) 2.68(1.32~11.3) 63.0(31~90) PEG沉淀法 15 41.74(31.34~179.06) 8.61(3.31~42.7) 42.0(19~120) u — — — 2.01 P — — — < 0.05 表 2 真性高泌乳素血症组血清稀释PEG沉淀法和PEG沉淀法对PRL回收率的比较
分组 n 沉淀前PRL水平/(ng/mL) 沉淀后PRL水平/(ng/mL) PRL回收率/% 血清稀释PEG沉淀法 69 68.26(30.0~200.0) 7.59(2.78~150) 116(67~181) PEG沉淀法 69 68.26(30.0~200.0) 34.7(12.1~150) 101(56~170) u — — — 3.29 P — — — < 0.01 表 3 血清稀释PEG沉淀法和PEG沉淀法对MP的诊断价值
方法 AUC 95%CI SE Sig 敏感度(真阳性/真阳性+假阴性)/% 特异性(真阴性/真阴性+假阳性)/% 血清稀释PEG沉淀法 0.939 0.851~1.0 0.045 0.000 97.1(67/67+2) 60.0(15/15+10) PEG沉淀法 0.932 0.828~1.0 0.053 0.000 87.0(60/60+9) 57.7(15/15+11) -
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