用聚乙二醇沉淀法筛查高泌乳素血症的应用评价

目的探讨用聚乙二醇（PEG）沉淀法去除假性高泌乳素（PRL）血症的临床应用评价。方法测定232例高值PRL患者及52名正常体检者血清PRL,血清经PEG沉淀后再次测定其PRL,同时用缓冲液沉淀做对照,并对二者结果进行比较。结果高值PRL组中巨PRL检出率为25．4％,正常对照组中巨PRL的检出率为0．0％,2组差异有统计学意义（P〈0．01）。单体PRL组PEG处理前后血清PRL差异无统计学意义（P〉0．05）,而巨PRL组和可疑巨PRL组PEG处理前后PRL差异有统计学意义（P〈0．01）。3组经缓冲液处理前后PRL差异无统计学意义（P〉0．05）。结论高值PRL部分是假性升高,用PEG沉淀法筛查高值PRL对提高临床诊断的准确性有一定的价值,能减少对高PRL血症的误诊。     

聚乙二醇沉淀法与凝胶色谱层析法检测巨泌乳素的相关性研究

目的探讨聚乙二醇（PEG）沉淀法检测巨泌乳素（MPRL）方法的可行性。方法将26例高泌乳素血症（HPRL）患者按临床表现和影像学资料分为真性HPRL组（简称真泌组）11例及MPRL血症组（简称巨泌组）15例。采用凝胶色谱层析（GFC）法分离泌乳素（PRL）各组分,检测各组分PRL浓度,同时将所有标本进行PEG沉淀,检测处理后单体PRL浓度,并与GFC法单体PRL检测结果进行相关性分析。结果巨泌组与真泌组的PRL层析谱不同,真泌组以单体PRL为主,而巨泌组以巨PRL为主。真泌组与巨泌组血清处理前总PRL浓度差异无统计学意义（P〉0．05）,而处理后真泌组明显高于巨泌组（P〈0．05）。PEG沉淀法与GFC法检测真泌组与巨泌组单体PRL浓度差异无统计学意义（P〉0．05）,且相关性良好[相关系数（r）=0．844,P〈0．05]。结论PEG沉淀法检测MPRL结果与GFC法有良好的相关性,且经济、简便、易行,可作为临床常规筛查方法。     

高泌乳素血症中泌乳素成分分析及其临床价值

目的探讨巨泌乳素测定在高泌乳素血症诊断中的价值。方法对160例高泌乳素血症患者和110名健康体检者的皿清进行泌乳素值测定,然后用聚乙二醇（PEG）处理,再次测定其泌乳素水平,根据其回收率来区分真高泌乳素血症和巨泌乳素血症。结果高泌乳素血症患者中巨泌乳素血症检出率[22．50％（36／160）]明显高于健康体检者中巨泌乳素血症的检出率[0．91％（1／110）]（P〈0．01）。真高泌乳素患者经溴隐亭治疗后,泌乳素水平有所下降,临床症状有好转。结论用PEG沉淀法区分真高泌乳素血症和巨泌乳素血症对其治疗有重要意义。     

巨泌乳素筛查在高泌乳素血症诊断中的临床意义

目的比较不同类型高泌乳素血症(HPRL)的激素水平及临床表现,探讨筛查巨泌乳素在HPRL诊断中的意义。方法将2011年5月至2013年5月就诊的HPRL女性患者124例纳入HPRL组,另选取同期体检健康的育龄妇女45例纳入健康对照组;使用罗氏E170全自动电化学发光免疫分析仪测定124例HPRL患者血浆卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)及经聚乙二醇(PEG)6000沉淀前后的泌乳素水平,并根据泌乳素回收率分成巨泌乳素、单泌乳素及可疑泌乳素型,记录相关临床症状;同时检测健康对照组的泌乳素水平。结果 HPRL患者巨泌乳素检出率(33.1%)高于健康对照组,组间比较差异有统计学意义(P0.05);经PEG沉淀前后,巨泌乳素型HPRL血浆泌乳素水平比较差异有统计学意义(P0.05);经PEG沉淀前,不同类型HPRL血浆FSH、LH、E2水平及LH/FSH比值比较,差异均无统计学意义(P0.05);巨泌乳素型HPRL常见临床症状的发生率为44%,单体泌乳素型为81%,组间比较差异有统计学意义(P0.05)。结论通过巨泌乳素筛查可区分HPRL的类型,指导HPRL临床用药并避免不必要的检查和误诊。     

高泌乳素患者不同时间段泌乳素水平研究

目的 探讨高泌乳素血症患者泌乳素水平在不同时间段的变化。方法 使用电化学发光法、罗氏E170全自动免疫分析仪测定124例高泌乳素(PRL>880 uIU/ml),女性患者在7:30AM,10:00AM及4:00PM不同时间段血浆泌乳素(PRL)水平,并根据经聚乙二醇(PEG)6000沉淀巨泌乳素后的PRL回收率分成巨泌乳素组(回收率≤40%)、单泌乳素组(回收率>60%)、可疑泌乳素组(40%<回收率≤60%),同时检测45例正常对照组的PRL水平。结果 高泌乳素组巨泌乳素阳性率(33.1%)与正常对照组中巨泌乳素阳性率(0.0%)比较,差异有统计学意义(χ2=17.886 7,P<0.05),巨泌乳素组及单体泌乳素组经PEG处理前在10:00AM时间段的泌乳素浓度(1160±714 uIU/ml,885±801 uIU/ml)与7:30AM时间段的泌乳素浓度(1 521±914 uIU/ml,1 497±845 uIU/ml)差异均有统计学意义(t=1.993,4.46,P<0.05),巨泌乳素组及单体泌乳素组经PEG处理后在10:00AM时间段的泌乳素浓度(316±231 uIU/ml,766±611 uIU/ml)与7:30AM时间段的泌乳素浓度(488±394 uIU/ml,1235±912 uIU/ml)差异均有统计学意义(t=2.411 4,3.625 2,P<0.05),单泌乳素组4:00PM时间段处理前的泌乳素浓度(1 033±911 uIU/ml)与7:30AM时间段处理前的泌乳素浓度(1 497±845 uIU/ml)差异也有统计学意义(t=3.168 6,P<0.05)。结论 不同时间段泌乳素水平有变化,确定正确的采血时间,有助于临床对高泌乳素血症的诊断。     

高泌乳素血症患者筛查巨泌乳素的临床意义

目的探讨高泌乳素血症患者中巨泌乳素（M-PRL）血症的检出率,比较M-PRL血症患者和高单体泌乳素血症患者的临床表现和激素水平。方法使用Architect i2000免疫分析仪测定185例泌乳素（PRL）超过35μg/L的女性患者血清PRL、黄体生成素（LH）、卵泡刺激素（FSH）、雌二醇（E2）和经聚乙二醇（PEG）6000沉淀后的PRL水平。记录临床症状用作回顾性分析。结果 M-PRL检出率为21%,月经过少、闭经和溢乳等症状在高单体泌乳素血症患者中的出现率（88%）高于M-PRL血症患者（47%）（P〈0.05）。M-PRL血症患者E2、LH水平和LH/FSH比值明显高于高单体泌乳素血症患者（P〈0.05）。结论 M-PRL在高泌乳素血症患者中经常发生,但仅部分患者有相关症状,建议所有高泌乳素血症患者筛查M-PRL。     

用聚乙二醇沉淀法筛检巨催乳素血症及临床意义分析

目的探讨聚乙二醇沉淀法筛测巨催乳素血症的临床意义。方法用聚乙二醇沉淀法,对260例高催乳素血症患者血清进行小分子催乳素的回收率及LH、E2浓度测定,区分巨催乳素血症和真高催乳素血症,回顾性分析两者的临床体征。结果真高催乳素血症及巨催乳素血症在聚乙二醇处理前两组催乳素浓度无显著性差异(P>0.05);处理后两组催乳素浓度有显著性差异(P<0.05);真高催乳素血症的LH、E2浓度低于巨催乳素血症组及正常对照组;两组患者均表现月经紊乱、闭经、溢乳,但前者发生的显著高于后者。结论真高催乳素血症及巨催乳素血症临床上难于区别,用聚乙二醇沉淀法能有效区分两者,减少对真高催乳素血症的误诊。     

影响泌乳素浓度的原因分析

目的探讨影响泌乳素浓度的原因。方法用电化学发光法:(1)同时检测两个不同采血时间段所得标本的泌乳素含量;(2)检测经聚乙二醇处理前后的泌乳素含量。结果两个不同时间段的泌乳素含量间差异有统计学意义(P0.05);53例高泌乳素血清中检出含巨泌乳素有13例,含巨泌乳素的标本经聚乙二醇处理前后泌乳素含量差异有统计学意义(P0.05)。结论确定采血时间,去除巨泌乳素的干扰,有助于高泌乳素血症的判断和确诊。     

采用离心浓集法提高乙型肝炎病毒表面抗原检出率的可行性研究

目的 探讨离心浓集法预处理血清标本对提高乙型肝炎血清学标志物乙型肝炎表面抗原(HBsAg)检出率的可行性研究.方法 收集广州市内各大医院2009年52例HBsAg阳性者和疑似乙型肝炎感染者血清标本,分别用酶联免疫吸附试验(ELISA) 和化学发光免疫分析法(CLIA)测定HBsAg.再以PEG6000为沉淀剂,将标本进行高速离心浓集(30 000 r/min)25 ℃,40 min,取沉淀用TE Buffer溶解,采用上述相同方法分别进行测定,比较离心前后其HBsAg 的S/CO值与HBsAg定量值的上升情况,用SPSS统计学软件对数据进行非参数检验,分析其差别是否有统计学意义.结果 健康对照组与空白对照经高速离心处理前后的HBsAg 检测结果差异均无统计学意义(P>0.05),而疑似HBV感染组和HBV感染组患者血清经高速离心预处理后的测定结果均明显高于处理前(P<0.01).结论 离心浓集法预处理对于血清中有低水平乙型肝炎病毒颗粒的感染者有效,血清中的病毒颗粒可通过高速离心处理后得到浓缩,提高临床实验室常规诊断手段的灵敏度的范围,使隐匿型乙型肝炎的检出率有所提高.     

胰岛素抗体对电化学发光免疫分析法测定血清胰岛素的影响

目的探讨胰岛素抗体(IA)对电化学发光免疫分析法(ECLIA)检测胰岛素的影响。方法放射免疫法检测糖尿病患者血清IA,IA结合率<5%组10例,IA结合率≥5%组53例。聚乙二醇(PEG)沉淀法去除IA,Roche E lecsys 2010测定胰岛素浓度。结果IA结合率<5%组和IA结合率5%~10%组PEG处理前后的胰岛素浓度、游离胰岛素/直接胰岛素比值、胰岛素浓度改变值差异均无统计学意义(P>0.05)。IA结合率10%~20%、20%~30%、>30%组PEG处理前后的胰岛素浓度、游离胰岛素/直接胰岛素比值、胰岛素浓度改变值差异有统计学意义(P<0.05)。IA结合率>10%时,IA结合率与游离胰岛素/直接胰岛素比值呈负相关(r=-0.729,P=0.000),与胰岛素浓度的改变值呈正相关(r=0.821,P=0.000)。结论IA结合率≤10%时,IA对ECLIA测定血清胰岛素浓度没有影响。IA结合率>10%时,IA使ECLIA测定胰岛素结果假性升高。     

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay

OBJECTIVE: To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. DESIGN AND METHODS: Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p<0.05) normalisation of PRL following PEG. RESULTS: PRL recovery was similar in volunteer and hyperprolactinemic samples (mean+/-SD 101+/-13% and 101+/-19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. CONCLUSIONS: Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived.     

Free prolactin determinations in hyperprolactinemic men with suspicion of macroprolactinemia.

BACKGROUND: The Elecsys prolactin (PRL) assay reacts more strongly with macroprolactin than the Centaur PRL assay. We evaluated Elecsys direct and free PRL measurements vs. Centaur direct PRL measurements, in sera with and without macroprolactin. METHODS: PRL was measured using Elecsys and Centaur direct assays and the Elecsys assay in the supernatant obtained after PEG precipitation (free PRL) in 34 sera from 34 hyperprolactinemic male subjects (Elecsys direct PRL>434 mIU/l) classified, according to the PRL recovery after PEG precipitation, as: negative, i.e. without predominant macroprolactin (recovery %>50, n=12), positive (recovery %<40, n=18) or indeterminate (n=4). RESULTS: The positive bias between Elecsys direct and Centaur PRL results was clearly influenced by the presence of macroprolactin and the mean bias between Elecsys free and Centaur prolactin values was near zero in the negative and positive groups. Among 14 patients from the positive group presenting clinical conditions possibly ascribable to hyperprolactinemia, Elecsys free and Centaur PRL levels were normal in seven and increased in five. In the negative and positive groups considered together, Elecsys free PRL agreed well with Centaur prolactin (28/30). The poor concordance observed for the indeterminate samples underlined the heterogeneity of macroprolactin. CONCLUSION: Elecsys free PRL determination can be used to reduce the marked influence of macroprolactin in this assay.     

Reactivity of macroprolactin in common automated immunoassays.

OBJECTIVES: To evaluate a simple assay for macroprolactin for use with the Bayer Immuno 1 analyzer, and to compare the reactivity of macroprolactin in commonly used automated prolactin assays. METHODS: Macroprolactin in serum was precipitated in a buffer containing 13.3% polyethylene glycol (PEG) 8000, redissolved, and assayed on the Bayer Immuno 1 for PRL. Presence of macroprolactin was confirmed in some sera by FPLC using a Pharmacia Superose 12 column, followed by prolactin assay of the fractions on the Immuno 1. Sera with and without macroprolactin were then also assayed on the Abbott AxSYM, Bayer Centaur, Beckman Access, and Roche Elecsys. RESULTS: The PEG precipitation assay is simple and reproducible (CVs < 15%), and we established a normal range of < 20% precipitation of total PRL by PEG. The assay correlates well with the amount of macroprolactin separated by FPLC as a peak with a MW of approximately 180 kDa. Macroprolactin showed the following cross-reactivities in commonly used PRL assays: Roche Elecsys > Bayer Immuno 1 > Abbott AxSYM > Bayer Centaur > Beckman Access, with the Centaur showing more variability than other assays. CONCLUSION: Macroprolactin can be easily quantitated using the Immuno 1 PRL assay after PEG precipitation. It cross-reacts to different degrees with common prolactin assays, and is a major source of variability between them.     

Rapid detection of macroprolactin in the form of prolactin-immunoglobulin G complexes by immunoprecipitation with anti-human IgG-agarose.

Immunoprecipitation with anti-human immunoglobulin G-agarose was evaluated for the detection of prolactin-immunoglobulin G (PRL-IgG) complexes in macroprolactinemic samples from hyperprolactinemic patients (prolactin measured using the automated Elecsys PRL assay; Roche Diagnostics, Mannheim, Germany). Using the polyethylene glycol (PEG) precipitation test on serum samples with PRL above 1000 mIU/l, we detected macroprolactin in 38 out of 175 samples with a recovery below 50%. Gel filtration chromatography on a subset of hyperprolactinemic samples confirmed that macroprolactin was the predominant immunoreactive form of PRL in samples which showed a recovery < or = 50%. In 37 out of 38 samples containing macroprolactin, immunoprecipitation with anti-human IgG (anti-hIgG)-agarose revealed a higher PRL-binding (19.1-91.3%) than in the sera containing monomeric PRL (< 10%). In conclusion, we found that PEG precipitation detected macroprolactin in 21.7% of samples with elevated PRL levels as measured by the Elecsys PRL assay, and that in the vast majority of these samples the presence of PRL-IgG complexes could be demonstrated by immunoprecipitation with anti-hIgG-agarose. In view of the high prevalence of PRL-IgG complexes in hyperprolactinemic patients and the simplicity of the test, immunoprecipitation with anti-hIgG-agarose might play a role in the routine laboratory handling of hyperprolactinemic samples, especially with regards to PRL assays where PEG causes interference.     

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG). We compared the reactivities with macroprolactin of the PRL II, the PRL I and seven other PRL assays. The PRL II assay reacted less strongly than the PRL I assay and similarly to the ADVIA Centaur assay with macroprolactin. PEG precipitation can be used with the PRL II assay to estimate the concentration of monomeric PRL.     

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG). We compared the reactivities with macroprolactin of the PRL II, the PRL I and seven other PRL assays. The PRL II assay reacted less strongly than the PRL I assay and similarly to the ADVIA Centaur assay with macroprolactin. PEG precipitation can be used with the PRL II assay to estimate the concentration of monomeric PRL.     

Relationship between high prolactine levels and migraine attacks in patients with microprolactinoma

The pathophysiology of pituitary-associated headache is unknown, although structural and functional features of the tumour are proposed mechanisms. The objective of this study was to evaluate whether headache in a population with pituitary micro-adenomas was related to hyperprolactinemia. We recruited 29 patients with microprolactinoma and headache: 16 with migraine (group A) and 13 with tension-type-headache (group B). The prolactin (PRL) levels measured during attacks of headache were significantly higher in nine patients (56%) of group A and in one patient (8%) of group B. In four of the nine patients of group A, PRL increased after thyrotropin-releasing-hormone (TRH) test and induced severe attacks. After dopamine-agonist (DA) treatment, the headache improved in seven (44%) patients of the group A and in two (15%) patients of the group B. Three of the four patients in whom the TRH-test induced headache attacks, improved after DA treatment. We suggest that hyperprolactinemia may contribute to development of pain in migraine subgroups and further TRH-test could be used to predict which patients could benefit by DA therapy.