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高剂量生物素治疗导致虚假的生化内分泌谱:验证一种简单的方法来克服生物素干扰。

High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference.

机构信息

Service des explorations fonctionnelles, G.H. Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris cedex 15.

Service des explorations fonctionnelles, G.H. Necker Enfants Malades, Paris.

出版信息

Clin Chem Lab Med. 2017 May 1;55(6):817-825. doi: 10.1515/cclm-2016-1183.

DOI:10.1515/cclm-2016-1183
PMID:28222020
Abstract

BACKGROUND

High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various endocrine disorders. We aimed at exploring this interference, to be able to remove biotin and avoid misleading results.

METHODS

We measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), parathyroid homrone (PTH), 25-hydroxyvitamin D (25OHD), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, C-peptide, cortisol (Roche Diagnostics assays), biotin and its main metabolites (liquid chromatography tandem mass spectrometry) in 23 plasmas from MS patients and healthy volunteers receiving high-dose biotin, and in 39 biotin-unsupplemented patients, before and after a simple procedure (designated N5) designed to remove biotin by means of streptavidin-coated microparticles. We also assayed fT4, TSH and PTH in the 23 high-biotin plasmas using assays not employing streptavidin-biotin binding.

RESULTS

The biotin concentration ranged from 31.7 to 1160 µg/L in the 23 high-biotin plasmas samples. After the N5 protocol, the biotin concentration was below the detection limit in all but two samples (8.3 and 27.6 μg/L). Most hormones results were abnormal, but normalized after N5. All results with the alternative methods were normal except two slight PTH elevations. In the 39 biotin-unsupplemented patients, the N5 protocol did not affect the results for any of the hormones, apart from an 8.4% decrease in PTH.

CONCLUSIONS

We confirm that most streptavidin-biotin hormone immunoassays are affected by high biotin concentrations, leading to a risk of misdiagnosis. Our simple neutralization method efficiently suppresses biotin interference.

摘要

背景

高剂量生物素治疗对进展性多发性硬化症(MS)有益,预计会有大量患者采用这种治疗方法。生物素治疗会导致许多利用链霉亲和素-生物素捕获技术的免疫分析出现分析干扰,得出的结果会出现偏差,类似于各种内分泌紊乱。我们旨在探索这种干扰,以便能够去除生物素并避免误导性的结果。

方法

我们测量了 23 例接受高剂量生物素治疗的 MS 患者和健康志愿者的 23 份血浆中的游离三碘甲状腺原氨酸(fT3)、游离甲状腺素(fT4)、促甲状腺激素(TSH)、甲状旁腺激素(PTH)、25-羟维生素 D(25OHD)、卵泡刺激素(FSH)、黄体生成素(LH)、催乳素、C 肽、皮质醇(罗氏诊断检测)、生物素及其主要代谢物(液相色谱串联质谱法),以及 39 例未补充生物素的患者在接受一种简单的(命名为 N5)去除生物素的方案(即用链霉亲和素包被的微粒子)前后的上述指标。我们还使用不采用链霉亲和素-生物素结合的检测方法测定了这 23 例高生物素血浆中的 fT4、TSH 和 PTH。

结果

在 23 例高生物素血浆样本中,生物素浓度范围为 31.7 至 1160μg/L。N5 方案后,除了两个样本(8.3 和 27.6μg/L)外,所有样本的生物素浓度均低于检测下限。大多数激素结果异常,但 N5 后均恢复正常。除了两项轻微的 PTH 升高外,所有替代方法的结果均正常。在 39 例未补充生物素的患者中,除了 PTH 降低 8.4%外,N5 方案对任何激素的结果均无影响。

结论

我们证实,大多数链霉亲和素-生物素激素免疫分析都会受到高生物素浓度的影响,导致误诊风险增加。我们的简单中和方法能有效地抑制生物素干扰。

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