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垂体功能减退症的实验室评估陷阱。

Pitfalls in the lab assessment of hypopituitarism.

机构信息

Medizinische Klinik und Poliklinik IV, LMU Klinikum, München, Germany.

Deggendorf Institute of Technology, Deggendorf, Germany.

出版信息

Rev Endocr Metab Disord. 2024 Jun;25(3):457-465. doi: 10.1007/s11154-024-09881-1. Epub 2024 Apr 13.

DOI:10.1007/s11154-024-09881-1
PMID:38609701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11162359/
Abstract

The diagnostic approach to hypopituitarism involves many disciplines. Clinical symptoms rarely are specific. Imaging techniques are helpful but cannot prove the specific functional defects. Therefore, the definitive diagnosis of pituitary insufficiency is largely based on laboratory tests. However, also laboratory methods come with inherent limitations, and it is essential for the clinician to know and recognize typical pitfalls. Most factors potentially impairing the quality of hormone measurements are introduced in the preanalytical phase, i.e. before the hormones are measured by the laboratory. For example, the timing of blood drawing with respect to circadian rhythm, stress, and medication can have an influence on hormone concentrations. During the actual analysis of the hormones, cross-reactions with molecules present in the sample presenting the same or similar epitopes than the intended analyte may affect immunoassays. Interference can also come from heterophilic or human anti-animal antibodies. Unexpected problems can also be due to popular nutritional supplements which interfere with the measurement procedures. An important example in this respect is the interference from biotin. It became only clinically visible when the use of this vitamin became popular among patients. The extreme serum concentrations reached when patients take it as a supplement can lead to incorrect measurements in immunoassays employing the biotin-streptavidin system. To some extent, hormone analyses using liquid chromatography mass spectrometry (LCMS) can overcome problems, although availability and cost-effectiveness of this method still imposes restrictions. In the post-analytical phase, appropriateness of reference intervals and cut-offs with respect to the specific analytical method used is of outmost importance. Furthermore, for interpretation, additional biological and pharmacological factors like BMI, age and concomitant diseases must be considered to avoid misinterpretation of the measured concentrations. It is important for the clinician and the laboratory to recognize when one or more laboratory values do not match the clinical picture. In an interdisciplinary approach, the search for the underlying cause should be initiated.

摘要

垂体功能减退症的诊断方法涉及多个学科。临床症状通常不具有特异性。影像学技术有一定帮助,但无法证明具体的功能缺陷。因此,垂体功能减退症的明确诊断主要基于实验室检查。然而,实验室方法本身也存在局限性,临床医生了解并识别典型陷阱至关重要。大多数可能影响激素测量质量的因素都出现在分析前阶段,即在实验室测量激素之前。例如,采血时间与昼夜节律、应激和药物的关系会影响激素浓度。在对激素进行实际分析时,与样本中存在的与目标分析物具有相同或相似表位的分子发生交叉反应可能会影响免疫测定。干扰也可能来自异嗜性或人抗动物抗体。由于与测量程序相互干扰的常用营养补充剂,也会出现意想不到的问题。在这方面,一个重要的例子是生物素的干扰。当这种维生素在患者中广泛使用时,它才在临床上显现出来。当患者作为补充剂服用时,其血清浓度达到极端水平,会导致使用生物素-链霉亲和素系统的免疫测定出现错误测量。在某种程度上,使用液相色谱-质谱法(LCMS)进行激素分析可以克服这些问题,尽管这种方法的可用性和成本效益仍然存在限制。在分析后阶段,针对所使用的特定分析方法,参考区间和截止值的适当性非常重要。此外,为了进行解释,还必须考虑 BMI、年龄和伴随疾病等其他生物学和药理学因素,以避免对测量浓度的误解。临床医生和实验室都必须认识到何时一个或多个实验室值与临床情况不匹配。在跨学科方法中,应启动寻找潜在病因的工作。