Laboratory Testing for Endocrine Abnormalities

内分泌异常的发生，或者？自我定义？疾病或与其他疾病的组合。越来越多的？非内分泌？还发现疾病与内分泌异常有关。最佳使用有效的实验室检查和正确诊断内分泌疾病或内分泌成分？非内分泌？疾病显然在医学和经济上都很重要。甲状腺疾病是最常见的内分泌异常，而其他内分泌疾病如嗜铬细胞瘤相对少见。虽然嗜铬细胞瘤是一种罕见的高血压的原因，个案研究结果需要筛选大量的病人。近四分之一的美国人患有高血压，但这些患者中只有0.1-0.5%会被发现患有嗜铬细胞瘤。然而，诊断这些患者是重要的，因为约90%可以通过手术治愈，而如果疾病未被识别和/或未得到治疗，后果可能是灾难性的。尽管临床实验室越来越多地使用儿茶酚胺和代谢物测量来诊断嗜铬细胞瘤（以及各种其他病症/疾病），但关于最佳标本采集的信息仍然有限。我们比较了两种最常用的抗凝剂对儿茶酚胺和代谢物的测量。从健康受试者和接受嗜铬细胞瘤评价的患者中获得肝素和EDTA抗凝静脉血（未添加抗氧化剂）。在采集后1至3小时内将血浆与细胞分离。血浆样本在-70 ℃下冷冻1天至14个月，直至检测。如前所述，通过高效液相色谱法（HPLC）测定血浆儿茶酚（L-多巴、多巴胺、去甲肾上腺素、肾上腺素、3，4-二羟基苯乙酸[DOPAC]、3，4-二羟基苯乙二醇[DHPG]）和游离（未结合）甲氧基酪胺和变肾上腺素（去甲变肾上腺素、变肾上腺素）。尽管差异并不总是达到统计学显著性（配对t检验），但EDTA血浆中各种儿茶酚胺和儿茶酚胺代谢物的浓度均低于肝素血浆。相比之下，EDTA血浆中游离甲氧酪胺和游离变肾上腺素的浓度往往高于肝素血浆，但差异无统计学显著性。我们的研究结果表明，抗凝剂（肝素与EDTA）的选择对血浆儿茶酚胺测量具有临床重要影响，也可能影响游离甲氧酪胺和变肾上腺素的测量。我们将数据解释为表明血浆儿茶酚在EDTA血液中的稳定性低于肝素化血液。O-甲基化代谢物的相互差异表明涉及红细胞酶儿茶酚-O-甲基转移酶（COMT）。我们观察到的实际影响是双重的。首先，由于EDTA似乎是最广泛使用的抗凝血剂，用于测量儿茶酚和变肾上腺素，实验室可能需要重新评估其用于标本采集。其次，不同实验室之间观察到的这些分析物的参考区间差异可能至少部分归因于抗凝剂的选择，这需要被认识到以正确解释检测结果。 在一项合作研究中，我们发现血浆游离肾上腺素的测量不仅提供了有关嗜铬细胞瘤可能存在或不存在的信息，而且当肿瘤存在时，还可以帮助预测肿瘤的大小和位置。这些额外的信息可能有助于肿瘤定位过程中的临床决策。虽然血浆游离normetanetamine和metanetamine的测量提供了诊断嗜铬细胞瘤的敏感测试，这些测试可能无法检测主要产生多巴胺的肿瘤。这种肿瘤是非常罕见的，通常被发现为肾上腺外副神经节瘤。在一项合作研究中，我们发现，血浆游离甲氧酪胺的测量，除了normetanelamine和metanelamine，是不太可能提高诊断嗜铬细胞瘤的高血压患者的症状，儿茶酚胺过量，但可能是有用的，在选定的患者确定的肿瘤，主要产生多巴胺。

Endocrine abnormalities occur either as ?self-defined? disorders or in combination with other diseases. An ever-increasing number of ?non-endocrine? diseases also are found to be associated with endocrine abnormalities. Optimal use of valid laboratory tests and correct diagnosis of endocrine diseases or the endocrine components of ?non-endocrine? diseases obviously are important both medically and economically. Thyroid diseases represent the most common endocrine abnormalities, while other endocrine diseases such as pheochromocytoma are relatively uncommon. Although pheochromocytoma is a rare cause of hypertension, case findings require screening of a large numbers of patients. Nearly one in four Americans has hypertension, but only 0.1-0.5% of these patients will be found to have pheochromocytoma. Nevertheless, diagnosing these patients is important since ~90% can be cured with surgery, while the consequences can be catastrophic for the patient if the disease goes unrecognized and/or untreated. Despite the increasing use of catecholamine and metanephrine measurements in clinical laboratories for the diagnosis of pheochromocytoma (and for a variety of other conditions/diseases), information regarding optimal specimen collection remains limited. We compared the two most commonly used anticoagulants on catecholamine and metanephrine measurements. Heparin- and EDTA-anticoagulated venous blood (without added antioxidant[s]) was obtained from healthy subjects and patients who were evaluated for pheochromocytoma. Plasma was separated from cells within 1 to 3 hours after collection. Plasma specimens were frozen from 1 day to 14 months at -70 Celsius degrees until testing. Plasma catechols (L-dopa, dopamine, norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid [DOPAC], 3,4-dihydroxyphenylglycol [DHPG]) and free (unconjugated) methoxytyramine and metanephrines (normetanephrine, metanephrine) were measured by high-performance liquid chromatography (HPLC) methods as described previously. Although the differences did not always reach statistical significance (paired t-test), the concentrations of various catecholamines and catecholamine metabolites were all lower in EDTA plasma than heparin plasma. In contrast, the concentrations of free methoxytyramine and free metanephrines tended to be higher in EDTA than heparin plasma, but the differences were not statistically significant. Our findings show that the choice of anticoagulant (heparin vs. EDTA) has clinically important effects on plasma catecholamine measurements and also may affect measurements of free methoxytyramine and metanephrines. We interpret the data as indicating that plasma catechols are less stable in EDTA blood than heparinized blood. The reciprocal differences in O-methylated metabolites suggest involvement of the red blood cell enzyme catechol-O-methyltransferase (COMT). The practical implications of our observations are two-fold. First, since EDTA appears to be the most widely used anticoagulant for the measurements of catechols and metanephrines, laboratories may need to re-assess its use for specimen collection. Second, observed differences in reference intervals for these analytes between various laboratories may, at least in part, attributable to the choice of anticoagulants and this needs to be recognized for correct interpretation of the test results. In a collaborative study, we showed that measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures. While measurements of plasma-free normetanephrine and metanephrine provide a sensitive test for diagnosis of pheochromocytoma, these tests may fail to detect tumors that produce predominantly dopamine. Such tumors are extremely rare, usually found as extraadrenal paragangliomas. In a collaborative study we showed that measurements of plasma free methoxytyramine, in addition to normetanephrine and metanephrine, are unlikely to improve diagnosis of pheochromocytomas in hypertensive patients with symptoms of catecholamine excess but may be useful in selected patients for identification of tumors that produce predominantly dopamine.