血浆嗜铬粒蛋白A对多种神经内分泌肿瘤的诊断价值

目的 探讨血浆嗜铬粒蛋白A(CgA)对神经内分泌肿瘤的诊断价值,同时评价血浆CgA对胃肠胰腺内分泌肿瘤的诊断效力,初步探讨血浆CgA对胃肠胰腺内分泌肿瘤预后的监测作用.方法 应用酶联免疫试剂盒检测56例胃肠胰腺内分泌肿瘤、52例嗜铬细胞瘤和7例小细胞肺癌的血浆CgA浓度,同时以52例健康体检者作为对照,计算血浆CgA诊...     

嗜铬细胞瘤诊断与定位的进展

血浆儿茶酚胺的测定对嗜铬细胞瘤诊断和定位是一种最敏感和最可靠的方法。其诊断标准：静息卧位血浆去甲肾上腺素＞１１．８２ｐｍｏｌ／ｍｌ及／或肾上腺素＞５．４６ｐｍｏｌ／ｍｌ。肿瘤主要以持续弥散方式释放儿茶酚胺，根据其释放量，可分为多分泌型与少或不分泌型。血浆儿茶酚胺浓度取决于肿瘤分泌会，而与肿瘤大小和儿茶酚胺总含量无关。腔静脉分段取血定位肿瘤阳性率为９７％。分别测定血浆去甲肾上腺素和肾上腺素有助于肿瘤位置的判断。对极少数病例，血浆儿茶酚胺正常不能完全排除嗜铬细胞瘤。因生理病理应激使血浆儿茶酚胺升高时，也不要误诊为嗜铬细胞瘤。我国在这方面研究已达到国际先进水平。     

胰腺神经内分泌肿瘤

胰腺神经内分泌肿瘤（PNET）临床少见，表现为功能性和无功能性，来源于胰岛细胞，又称为胰岛细胞瘤（ICTs）。PNET是胰腺肿瘤很重要的一种类型，约占临床诊断胰腺肿瘤的2％-4％，包括单发、多发，良性、恶性等多种类型，其中10％～20％伴有多发内分泌肿瘤（MEN）。     

生长抑素受体显像在内分泌临床的应用

许多内分泌肿瘤和组织都有高密度生长抑素受体（SSR）表达，目前生长抑素受体显像（SRS）已广泛应用于临床。研究证实SRS对功能性或无功能性胰腺内分泌肿瘤、类癌及副神经节瘤等具有明显显像价值；对垂体腺瘤、嗜铬细胞瘤及甲状腺疾病也可能具有一定显像价值。此外SRS还可以作为类癌和垂体瘤对生长抑素治疗反应的预测指标。研究证实放射性标记的SSR靶向放射治疗是神经内分泌肿瘤有效的姑息治疗方法。随着对SRS和SSR靶向放射治疗的认识不断加深，将为内分泌肿瘤的诊治开拓广阔前景。     

腔静脉血浆儿茶酚胺对嗜铬细胞瘤的定位

腔静脉血浆儿茶酚胺对嗜铬细胞瘤的定位金律，刘力生，王蕾礼，郑德裕应用高效液相色谱电化学检测法（ＨＰＬＣ－ＥＣ）测定腔静脉血浆儿茶酚胺（ＣＡ）对嗜铬细胞瘤定位，并探索此法对肿瘤定位的标准。一、对象和方法：经手术、病理与肿瘤ＣＡ检查证实的嗜铬细胞瘤患者９...     

肾上腺外嗜铬细胞瘤25例临床分析

目的 分析肾上腺外嗜铬细胞瘤的发病情况，病理特征及诊断方法，探讨治疗措施。方法 通过对81例经手术与病理证实的嗜铬细胞瘤进行回顾性分析。结果 81例嗜铬细胞瘤患者中，经手术与病理证实的肾上腺外嗜铬细胞瘤25例，占同期收治嗜铬细胞瘤的30．9％。病人的临床表现除特殊部位肿瘤外与肾上腺髓质嗜铬细胞瘤相似。结论 肾上腺外嗜铬细胞瘤临床表现与生化诊断与肾上腺髓质嗜铬细胞瘤相似，其恶性者较肾上腺髓质嗜铬细胞瘤明显增多，定位诊断以^131I-MIBG为特异，治疗以手术最佳。     

胃肠神经内分泌肿瘤和胰腺神经内分泌肿瘤的区别

胃肠胰神经内分泌肿瘤（GEP-NETs）主要来源于胃肠胰系统的神经内分泌细胞,这一细胞系统和肿瘤是以表达细胞类型特异的肽激素和普通标记物（突触囊泡蛋白、铬粒素A）为特征。其特点为：临床上少见;肿瘤通常较小（〈1 cm）;生长速度较慢（数月或数年）,呈阶段性表达,可能数年无症状;通常在出现症状前即有转移,转移部位多为肝脏和骨,而此时肿瘤的体积通常〉2cm。因此这类肿瘤经常被误诊,诊断过程较复杂,不单单依靠临床,往往需要高端的实验室和扫描手段支持。而GEP-NETs中胃肠神经内分泌肿瘤（NET）和胰腺NET,两者在临床表现、诊断和治疗方面也有不同,需要临床医生重视和加以区分。     

肝嗜铬细胞瘤1例报告

正嗜铬细胞瘤是一种起源于肾上腺嗜铬细胞的神经内分泌肿瘤,它可以持续或间断分泌儿茶酚胺,包括去甲肾上腺素、多巴胺及肾上腺素。肾上腺外来源的嗜铬细胞瘤称为转移性嗜铬细胞瘤。嗜铬细胞瘤典型的临床表现有血压异常波动、心悸、头疼等,严重者可导致高血压危象,危及生命。本文报道了1例位于肝右后叶的嗜铬细胞瘤的青年患者,并讨论了临床表现、影像学表现、组织学病理和治疗方法。1病例资料     

2021年《国际内分泌代谢杂志》第2期部分文题介绍

1.关于原发性醛固酮增多症诊治的常见误区⒉.新型远程动态血糖监测系统的准确性及安全性研究3.嗜铬细胞瘤的发病机制研究进展4.原发性醛固酮增多症的发病机制研究进展5.嗜铬粒蛋白A在诊断嗜铬细胞瘤和副神经节瘤中的意义6.286例功能性胰腺神经内分泌肿瘤的临床特点及治疗7.青年及中年时期体重状态变化及最大体重减重与中老年时期高血压的关系8.肾素瘤的诊治进展——从1例肾素瘤患者谈起.     

胃肠胰神经内分泌肿瘤诊治进展

在机体经典的内分泌腺体之外，肺、胃肠道等还广泛散在地分布着许多具有内分泌作用的细胞，这些细胞不但本身含有胺，具有摄取胺前体并脱羧的能力，而且与神经细胞有许多共同的形态、生物学和功能特性，故称为神经内分泌细胞。起源于胃肠道和胰腺神经内分泌细胞的肿瘤即胃肠胰神经内分泌细胞肿瘤（GEP-NET）。这是一组罕见的、有着不同临床表现的肿瘤，其发病约占所有消化道肿瘤的2％，在这类肿瘤中最常见的是类癌，其发病率大约为2．5／10万。     

慢性心衰患者血浆尾加压素Ⅱ与嗜铬粒蛋白A的相关性

目的：探讨血浆尾加压素Ⅱ（urotensinⅡ,UⅡ）和嗜铬粒蛋白A（CgA）浓度在不同心力衰竭分级患者中的变化及其两者之间的相关性。方法：各种病因导致的慢性心力衰竭（CHF）患者41例（心力衰竭组）,按NY-HA心功能分级标准,分为心功能Ⅱ级12例,Ⅲ级14例,IV级15例,并设健康对照组20例。采用放射免疫法测定血浆UⅡ含量,酶联免疫法测定血CgA含量,并对两组指标进行相关分析。结果：①CHF患者血浆UⅡ含量较健康对照组明显降低[心功能Ⅱ级组（2.99±0.16）pg/ml：III级组（2.57±0.12）pg/ml：IV级组（2.13±0.17）pg/ml：健康对照组（5.52±0.10）pg/ml,P〈0.01];②血浆CgA含量较健康对照组明显升高[心功能Ⅱ级组（147.00±1.41）ng/ml：III级组（276.75±2.00）ng/ml：IV级组（521.47±68.21）ng/ml：健康对照组（64.21±2.75）ng/ml,P〈0.01];③Pearson相关性分析显示,血浆UⅡ和CgA存在负相关（r值为-0.809,P〈0.01）。结论：（1）在充血性心衰患者中,随心功能级别的升高,尾加压素II含量降低,嗜铬粒蛋白A含量升高;（2）血浆尾加压素Ⅱ、嗜铬粒蛋白A共同参与了心衰的发生发展,其水平是判断心力衰竭及心室重构的可靠指标。     

Plasma chromogranin A in patients with multiple endocrine neoplasia type 1.

Plasma chromogranin A (CgA) has been claimed to be a sensitive marker for neuroendocrine tumors, but its role in the early diagnosis of multiple endocrine neoplasia type 1 (MEN 1) pancreatic endocrine tumors has not been evaluated. We measured CgA in 36 patients with MEN 1, of whom 9 lacked pancreatic involvement, 20 had biochemical evidence of pancreatic endocrine tumors, and 7 displayed radiologically detectable pancreatic tumors. CgA was also analyzed in 25 patients with sporadic pancreatic endocrine tumors, 39 subjects with inflammatory bowel disease, 7 patients harboring nonendocrine pancreatic disease, and 19 healthy controls. Four of 9 of the MEN 1 patients without pancreatic involvement had elevated CgA. Furthermore, 60% with biochemically unequivocal tumors and all with a radiologically visible tumor showed elevations. All 25 patients with sporadic pancreatic endocrine tumor had increased CgA, as had 28% of patients with inflammatory bowel disease and 57% with nonendocrine pancreatic disease. Mean day to day CgA variation was 29% (range, 0-113%) in the neuroendocrine tumor patients and 21.0% (range, 0.0-47%, within reference range) among healthy controls. In summary, nonendocrine diseases may cause elevation of CgA, and its spontaneous variation can be considerable. Plasma chromogranin A is the most sensitive of the basal markers for neuroendocrine tumors, but cannot replace other established measures when screening for early pancreatic involvement in MEN 1.     

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.     

N-端心房利钠肽与N-端脑利钠肽对预测左室收缩功能障碍的价值

目的比较N-端心房利钠肽(心钠素NT-proANP)和N-端脑钠肽(NT-proBNP)对左室收缩功能障碍(LVSD)预测效率,依据二者特性确定适用范围并界定最佳下限(cut-off)值。方法入选心血管病患者380例(病例组),依据左室射血分数(LVEF)将患者划分为LVSD组(LVEF≤40%,n=90)及非LVSD组(LVEF40%,n=290)。另选136名健康体检者作为对照组。超声心动图测定LVEF;ELISA法测定血浆NT-proANP和NT-proB-NP浓度。描记NT-proANP和NT-proBNP预测左室收缩功能障碍受试者工作特征(ROC)曲线。依据年龄(以65岁为分界)、性别及原发心血管疾病种类划分亚组,分别描记各组患者NT-proANP和NT-proBNP预测左室收缩功能障碍ROC曲线;确定最佳cut-off值。结果病例组血浆NT-proANP和NT-proBNP浓度均显著高于对照组log(NT-proANP):(3.30±0.41)vs(2.98±0.16),P0.01;log(NT-proBNP):(2.71±0.30)vs(2.49±0.13),P0.01。NT-proANP和NT-proBNP对不同程度LVSD(LVEF≤40%或LVEF≤30%)患者诊断ROC曲线下面积(AUC)均大于0.73(P0.01);对LVEF≤40%的患者,NT-proANPAUC大于NT-proBNP(0.820vs0.738);对LVEF≤30%的患者,NT-proANPAUC明显小于NT-proBNP(0.853vs0.877)。根据各亚组ROC曲线确定cut-off值,NT-proANP为1676.92pmol/L时对各组LVSD预测敏感度88.9%～100%;特异度14.0%～58.7%;阳性预测值9.04%～30.04%;阴性预测值96.96%～98.77%。NT-proBNP为417.37pmol/L时,敏感度77.8%～94.4%;特异度10.0%～55.8%;阳性预测值7.07%～48.88%;阴性预测值94.46%～98.87%。结论 NT-proBNP与NT-proANP均能够反映心力衰竭高危人群心脏功能状态,可作为LVSD的诊断指标,对于LVEF≤40%的预测,NT-proANP效果优于NT-proBNP,有助于早期发现LVSD患者。     

Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker

CgA is a 49 kilodalton protein that is present in the secretory granules of most endocrine and many neuroendocrine cells. Detection of CgA in cells by immunocytochemistry and measurement of CgA in serum by immunoassay can serve as tissue and serum markers for CgA-producing tumors. CgA is of diagnostic value in classical endocrine tumors, in hormone-negative tumors, and in endocrine tumors in which other diagnostic procedures have their limitations. Although the biological function of CgA is yet unknown, it may serve as a precursor molecule, like POMC, for a family of biologically active peptides. CgA is an important new tool for the endocrinologist in the diagnosis and management of patients with endocrine and neuroendocrine tumors.     

Diagnostic value of plasma chromogranin A in neuroendocrine tumours

AIM: The aim of this study was to assess the value of plasma chromogranin A (CgA), a protein produced by neuroendocrine cells, in the diagnosis of neuroendocrine tumours. METHODS: Eighty subjects with neuroendocrine tumours were studied. Thirty-four had carcinoids, 21 nonfunctioning endocrine pancreatic tumours, 17 multiple endocrine neoplasia type 1 (MEN 1) (six of these also had gastrinomas), and eight had functioning pancreatic tumours (four gastrinomas, two glucagonomas, two somatostatinomas). Twenty-eight healthy subjects were studied as controls. A fasting plasma sample was obtained from each subject, and CgA plasma levels were measured by the ELISA method using a kit (Dako A/S, Denmark). RESULTS: In control subjects, plasma CgA values were below 5 U/l. Among the patients, 20 of the 34 with carcinoid tumours, 12 of the 21 with nonfunctioning pancreatic tumours, nine of the 17 with MEN 1 (including the six with gastrinomas), and the four gastrinomas of the eight functioning pancreatic tumours, i.e. overall, 45 of the 80 patients (56.3%) had abnormally high CgA values (22-961 U/l). Most of the patients with elevated CgA values, except nine of the 10 with gastrinomas, had multiple liver metastasis. CONCLUSIONS: The results show that the diagnostic value of plasma CgA in neuroendocrine tumours is relatively low; it may be of some interest only in patients with advanced disease and liver metastasis. Gastrinoma seems to be an exception, because in this tumour high CgA values are generally found even in the absence of liver metastasis.     

Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours

OBJECTIVE: To determine the interest of Chromogranin A (CgA) determination for diagnosis and follow-up in patients with gastroenteropancreatic endocrine tumours (GEP-ET) and multiple endocrine neoplasia type 1 (MEN-1). PATIENTS AND METHODS: CgA levels were measured with an immunoradiometric assay in 124 sporadic GEP-ET, 34 MEN-1 and 127 controls. Serial determinations were performed in 56 patients (212 visits). Changes in CgA levels over 25% were considered as significant. RESULTS: Using a cut-off value of 130 micro g/l, established from a receiver-operating characteristic curve, the specificity of CgA was 98.4%, with a sensitivity of 62.9%, higher in secreting than in nonsecreting tumours (73%vs. 45%; P < 0.003) and related to the extent of metastatic spreading (P < 0.001). In nonsecreting tumours, the positive predictive value (PPV) of CgA for the presence of metastases was 100% but the negative predictive value (NPV) was only 50%. In MEN-1, high CgA levels indicated a pancreatic tumour with a 100% specificity but the sensitivity was 59%. During the follow-up, the concordance between CgA and tumour evolution was 80%, whatever the secretory status. In patients with carcinoid tumours, the concordance was higher for CgA than for serotonin (81%vs. 54%; P < 0.001). CONCLUSION: Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN-1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow-up of GEP-ET tumours.     

Effects of sandostatin on plasma chromogranin-A levels in neuroendocrine tumors

We have determined the effects of Sandostatin (SMS 201-995, Sandoz) on chromogranin-A (CgA) in the blood of 14 patients with neuroendocrine tumors of the gastroenteropancreatic axis, 7 with carcinoid tumors, 5 with gastrinomas, and 1 each with a glucagonoma and tumor-secreting vasoactive intestinal peptide. Two thirds of the patients had elevated plasma CgA. Sandostatin administration suppressed CgA in 12 of the 14 patients. In 8 of 10, the clinical response to Sandostatin paralleled the reduction in CgA levels. There was a strong correlation between the change in CgA levels and the respective blood concentration of the hormone produced by the tumor. Serial measurement of CgA may provide an additional means of monitoring these tumors and their secretory activity where other measures are not available.     

Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies.

Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues. Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system. Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA. Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA. Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed. After propranolol treatment, plasma CgA remained unaltered. Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels. On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%. Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources. During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation. Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation. In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.