In addition, different CGA assays that use different antibodies or antibody combinations will display different cross-reactivity with the various CGA fragments. PPI should therefore be discontinued for at least 2 weeks before CGA measurements, because the biological effects of PPI persist for a significant time period after the drugs are discontinued. There are currently no FDA-approved chromogranin A tests. Follow-up or surveillance of patients with known or treated carcinoid tumors, An adjunct in the diagnosis of carcinoid tumors, An adjunct in the diagnosis of other neuroendocrine tumors, including pheochromocytomas, medullary thyroid carcinomas, functioning and nonfunctioning islet cell and gastrointestinal amine precursor uptake and decarboxylation tumors, and pituitary adenomas, A possible adjunct in outcome prediction and follow-up in advanced prostate cancer. Kindle Version $34.95 $8.99 Buy Now In particular, proton pump inhibitors (PPI; eg, omeprazole), which are used in the treatment of esophageal and gastroduodenal ulcer disease and dyspepsia, will result in significant elevations of serum CGA levels, often to many times above the normal range. The feedback link “Was this Article Helpful” on this page can be used to report content that is not accurate, up-to-date or questionable in any manner. A previous study in 148 pediatric patients (F=66, M=82; age range 1 day to 18 years) demonstrated that there is no significant difference in serum chromogranin A concentrations between children and adults. Get To Know What Possibly Could Be Causing Your Symptoms! If they receive input from neurons, they are called neuroendocrine cells. Suggests clinical disorders or settings where the test may be helpful, Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test. This article does not provide medical advice. Massironi S(1), Fraquelli M, Paggi S, Sangiovanni A, Conte D, Sciola V, Ciafardini C, Colombo M, Peracchi M. Author information: (1)Gastroenterology Unit II, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. In particular, when a tumor develops in an endocrine tissue, it becomes the main source of circulating CgA. (1)eval(ez_write_tag([[250,250],'epainassist_com-medrectangle-3','ezslot_6',173,'0','0']));eval(ez_write_tag([[250,250],'epainassist_com-medrectangle-3','ezslot_7',173,'0','1'])); .medrectangle-3-multi-173{border:none !important;display:block !important;float:none;line-height:0px;margin-bottom:15px !important;margin-left:0px !important;margin-right:0px !important;margin-top:15px !important;min-height:250px;min-width:250px;text-align:center !important;}, There are various causes of elevated chromogranin A (CgA) levels that are unrelated to neuroendocrine tumors. A Chromogranin A szintje a vérben általában alacsony, emelkedett szintje tünetekkel párosulva jele lehet neuroendokrin daganatnak. This assay is unlikely to be subject to hooking as it is capable of measuring CGA concentrations in excess of 1,000,000 ng/mL accurately. The elevated levels of CgA cannot be used to assess the severity or progression of disease in non-neuroendocrine neoplasms as the tumor size does not correlate with tumor size or disease progression. Major Complication In Tracheostomy & Can You Talk After A Tracheostomy Is Removed? However, lately, it has been associated with various other conditions, including both benign and malignant. The use of proton pump inhibitors and other acid-suppressive medications stimulate the growth of enterochromaffin cells to secrete CgA resulting in elevated levels of CgA in circulation. This article may contains scientific references. Chromogranin A is elevated in pheochromocytomas. Carcinoid tumors in particular almost always secrete CGA along with a variety of specific modified amines, chiefly serotonin (5-hydroxytryptamine: 5-HT) and peptides. CgA concentrations may be elevated in other conditions, such as liver disease, inflammatory bowel disease, renal insufficiency, and with stress. Eine erhöhte CgA Konzentration ist keinesfalls tumorspezifisch und findet sich bei einer Reihe von nichtmalignen Erkrankungen wie z.B.Niereninsuffizienz, Pankreatitis, chronisch entzündlichen Darmerkrankungen, Hyperparathyreoidismus, Herzinsuffizienz, Bronchitis und Stress oder bei Einnahme verschiedener Medikamente (z.B. Chromogranin A can also be increased in people who take proton pump inhibitors (PPIs), which are drugs that reduce the amount of stomach acid. Chromogranin A (CgA) Test can help with the following: Tumors, Malignant. One example is testicular cancer, which in the in-house study was associated with a mean CGA increase of 189 ng/mL. What To Expect After A Tracheostomy Is Removed? ELISA. 2010;39:753-766, 3. Pancreas. Spurious False-Low Results Due to "Hook Effect": A "hook effect" can occur at extremely high CGA concentrations, resulting in a lower measured CGA concentration than is actually contained in the specimen. It is a member of the granin family of proteins and polypeptides. It can be used both for immunohistochemical stains and as a serum marker 4.. Immunohistochemistry. Therefore, reference intervals and individual patient results differ significantly between different CGA assays and cannot be directly compared. A 100% elevation of CgA is seen in gastrinomas, 89% in pheochromocytomas, 80% in neuroendocrine tumors of the small intestine, 69% in non-functioning pancreatic neuroendocrine tumors, and >50% in medullary thyroid cancer. 2µg ($50) 10µg ($130) 1mg ($5200) Shipped with Ice Packs Add to Cart. Carcinoids display a spectrum of aggressiveness with no clear distinguishing line between benign and malignant. Blocking reagents have been added to this assay to minimize the likelihood of heterophile antibody interference. Eine Erhöhung von Chromogranin A im Serum kann verschiedene Ursachen haben. Serum CGA and urine 5-hydroxyindolacetic acid (5-HIAA) are considered the most useful biochemical markers and are first-line tests in disease surveillance of most patients with carcinoid tumors. (2), Other causes of elevated levels of CgA include hypertension, inflammatory bowel diseases, irritable bowel syndrome, pancreatitis, chronic hepatitis, liver cirrhosis, systemic rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, Parkinson’s disease, steroid treatment, food intake or strenuous exercise before a test. Det gælder ved de fleste neuroendokrine tumorer i mavetarmkanalen og bugspytkirtlen, fæokromocytomer, carcinoide … Chromogranin A fungiert als Vorläufer von verschiedenen Peptiden wie Vasostatin-1 oder Parastatin und moduliert die Bildung von sekretorischen Vesikeln. In the past, it was used in the management of patients with tumors of the gastroenteropancreatic origin. Reference values were derived from 162 donors (68 [42%] male and 94 [58%] female), ages 21 to 79. Available at www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf, 5. This includes: -Facilitating the formation of secretory granules, -Calcium- and pH-mediated sequestration and resolubilization of hormones or neurotransmitters, -Regulation of neuropeptide and peptide hormone processing through modulation of prohormone convertase activity, In addition, granins contain multiple protease and peptidase cleavage sites and, upon intra- or extracellular cleavage, give rise to a series of daughter peptides with distinct extracellular functions. The elevated levels of CgA in prostate cancer are related to progression, poor prognosis and resistance to hormonal therapy. Because of the linear relationship of CGA to tumor burden, its measurement also provides prognostic information. Limited Agreement Among Different CGA Immunoassays: There is no universal calibration standard for serum CGA assays. (2). Chromogranin A (CgA) is a member of the granin family contained in secretory vescicles of chromaffin adrenal cells. We present a case of highly elevated tenfold rise of serum chromogranin A in a young, morbidly obese, hypertensive female being investigated for pancreatic mass, weight loss, and elevated ESR. PPIs lead to increased concentrations, about 5-10 times of CgA within 5 days of medication intake, which is seen in the early stages of neuroendocrine tumors. If absolutely necessary, H2-receptor antagonists at modest doses can be substituted for PPI in such patients without risking significant false-elevations in CGA.(7). The amounts secreted are insufficient in most cases to make this a useful marker for prostate cancer diagnosis. W… The greatest value of CgA as a marker of the disease can be seen in metastatic disease to the liver. Histamine type-1 receptor antagonists are also related to increasing in CgA levels. Chromogranin A (CgA) is a protein secreted by certain hormone-producing cells, called the neuroendocrine cells. Chromogranin A levels in chronic liver disease and hepatocellular carcinoma. Consequently, serum CgA increases in patients affected by pheochromocytoma and other diseases of the chromaffin system. Can You Go Home With A Tracheostomy & Is A Tracheostomy Better Than A Ventilator? “Chromogranin A is an excellent marker for neuroendocrine tumors, particularly nonfunctioning tumors, and measurement of chromogranin A is also useful to detect prostatic carcinoma in patients whose prostate specific antigen is not elevated.” Chromogranin A in blood–a useful tumor marker Syversen U, Heide LS, Waldum HL Chromogranin A may be used to detect residual or recurrent disease in treated patients. A clue to the etiology of the hyperchromogranin A was the elevated serum gastrin level leading to suspicion of proton pump inhibitor administration confirmed by admittance to its use. Im Serum kommt Chromogranin A mit einer Konzentration von unter 102 µg/l vor. Chromogranin A belongs to the family of proteins known as grains that are mostly produced by endocrine and neuroendocrine cells. Br J Cancer. Serial measurements should be performed with the same assay or, if assays are changed, patients should have their baseline re-established. sara.massironi@libero.it Antibodies specific for chromogranin A, B or C have been used to detect immunohistochemically these three anionic proteins. CGA and its peptide fragments are cleared by a combination of hepatic metabolism and kidney excretion. What is Dupuytren’s Fasciectomy, How is it Done, Know its Complications and Recovery? This includes the differential diagnosis of isolated symptoms suggestive of carcinoid syndrome, in particular flushing. In accordance with these Wndings, serum levels of chromogranin A were elevated (4 £ upper limit of normal) and the serum liver parameters were moderately elevated. The use of PPI also compounds the effects of other conditions, listed below, that can result in false-elevations of CGA. In advanced tumors, morbidity and mortality relate as much, or more, to the biogenic amines and peptide hormones secreted, as to local and distant spread. Farlex Partner Medical Dictionary © Farlex 2012. Much smaller changes in CGA concentrations might be considered significant if they occur over several serial measurements and are all in the same direction. In this case, circulating chromogranin, serotonin, and urine 5-HIAA levels would not be elevated. 1. 2012:1-94. Carcinoid Cancer. Korse CM, Muller M, Taal BG: Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumors. Paperback $74.95 $24.95 Buy Now, Advertisement Kindle Version $8.99 Buy Now. Our articles are resourced from reputable online pages. Protonenpumpenblocker). chromogranin can be quite variable and subject to diet, prescription drugs etc. Provides information to assist in interpretation of the test results, Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances, Recommendations for in-depth reading of a clinical nature, Customized Instructions & Shipping Guides. Adjunct in Diagnosis of Carcinoid Tumors: CGA is elevated in most patients (approximately 90%) with symptomatic or advanced carcinoids (carcinoid syndrome), usually to levels several times the upper limit of the reference interval. ( krō'mō-gran'in ), A soluble and secretory hormone proteins of chromaffin granules. It is a member of the granin family of proteins and polypeptides. Other types are chromogranin 13 and secretogranin II. It regulates the activity of endocrine, paracrine, and autocrine responses Cells that release hormones are called, endocrine cells. A CgA fiziológiás körülmények között exocitózis során szabadul fel, és a vérből kimutatható lehet. Anthony LB, Stosberg JR, Klimstra DS, et al: The NANETS Consensus Guideline for the diagnosis and management of neuroendocrine tumors - Well-differentiated NETs of the distal colon and rectum. The symptoms of this carcinoid syndrome consist of flushing, diarrhea, right-sided valvular heart lesions, and bronchoconstriction. The most common causes of non-neuroendocrine tumors (false-positive result) encountered in the clinical practice is the use of proton pump inhibitors (PPIs), atrophic gastritis cases and impaired kidney function. Chromogranin A is a 49-kDa glycoprotein of the neuroendocrine system that is typically increased by stress, including hypoxia.489,549 Chromogranin A is colocalized within and co-released from storage granules along with NPY and catecholamines. Dietary Do’s and Don’ts for Migraine Sufferers, Shirshasana (Headstand) Versus Inversion Therapy Using Inversion Table, Understanding Joint Pain and Tips to Get Relief Using Home Remedies, Erectile Dysfunction: Does Opioid Cause ED, Libido: Opioid Induced Female Sexual Dysfunction. Drugs that stimulate secretion of neuroendocrine cells can lead to artifactual chromogranin A (CGA) elevations. I am asked very frequently by patients and colleagues on interpretation of CGA. These cells secrete CGA. The role of granins within the granules is to maintain the regulated secretion of these signaling molecules. Both chromogranin A and neurokinin A have been used as powerful prognostic indicators for midgut carcinoid tumors. The effects of hepatic failure are relatively minor in the absence of hepatocellular carcinoma or fulminant liver failure. in. 2012;58:941-943. This article on Epainassist.com has been reviewed by a medical professional, as well as checked for facts, to assure the readers the best possible accuracy. The sensitivity and specificity of CgA for various neuroendocrine tumors range from 60-100% and 70-100%, respectively, and the highest value is observed for serotonin-secreting neuroendocrine tumors (carcinoid tumors). Bech PR, Ramachandran R, Dhillo WS, et al: Quantifying the effects of renal impairment on plasma concentrations of the neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine- and amphetamine-regulated transcript. (2,3) Patients with foregut tumors can also be monitored with CGA or 5-HIAA measurements, if they were positive for these markers at initial diagnosis. Urine 5-hydroxyindolacetic acid (5-HIAA) and serum chromogranin A (CGA) increase in proportion to carcinoid tumor burden. It is specifically used as a biomarker in oncology. It might not be possible to provide an accurate result in some of these individuals. Boudreaux JP, Klimstra DS, Hassan MM, et al: The NANETS Consensus Guideline for the diagnosis and management of neuroendocrine tumors-Well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Caution should be kept in mind during the interpretation of chromogranin A as various factors can lead to false-positive as well as false-negative results. 2011;32:755-797, 2. 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. Kullke MH, Benson AB, Bergsland E, et al: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines): NCCN Guidelines Version 1. Granins are widespread in endocrine, neuroendocrine, peripheral, and central nervous tissues, where they are found in secretory granules alongside the tissue-specific secretion products. Some of these have defined functions, such as pancreastatin, vasostatin, and catestatin, while others are less well characterized. Chromogranin A (chromogranin, CgA), a member of the chromogranin‐secretogranin family, was first discovered as an unidentified protein in perfusate of, and in granules isolated from the adrenal medulla where it is particularly abundant. To achieve maximum sensitivity in the initial diagnosis of suspected carcinoid tumors, serum CGA, serotonin in serum or blood, and 5-HIAA in urine should all be measured. However, even modest kidney impairment can elevate serum CGA, and end-stage kidney failure is associated with elevations (in-house data: mean 471 ng/mL) similar to those observed in patients on PPI, making single serum CGA measurements uninterpretable. Therefore, it is an accepted biomarker for the assessment of neuroendocrine tumors. This article does not have the information I am looking for. A chromogranin A koncentrációja korrelál a betegség aktivitásával és a tumor méretével, a stresszhatások nem befolyásolják. In particular, CGA measurements might provide useful diagnostic information in patients with mild elevations in catecholamines and metanephrines;(6) such mild elevations often represent false-positive test results. Neuroendocrine tumors (NETs) are characterized by having behavior and prognosis that depend upon tumor histology, primary site, staging, and proliferative index. An example would be a foregut tumor that does not secrete CGA and only produces 5-hydroxytryptophan (5-HTP) rather than serotonin. Over the past 2 decades, many studies reported and confirmed that CgA was a reliable diagnostic biomarker for NETs including gastroentero-pancreatic NETs (GEP-NET) [ 1 , 3 , 5 – 20 ] and also might be a prognostic … We follow a strict editorial policy and we have a zero-tolerance policy regarding any level of plagiarism. The role of granins within the granules is to maintain the regulated secretion of these signaling molecules. 1 CgA is physiologically released by exocytosis and may be detected in the blood. These antibodies are rarely found in the normal population, but are observed at increased rates in persons with autoimmune disease or after prior sensitization to rodent proteins (eg, patients who have received diagnostic or therapeutic mouse monoclonal antibodies or animal exposure) and in case of immune system activation, such as those found following an infection, in autoimmune disease, or in some cancer patients. Hindgut tumors usually do not secrete serotonin and consequently, only CGA monitoring is recommended.(1-4). Algeciras-Schimnich A, Preissner CM, Young WF, et al: Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytomas. Clin Cancer Res. 3 Klinik. For some cases, additional tests such as urine serotonin measurement will be required. However, CGA measurements can occasionally aid in diagnosis of these tumors if specific hormone measurements are inconclusive. The sensitivity and specificity of chromogranin A in all of these conditions differ significantly that depends on various factors; therefore, its use is limited as an effective prognostic and predictive biomarker for a narrow spectrum of conditions and diseases. Such tumors are often resistant to antiandrogen therapy and have a worse prognosis. A peptide fragment of ChgA located in the Vasostatin-1, namely ChgA29-42 has been identified as the antigenic epitope recognized by diabetogenic BDC2.5 T … It is significant in the diagnosis, prognosis, clinical evaluation after cytoreductive surgery, and follow up of these tumors. Chromogranin A is particularly useful for diagnosing mid and hindgut carcinoid tumors, since they may not secrete serotonin and 5-HIAA. As is typical for tumor marker use in follow-up and surveillance, a 40% to 50% change in serum CGA concentrations should be considered potentially clinically significant in the absence of confounding factors (see Cautions). The antibodies were raised against a purified fragment containing amino acid sequence 116-439 in the chromogranin A molecule and it has been shown to measure both intact chromogranin A and fragments of chromogranin A (Stridsberg, M. et al. Bartolomucci A, Possenti R, Mahata SK, et al: The extended granin family: Structure, function, and biomedical implications. These possible causes for elevated CgA levels should be considered when interpreting test results. Chromogranins A, an acidic glycoprotein, comprises about 50% of the total protein of the granule matrix. The CLARINET trial evaluates the effects of lanreotide in patient… © 1995–2021 Mayo Foundation for Medical Education and Research. Chromogranin A (CGA) is one of the most important tests in the diagnosis of neuroendocrine tumors. Tricoli JV, Schoenfeldt M, Conley BA: Detection of prostate cancer and predicting progression: Current and future diagnostic markers. May include intervals based on age and sex when appropriate. Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease. Serum CGA measurements are particularly suited for diagnosing hindgut tumors, being elevated in nearly all cases, even though serotonin and 5-HIAA are often normal. 1993, This is the case in particular with pheochromocytoma and neuroblastoma, where CGA levels may be substantially elevated and can, therefore, provide supplementary and confirmatory information to measurements of specific hormones. The role of CGA measurement is not well defined in these tumors, with the possible exception of prognostic information in advanced prostate cancer.(5). Causes of Elevations of Serum Chromogranin A Concentration Unrelated To Carcinoids or Other Neuroendocrine Tumors. 2010;39:767-774, 4. The numbers in the parentheses (1, 2, 3) are clickable links to peer-reviewed scientific papers. Chromogranin-A Human Recombinant, His Tag PRO-699. In-house data from 1760 specimens suggest that PPI elevate CGA level on average by 757 ng/mL, but a wide range of responses is observed, with some patients showing either lesser, or far greater elevations. If an interpretive report is provided, the reference value field will state this. Describes reference intervals and additional information for interpretation of test results. Opis. Chromogranin A (CgA) is a 46-kDa glycoprotein, member of the granin family, exists within all type of neurons, normal neuroendocrine cells and is expressed in NET cells [7, 8]. CGA Fragments Interfering with Accurate Quantification: Occasional patient specimens will contain mixtures of CGA fragments that lead to nonlinearity of measurement in specimens with high concentrations of CGA that need to be diluted. Following extensive noninvasive investigations, an ultrasound-guided pancreatic biopsy confirmed benign haemorrhagic cyst. (2), CgA is the recommended first-line marker of GEP-NETs. Chromogranin A is elevated to several times the upper limit of the reference range in 90% of patients with carcinoid syndrome. 45 Chromogranin A Primary Antibodies: Thermo Fisher antibodies are validated for applications including western blotting, immunocytochemistry, flow cytometry, and chromatin immunoprecipitation. OBS Chromogranin Assays er ikke standardiserede. It is produced in neuroendocrine cells and released into the circulation. Indikationer . Granins are widespread in endocrine, neuroendocrine, peripheral, and central nervous tissues, where they are found in secretory granules alongside the tissue-specific secretion products. (2)eval(ez_write_tag([[250,250],'epainassist_com-banner-1','ezslot_4',149,'0','0']));eval(ez_write_tag([[250,250],'epainassist_com-banner-1','ezslot_5',149,'0','1'])); .banner-1-multi-149{border:none !important;display:block !important;float:none;line-height:0px;margin-bottom:15px !important;margin-left:0px !important;margin-right:0px !important;margin-top:15px !important;min-height:250px;min-width:250px;text-align:center !important;}, The neuroendocrine neoplasms, such as pheochromocytomas, parathyroid adenomas, medullary thyroid cancer, pituitary tumors (except prolactinomas), pulmonary neuroendocrine tumors including small cell lung cancer and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) secrete CgA. (1-4) Carcinoid tumors are subdivided into foregut carcinoids, arising from respiratory tract, stomach, pancreas or duodenum (approximately 15% of cases); midgut carcinoids, occurring within jejunum, ileum, or appendix (approximately 70% of cases); and hindgut carcinoids, which are found in the colon or rectum (approximately 15% of cases). Pancreas. A chromogranin A értéke emelkedett lehet pheochromocytomában, hasnyálmirigy, prosztata és … Ha a vizsgálat a betegség nyomon követésére irányul, a csökkenő CgA szint a tumor …
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