{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:51:20Z","timestamp":1790247080506,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This research was funded by grants IGA MZ CR NT\/12336-4, MH CZ - DRO (Institute of Endocrinology - E\u00da, 00023761); MZ CR 16-30345 and PROGRES Q28\/LF1 (research program of Charles University).","award":["IGA MZ CR NT\/12336-4, MH CZ - DRO (Institute of Endocrinology - E\u00da, 00023761); MZ CR 16-30345 and PROGRES Q28\/LF1 (research program of Charles University)."],"award-info":[{"award-number":["IGA MZ CR NT\/12336-4, MH CZ - DRO (Institute of Endocrinology - E\u00da, 00023761); MZ CR 16-30345 and PROGRES Q28\/LF1 (research program of Charles University)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma\/paraganglioma (PPGL). Plasma CGA (cut-off value 150 \u00b5g\/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng\/L) and normetanephrine (cut-off value 170 ng\/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.<\/jats:p>","DOI":"10.3390\/cancers11040586","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T10:44:06Z","timestamp":1556189046000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Chromogranin A in the Laboratory Diagnosis of Pheochromocytoma and Paraganglioma"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-9965","authenticated-orcid":false,"given":"Radovan","family":"B\u00edlek","sequence":"first","affiliation":[{"name":"Institute of Endocrinology, N\u00e1rodn\u00ed 8, 116 94 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Vl\u010dek","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrinology, Motol Teaching Hospital and Second Faculty of Medicine, Charles University, V \u00davalu 84, 15006 Prague 5, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libor","family":"\u0160afa\u0159\u00edk","sequence":"additional","affiliation":[{"name":"Urology Clinic, V Pra\u017esk\u00e9 br\u00e1n\u011b 74, 26601 Beroun, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Michalsk\u00fd","sequence":"additional","affiliation":[{"name":"1st Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 12808 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kv\u011btoslav","family":"Nov\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Urology, First Faculty of Medicine, Charles University and General University Hospital, Ke Karlovu 4, 12808 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-808X","authenticated-orcid":false,"given":"Jaroslava","family":"Du\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Studni\u010dkova 2, 12800 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli\u0161ka","family":"V\u00e1clav\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology, N\u00e1rodn\u00ed 8, 116 94 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Ji\u0159\u00ed","family":"Widimsk\u00fd","sequence":"additional","affiliation":[{"name":"Center for Hypertension, 3rd Medical Department-Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1, 12808 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3395-8373","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"Zelinka","sequence":"additional","affiliation":[{"name":"Center for Hypertension, 3rd Medical Department-Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1, 12808 Prague 2, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1245\/s10434-010-1006-3","article-title":"Chromogranin A-biological function and clinical utility in neuro endocrine tumor disease","volume":"17","author":"Modlin","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1470-2045(07)70410-2","article-title":"Gastroenteropancreatic neuroendocrine tumours","volume":"9","author":"Modlin","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.neo.2017.09.002","article-title":"Nothing but NET: A Review of Neuroendocrine Tumors and Carcinomas","volume":"19","author":"Oronsky","year":"2017","journal-title":"Neoplasia"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Di Giacinto, P., Rota, F., Rizza, L., Campana, D., Isidori, A., Lania, A., Lenzi, A., Zuppi, P., and Baldelli, R. (2018). Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors. Int. J. Endocrinol., 2018.","DOI":"10.1155\/2018\/8126087"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1530\/ERC-17-0269","article-title":"Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: More flaws than fame","volume":"25","author":"Marotta","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s12022-006-0003-3","article-title":"Molecular and cellular biology of pheochromocytomas and extra-adrenal paragangliomas","volume":"17","author":"Tischler","year":"2006","journal-title":"Endocr. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1210\/jc.2014-1498","article-title":"Endocrine Society. Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline","volume":"99","author":"Lenders","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","unstructured":"Pacak, K., and Tella, S.H. (2018, November 05). Pheochromocytoma and Paraganglioma, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK481899\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000074659","article-title":"Biochemical diagnosis of pheochromocytoma","volume":"31","author":"Eisenhofer","year":"2004","journal-title":"Front. Horm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Asa, S.L., Ezzat, S., and Mete, O. (2018). The Diagnosis and Clinical Significance of Paragangliomas in Unusual Locations. J. Clin. Med., 7.","DOI":"10.3390\/jcm7090280"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1097\/MPA.0b013e3181ebb4f0","article-title":"North American Neuroendocrine Tumor Society (NANETS): The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: Pheochromocytoma; paraganglioma; and medullary thyroid cancer","volume":"39","author":"Chen","year":"2010","journal-title":"Pancreas"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R109","DOI":"10.1530\/EJE-13-0882","article-title":"Diagnosis of endocrine disease: Biochemical diagnosis of phaeochromocytoma and paraganglioma","volume":"170","author":"Lenders","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ctrv.2010.07.002","article-title":"Malignant pheochromocytomas and paragangliomas\u2014The importance of a multidisciplinary approach","volume":"37","author":"Andersen","year":"2011","journal-title":"Cancer Treat. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(05)67139-5","article-title":"Phaeochromocytoma","volume":"366","author":"Lenders","year":"2005","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/er.2017-00062","article-title":"New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification","volume":"38","author":"Crona","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1530\/EC-14-0027","article-title":"Biological function and clinical relevance of chromogranin A and derived peptides","volume":"3","author":"Ghinassi","year":"2014","journal-title":"Endocr. Connect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ando.2010.04.004","article-title":"Chromogranin A assay in clinical practice","volume":"71","author":"Vezzosi","year":"2010","journal-title":"Ann. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11559","DOI":"10.1016\/S0021-9258(18)37995-X","article-title":"Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA","volume":"263","author":"Helman","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38038","DOI":"10.1074\/jbc.M604037200","article-title":"Secretory granule biogenesis in sympathoadrenal cells: Identification of a granulogenic determinant in the secretory prohormone chromogranin A","volume":"281","author":"Courel","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.regpep.2010.09.006","article-title":"Reprint of: Chromogranin A: A new proposal for trafficking; processing and induction of granule biogenesis","volume":"165","author":"Koshimizu","year":"2010","journal-title":"Regul. Pept."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00424-017-2030-y","article-title":"Circulating chromogranin A and its fragments as diagnostic and prognostic disease markers","volume":"470","author":"Corti","year":"2018","journal-title":"Pflugers Arch."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1471-4159.2010.06786.x","article-title":"Chromogranins as regulators of exocytosis","volume":"114","author":"Borges","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1096\/fj.09-132456","article-title":"Secretory granules in inositol 1;4;5-trisphosphate-dependent Ca2+ signaling in the cytoplasm of neuroendocrine cells","volume":"24","author":"Yoo","year":"2010","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1152\/physrev.1999.79.2.361","article-title":"Vacuolar and plasma membrane proton-adenosinetriphosphatases","volume":"79","author":"Nelson","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kimura, N., Takekoshi, K., and Naruse, M. (2018). Risk Stratification on Pheochromocytoma and Paraganglioma from Laboratory and Clinical Medicine. J. Clin. Med., 7.","DOI":"10.20944\/preprints201807.0478.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/eci.12245","article-title":"Clinical utility of chromogranin A in SDHx-related paragangliomas","volume":"44","author":"Zuber","year":"2014","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/00000478-200205000-00002","article-title":"Phaeochromocytoma of the adrenal gland scoring scale (PASS) to separate benign from malignant neoplasms. A clinicopathologic and immunophenotypic study of 100 cases","volume":"26","author":"Thompson","year":"2002","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s12020-010-9422-5","article-title":"Malignant pheochromocytoma: Predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center","volume":"39","author":"Szalat","year":"2011","journal-title":"Endocrine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yang, X., Yang, Y., Li, Z., Cheng, C., Yang, T., Wang, C., Liu, L., and Liu, S. (2015). Diagnostic value of circulating chromogranin a for neuroendocrine tumors: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124884"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S171","DOI":"10.33549\/physiolres.931502","article-title":"Chromogranin A; a member of neuroendocrine secretory proteins as a selective marker for laboratory diagnosis of pheochromocytoma","volume":"57","author":"Bilek","year":"2008","journal-title":"Physiol. Res."},{"key":"ref_31","first-page":"993","article-title":"Chromogranin A assay and (131)I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma","volume":"42","author":"Gouze","year":"2001","journal-title":"J. Nucl. Med."},{"key":"ref_32","first-page":"344","article-title":"Chromogranin A immunoradiometric assay in diagnosis of pheochromocytoma: Comparison with plasma metanephrines and 123I-MIBG scan","volume":"50","author":"Giovanella","year":"2006","journal-title":"Q. J. Nucl. Med. Mol. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/MPA.0b013e3181ebaffd","article-title":"North American Neuroendocrine Tumor Society (NANETS). NANETS consensus guidelines for the diagnosis of neuroendocrine tumor","volume":"39","author":"Vinik","year":"2010","journal-title":"Pancreas"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.archger.2009.08.004","article-title":"Chromogranin A (CgA) serum level as a marker of progression in hepatocellular carcinoma (HCC) of elderly patients","volume":"51","author":"Malaguarnera","year":"2010","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ecl.2010.12.001","article-title":"The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumors","volume":"40","author":"Lawrence","year":"2011","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Giovinazzo, F., Schimmack, S., Svejda, B., Alaimo, D., Pfragner, R., Modlin, I., and Kidd, M. (2013). Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081111"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/bjc.2011.380","article-title":"Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours","volume":"105","author":"Korse","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E1731","DOI":"10.1210\/jc.2012-1548","article-title":"Effect of short-term proton pump inhibitor treatment and its discontinuation on chromogranin A in healthy subjects","volume":"97","author":"Mosli","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/clinchem\/35.8.1631","article-title":"Rapid radioimmunoassay of circulating chromogranin A: In vitro stability; exploration of the neuroendocrine character of neoplasia; and assessment of the effects of organ failure","volume":"35","author":"Pandlan","year":"1989","journal-title":"Clin. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e461","DOI":"10.5301\/ijbm.5000278","article-title":"Reference limits for chromogranin A; CYFRA 21\u20131; CA 125; CA 19\u20139 and carcinoembryonic antigen in patients with chronic kidney disease","volume":"32","author":"Mikkelsen","year":"2017","journal-title":"Int. J. Biol. Markers"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1530\/eje.1.01862","article-title":"Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis; enterochromaffin-like cell lesions and gastric carcinoids","volume":"152","author":"Peracchi","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.dld.2008.05.002","article-title":"Chromogranin A levels in chronic liver disease and hepatocellular carcinoma","volume":"41","author":"Massironi","year":"2009","journal-title":"Dig. Liver. Dis."},{"key":"ref_43","first-page":"23","article-title":"The role of serum chromogranin A in diarrhoea predominant irritable bowel syndrome","volume":"18","author":"Sidhu","year":"2009","journal-title":"J. Gastrointestin. Liver. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ahj.2006.05.008","article-title":"Prognostic value of plasma chromogranin A levels in patients with complicated myocardial infarction","volume":"152","author":"Estensen","year":"2006","journal-title":"Am. Heart J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/eurheartj\/ehn513","article-title":"Prognostic value of circulating chromogranin A levels in acute coronary syndromes","volume":"30","author":"Jansson","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1055\/s-0032-1306294","article-title":"High incidence of cardiovascular complications in pheochromocytoma","volume":"44","author":"Zelinka","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S397","DOI":"10.33549\/physiolres.933719","article-title":"Radioimmunoassay of chromogranin A and free metanephrines in diagnosis of pheochromocytoma","volume":"66","author":"Bilek","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1373\/clinchem.2004.045484","article-title":"Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines","volume":"51","author":"Eisenhofer","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1365-2265.2010.03914.x","article-title":"Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas","volume":"74","author":"Kema","year":"2011","journal-title":"Clin. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Stenman, A., Zedenius, J., and Juhlin, C.C. (2019). The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas. A Meta-Analysis and Systematic Review of the Literature. Cancers, 11.","DOI":"10.3390\/cancers11020225"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-16-0033","article-title":"European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma","volume":"174","author":"Plouin","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14414","DOI":"10.1016\/S0021-9258(18)77318-3","article-title":"Ca2(+)-induced conformational change and aggregation of chromogranin A","volume":"265","author":"Yoo","year":"1990","journal-title":"J. Biol. Chem."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/4\/586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:47:11Z","timestamp":1760186831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/4\/586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,25]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["cancers11040586"],"URL":"https:\/\/doi.org\/10.3390\/cancers11040586","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,25]]}}}