{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T13:10:20Z","timestamp":1756818620495,"version":"3.44.0"},"reference-count":29,"publisher":"American Veterinary Medical Association (AVMA)","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To examine the normetanephrine- and metanephrine-to-creatinine urinary fractionation ratios of clouded leopards (<jats:italic>Neofelis nebulosa<\/jats:italic>) at various ages. We hypothesized that clouded leopards with large metanephrine- and\/or normetanephrine-to-creatinine fractionation ratios would have a pheochromocytoma on postmortem examination. Those subjects with comparatively smaller fractionation ratios would not have a pheochromocytoma on postmortem examination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Clouded leopards housed at a zoological institution or sanctuary were included in this study. Patients were examined within a hospital environment. All samples were obtained from January 2020 through August 2021. Urine was collected from patients by direct free catch, cystocentesis, or urinary catheterization and analyzed for metanephrine- and normetanephrine-to-creatinine fractionation ratios. Postmortem examinations were performed on animals that died naturally or were euthanized for various comorbidities to determine if a pheochromocytoma was present.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>This experimental study included 1- to 16-year-old clouded leopards, 11 male and 6 female, managed under human care. The 2 clouded leopards in this study with normetanephrine- or metanephrine-to-creatinine fractionation ratios greater than 4 times the high end of the ranges identified in the subjects of this study had confirmed pheochromocytomas on postmortem examination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Normetanephrine- and metanephrine-to-creatinine fractionation testing may be useful tools in the antemortem diagnosis of pheochromocytomas in clouded leopards.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>Normetanephrine- and metanephrine-to-creatinine fractionation testing may provide a minimally invasive antemortem method of screening for pheochromocytomas in clouded leopards. Quantitative studies are needed to determine if this testing is consistently able to diagnose pheochromocytoma in live clouded leopards.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.25.01.0033","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T15:26:38Z","timestamp":1750087598000},"source":"Crossref","is-referenced-by-count":0,"title":["Assessment of urinary metanephrine and normetanephrine fractionation analyses as aids in the antemortem diagnosis of pheochromocytomas in clouded leopards (Neofelis nebulosa)"],"prefix":"10.2460","volume":"86","author":[{"given":"Peter A.","family":"Sojka","sequence":"first","affiliation":[{"name":"Avian and Exotics Department, Pieper Memorial Veterinary Hospital, Middletown, CT"},{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Cushing","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Martinelli","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Nashville Zoo at Grassmere, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward C.","family":"Ramsay","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"B1","series-title":"In: The IUCN Red List of Threatened Species","first-page":"e.T14519A198843258","article-title":"Neofelis nebulosa","author":"Gray T","year":"2021","unstructured":"Gray T, Borah J, Coudrat CNZ, et al. Neofelis nebulosa. In: The IUCN Red List of Threatened Species. 2021:e.T14519A198843258. doi:10.2305\/IUCN.UK.2021-2.RLTS.T14519A198843258.en"},{"year":"2019","key":"B2","unstructured":"Clouded leopard birth includes two much-needed males. ZooBorns. May 11, 2019. Accessed May 13, 2025. https:\/\/www.zooborns.com\/zooborns\/2019\/05\/clouded-leopard-birth-includes-two-much-needed-males.html"},{"issue":"1","key":"B3","series-title":"Anim Biol","first-page":"95","article-title":"Spontaneous neoplasms in zoo mammals, birds, and reptiles in Taiwan \u2013 a 10-year survey","author":"Chang PH","year":"2012","unstructured":"Chang PH, Liu CH, Jeng CR, et al. Spontaneous neoplasms in zoo mammals, birds, and reptiles in Taiwan \u2013 a 10-year survey. Anim Biol. 2012;62(1):95\u2013110. doi:10.1163\/157075611X616941"},{"issue":"2","key":"B4","series-title":"Vet Pathol","first-page":"269","article-title":"Histologic and immunohistochemical characterization of pheochromocytomas in 20 clouded leopards (Neofelis nebulosa)","author":"Corner S","year":"2017","unstructured":"Corner S, Walsh T, Padilla L, et al. Histologic and immunohistochemical characterization of pheochromocytomas in 20 clouded leopards (Neofelis nebulosa). Vet Pathol. 2017;54(2):269\u2013276. doi:10.1177\/0300985816664791"},{"issue":"2","key":"B5","series-title":"J Zoo Wildl Med","first-page":"413","article-title":"A retrospective study of neoplasia in nondomestic felids in human care, with a comparative literature review","author":"Mathieu A","year":"2021","unstructured":"Mathieu A, Garner MM. A retrospective study of neoplasia in nondomestic felids in human care, with a comparative literature review. J Zoo Wildl Med. 2021;52(2):413\u2013426. doi:10.1638\/2020-0077"},{"issue":"1","key":"B6","series-title":"J Zoo Wildl Med","first-page":"150","article-title":"Clouded leopard (Neofelis nebulosa) morbidity and mortality in captive-bred populations: a comprehensive retrospective study of medical data from 271 individuals in European, Asian, and Australian zoos","author":"Thorel M","year":"2020","unstructured":"Thorel M, Pignon C, Arne P, Donnelly TM, Rivi\u00e8re J. Clouded leopard (Neofelis nebulosa) morbidity and mortality in captive-bred populations: a comprehensive retrospective study of medical data from 271 individuals in European, Asian, and Australian zoos. J Zoo Wildl Med. 2020;51(1):150\u2013158. doi:10.1638\/2019-0048"},{"issue":"1","key":"B7","series-title":"BMC Vet Res","first-page":"3","article-title":"Favorable outcome of pheochromocytoma in a dog with atypical Cushing\u2019s syndrome and diabetes mellitus following medical treatment: a case report","author":"Lee GW","year":"2020","unstructured":"Lee GW, Yoo CR, Lee D, Park M. Favorable outcome of pheochromocytoma in a dog with atypical Cushing\u2019s syndrome and diabetes mellitus following medical treatment: a case report. BMC Vet Res. 2020;16(1):3. doi:10.1186\/s12917-019-2225-x"},{"issue":"6","key":"B8","series-title":"J Vet Diagn Investig","first-page":"887","article-title":"Evaluation of an ELISA for metanephrines in feline urine","author":"Srithunyarat T","year":"2018","unstructured":"Srithunyarat T, Svensson A, Han\u00e5s S, et al. Evaluation of an ELISA for metanephrines in feline urine. J Vet Diagn Investig. 2018;30(6):887\u2013893. doi:10.1177\/1040638718793168"},{"issue":"5","key":"B9","series-title":"J Clin Endocrinol Metab","first-page":"2023","article-title":"A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma","author":"Waguespack SG","year":"2010","unstructured":"Waguespack SG, Rich T, Grubbs E, et al. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010;95(5):2023\u20132037. doi:10.1210\/jc.2009-2830"},{"key":"B10","series-title":"Withrow & MacEwen\u2019s Small Animal Clinical Oncology","first-page":"565","article-title":"Tumors of the endocrine system","author":"Lunn KF","year":"2020","unstructured":"Lunn KF, Boston SE. Tumors of the endocrine system. In: Vail DM, Thamm DH, Liptak JM, eds. Withrow & MacEwen\u2019s Small Animal Clinical Oncology. Vol 6. Saunders Elsevier; 2020:565\u2013596."},{"issue":"4","key":"B11","series-title":"Vet Comp Oncol","first-page":"1158","article-title":"Pheochromocytomas and paragangliomas in humans and dogs","author":"Galac S","year":"2017","unstructured":"Galac S, Korpershoek E. Pheochromocytomas and paragangliomas in humans and dogs. Vet Comp Oncol. 2017;15(4):1158\u20131170. doi:10.1111\/vco.12291"},{"issue":"2","key":"B12","series-title":"J Vet Intern Med","first-page":"597","article-title":"Urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma, hypercortisolism, nonadrenal disease and in healthy dogs","author":"Salesov E","year":"2015","unstructured":"Salesov E, Boretti FS, Sieber-Ruckstuhl NS, et al. Urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma, hypercortisolism, nonadrenal disease and in healthy dogs. J Vet Intern Med. 2015;29(2):597\u2013602. doi:10.1111\/jvim.12569"},{"issue":"3","key":"B13","series-title":"J Vet Intern Med","first-page":"e70021","article-title":"Cytologic evaluation as a diagnostic tool to differentiate adrenocortical tumors and pheochromocytomas","author":"Piegols HJ","year":"2025","unstructured":"Piegols HJ, Williams RW, Pathak N, et al. Cytologic evaluation as a diagnostic tool to differentiate adrenocortical tumors and pheochromocytomas. J Vet Intern Med. 2025;39(3):e70021. doi:10.1111\/jvim.70021"},{"issue":"1","key":"B14","series-title":"J Vet Intern Med","first-page":"83","article-title":"Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs","author":"Gostelow R","year":"2013","unstructured":"Gostelow R, Bridger N, Syme HM. Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs. J Vet Intern Med. 2013;27(1):83\u201390. doi:10.1111\/jvim.12009"},{"year":"2022","author":"Alexandre MT","key":"B15","unstructured":"Alexandre MT. Plasma and Urinary Metanephrine and Normetanephrine in Healthy Cats \u2013 a Pilot Study. Master\u2019s thesis. Universidade de Lisboa; 2022."},{"author":"Leary S","key":"B16","unstructured":"Leary S, Underwood W, Anthony R, et al. AVMA guidelines for the euthanasia of animals: 2020 edition. AVMA. Accessed May 13, 2025. https:\/\/www.avma.org\/sites\/default\/files\/2020-02\/Guidelines-on-Euthanasia-2020.pdf"},{"issue":"5","key":"B17","series-title":"J Vet Intern Med","first-page":"1093","article-title":"Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs","author":"Quante S","year":"2010","unstructured":"Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med. 2010;24(5):1093\u20131097. doi:10.1111\/j.1939-1676.2010.0578.x"},{"key":"B18","series-title":"J Chromatogr B Analyt Technol Biomed Life Sci","first-page":"83","article-title":"Comprehensive, robust, and sensitive UPLC-MS\/MS analysis of free biogenic monoamines and their metabolites in urine","author":"Xie Z","year":"2018","unstructured":"Xie Z, Lorkiewicz P, Riggs DW, Bhatnagar A, Srivastava S. Comprehensive, robust, and sensitive UPLC-MS\/MS analysis of free biogenic monoamines and their metabolites in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1099:83\u201391. doi:10.1016\/j.jchromb.2018.09.012"},{"issue":"1","key":"B19","series-title":"J Pharmacol Exp Ther","first-page":"15","article-title":"Distribution of metanephrine and normetanephrine in various animals and their analysis in diverse biologic material","author":"Anton AH","year":"1966","unstructured":"Anton AH, Sayre DF. Distribution of metanephrine and normetanephrine in various animals and their analysis in diverse biologic material. J Pharmacol Exp Ther. 1966;153(1):15\u201329. doi:10.1016\/S0022-3565(25)27358-X"},{"issue":"6","key":"B20","series-title":"Vet Rec","first-page":"169","article-title":"Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma","author":"Kook PH","year":"2010","unstructured":"Kook PH, Grest P, Quante S, Boretti FS, Reusch CE. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec. 2010;166(6):169\u2013174. doi:10.1136\/vr.b4760"},{"issue":"3","key":"B21","series-title":"J Am Vet Med Assoc","first-page":"359","article-title":"High specificity and sensitivity of spot urine normetanephrine-to-creatinine ratios in the diagnosis of canine pheochromocytoma","author":"Waldron C","year":"2025","unstructured":"Waldron C, Thamm DH, Watson-Skaggs M, Vinayak A. High specificity and sensitivity of spot urine normetanephrine-to-creatinine ratios in the diagnosis of canine pheochromocytoma. J Am Vet Med Assoc. 2025;263(3):359\u2013367. doi:10.2460\/javma.24.06.0409"},{"issue":"3","key":"B22","series-title":"J Vet Intern Med","first-page":"388","article-title":"Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma","author":"Kook PH","year":"2007","unstructured":"Kook PH, Boretti FS, Hersberger M, Glaus TM, Reusch CE. Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma. J Vet Intern Med. 2007;21(3):388\u2013393. doi:10.1111\/j.1939-1676.2007.tb02980.x"},{"issue":"3","key":"B23","series-title":"J Vet Intern Med","first-page":"910","article-title":"Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma","author":"Prego MT","year":"2023","unstructured":"Prego MT, Dias MJ, Ferreira RL, et al. Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma. J Vet Intern Med. 2023;37(3):910\u2013914. doi:10.1111\/jvim.16648"},{"issue":"6","key":"B24","series-title":"J Small Anim Pract","first-page":"415","article-title":"Diagnosis, treatment and outcome of pheochromocytoma in a cat","author":"Prego MT","year":"2023","unstructured":"Prego MT, Dias MJ, Mestrinho L, et al. Diagnosis, treatment and outcome of pheochromocytoma in a cat. J Small Anim Pract. 2023;64(6):415\u2013420. doi:10.1111\/jsap.13601"},{"issue":"2","key":"B25","series-title":"Clin Chem","first-page":"268","article-title":"Stability of urinary fractionated metanephrines and catecholamines during collection, shipment, and storage of samples","author":"Willemsen JJ","year":"2007","unstructured":"Willemsen JJ, Ross HA, Lenders JWM, Sweep FCGJ. Stability of urinary fractionated metanephrines and catecholamines during collection, shipment, and storage of samples. Clin Chem. 2007;53(2):268\u2013272. doi:10.1373\/clinchem.2006.075218"},{"issue":"6","key":"B26","series-title":"J Feline Med Surg","first-page":"435","article-title":"Plasma free metanephrines in healthy cats, cats with non-adrenal disease and a cat with suspected phaeochromocytoma","author":"Wimpole JA","year":"2010","unstructured":"Wimpole JA, Adagra CFM, Billson MF, Pillai DN, Foster DJ. Plasma free metanephrines in healthy cats, cats with non-adrenal disease and a cat with suspected phaeochromocytoma. J Feline Med Surg. 2010;12(6):435\u2013440. doi:10.1016\/j.jfms.2009.10.010"},{"issue":"3","key":"B27","series-title":"Vet Surg","first-page":"438","article-title":"Short- and long-term survival after adrenalectomy in 53 dogs with pheochromocytomas with or without alpha-blocker therapy","author":"Enright D","year":"2022","unstructured":"Enright D, Dickerson VM, Grimes JA, Townsend S, Mankin KMT. Short- and long-term survival after adrenalectomy in 53 dogs with pheochromocytomas with or without alpha-blocker therapy. Vet Surg. 2022;51(3):438\u2013446. doi:10.1111\/vsu.13771"},{"issue":"6","key":"B28","series-title":"J Vet Intern Med","first-page":"1333","article-title":"Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma","author":"Herrera MA","year":"2008","unstructured":"Herrera MA, Mehl ML, Kass PH, Pascoe PJ, Feldman EC, Nelson RW. Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma. J Vet Intern Med. 2008;22(6):1333\u20131339. doi:10.1111\/j.1939-1676.2008.0182.x"},{"issue":"1","key":"B29","series-title":"BMC Vet Res","first-page":"272","article-title":"Retrospective evaluation of toceranib phosphate (Palladia) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014\u20132017)","author":"Musser ML","year":"2018","unstructured":"Musser ML, Taikowski KL, Johannes CM, Bergman PJ. Retrospective evaluation of toceranib phosphate (Palladia) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014\u20132017). BMC Vet Res. 2018;14(1):272. doi:10.1186\/s12917-018-1597-7"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/9\/ajvr.25.01.0033.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/9\/ajvr.25.01.0033.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/9\/ajvr.25.01.0033.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T12:36:48Z","timestamp":1756816608000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/9\/ajvr.25.01.0033.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":29,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.25.01.0033","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"type":"print","value":"0002-9645"},{"type":"electronic","value":"1943-5681"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}