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      Urinary and Plasma Catecholamines and Metanephrines in Dogs with Pheochromocytoma, Hypercortisolism, Nonadrenal Disease and in Healthy Dogs

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          Abstract

          Background

          Diagnosis of pheochromocytoma ( PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine.

          Objectives

          To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC.

          Animals

          Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs.

          Methods

          Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at −80°C before analysis using high‐pressure liquid chromatography ( HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration.

          Results

          Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma‐total and free normetanephrine and plasma‐free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma.

          Conclusion and clinical importance

          Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.

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          Most cited references29

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          Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005.

          The First International Symposium on Pheochromocytoma, held in October 2005, included discussions about developments concerning these rare catecholamine-producing tumors. Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment. Measurement of plasma or urinary fractionated metanephrines, the most accurate screening approach, was recommended as the first-line test for diagnosis; reference intervals should favor sensitivity over specificity. Localization studies should only follow reasonable clinical evidence of a tumor. Preoperative pharmacologic blockade of circulatory responses to catecholamines is mandatory. Because approximately a quarter of tumors develop secondary to germ-line mutations in any one of five genes, mutation testing should be considered; however, it is not currently cost effective to test every gene in every patient. Consideration of tumor location, presence of multiple tumors, presence of metastases, and type of catecholamine produced is useful in deciding which genes to test. Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.
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            Catecholamines, infection, and death in acute ischemic stroke.

            Experimental studies have recently suggested that acute ischemia may facilitate the appearance of fatal infections as part of a brain-induced immunodepression syndrome. However, the mechanisms and neurological consequences of infections complicating acute ischemic stroke have received much less attention at the bedside. The incidence of infection and death after non-septic stroke was compared in this prospective study with longitudinal changes of cytokines, leukocytes, normetanephrine (NMN) and metanephrine (MN) in 75 consecutive patients. In multivariate analysis, infection, n = 13 (17%), was associated with the upper quartile of MN (OR 3.51, 95% CI 1.30-9.51), neurological impairment (NIHSS) on admission (OR 3.99, 95% CI 1.34-11.8), monocyte count (OR 1.78, 95% CI 1.13-2.79), and increased interleukin (IL)-10 (OR 1.54, 95% CI 1.00-2.38). Mortality at 3 months, n = 16 (21%), was associated with increased levels of NMN on admission (OR 2.34 95% CI 1.15-4.76), NIHSS score (OR 2.57, 95% CI 1.29-5.11), and higher IL-6 levels (OR 1.29, 95% 1.00-1.67). These findings suggest that acute ischemic stroke is associated with an early activation of the sympathetic adrenomedullar pathway that lowers the threshold of infection and increases the risk of death. Moreover, these findings are independent of the blood borne effects of pro- and anti-inflammatory cytokines, and circulating leukocytes.
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              A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines.

              We compared the diagnostic efficacy of fractionated plasma metanephrine measurements to measurements of 24-h urinary total metanephrines and catecholamines in outpatients tested for pheochromocytoma at Mayo Clinic Rochester from January 1, 1999, until November 27, 2000. Catecholaminesecreting tumors were histologically proven. The sensitivity of fractionated plasma metanephrines was 97% (30 of 31 patients), compared with a sensitivity of 90% (28 of 31) for urinary total metanephrines and catecholamines (P = 0.63). The specificity of fractionated plasma metanephrines was 85% (221 of 261), compared with 98% (257 of 261; P < 0.001) for urinary measurements. The likelihood ratios for positive tests were 6.3 (95% confidence interval, 4.7 to 8.5) for fractionated plasma metanephrines and 58.9 (95% confidence interval, 22.1 to 156.9) for urinary total metanephrines and catecholamines. An adrenal pheochromocytoma was missed by urinary testing in two patients with familial syndromes and one asymptomatic patient with an incidentally discovered adrenal mass. An extra-adrenal paraganglioma was missed by plasma testing in one patient. In conclusion, measurements of 24-h urinary total metanephrines and catecholamines yield fewer false-positive results, an attribute preferred for testing low-risk patients, but fractionated plasma metanephrine measurements may be preferred in high-risk patients with familial endocrine syndromes.
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                Author and article information

                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0891-6640
                1939-1676
                27 March 2015
                Mar-Apr 2015
                : 29
                : 2 ( doiID: 10.1111/jvim.2015.29.issue-2 )
                : 597-602
                Affiliations
                [ 1 ] Clinic for Small Animal Internal Medicine Vetsuisse FacultyUniversity of Zurich ZurichSwitzerland
                [ 2 ] Institute of Clinical ChemistryUniversity Hospital Zurich ZurichSwitzerland
                [ 3 ] Clinical Laboratory Vetsuisse FacultyUniversity of Zurich ZurichSwitzerland
                [ 4 ] Division of Diagnostic Imaging Vetsuisse FacultyUniversity of Zurich ZurichSwitzerland
                [ 5 ] Service of BiomedicineUniversity Hospital Vaudois LausanneSwitzerland
                Author notes
                [*] [* ]Corresponding author: F.S. Boretti, Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstr. 260, 8057 Zurich, Switzerland; e‐mail: fboretti@ 123456vetclinics.uzh.ch .
                Article
                JVIM12569
                10.1111/jvim.12569
                4895504
                25818214
                9c209bc6-681b-4e9d-aaf6-0feee2f792ec
                Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 26 January 2014
                : 27 November 2014
                : 03 February 2015
                Page count
                Pages: 6
                Categories
                Standard Article
                Standard Articles
                Custom metadata
                2.0
                jvim12569
                March/April 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:06.05.2016

                Veterinary medicine
                canine,diagnosis,hyperadrenocorticism,mass spectrometry
                Veterinary medicine
                canine, diagnosis, hyperadrenocorticism, mass spectrometry

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