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      Elevated Inflammation Markers in Pheochromocytoma Compared to Other Forms of Hypertension

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          Abstract

          Objective: To investigate the effect of long-term catecholamine excess in pheochromocytoma on leukocyte and platelet count and on proteins of acute-phase response. Methods: Fifteen subjects with pheochromocytoma, 16 with primary aldosteronism, 18 with essential hypertension and 17 healthy controls were studied. Sixteen subjects with pheochromocytoma were investigated after tumor removal. Leukocyte, neutrophil and platelet count, as well as C-reactive protein were measured in all subjects, while fibrinogen, α<sub>1</sub>-antitrypsin, α<sub>2</sub>-macroglobulin, orosomucoid, transferrin and prealbumin were only measured in subjects with pheochromocytoma, primary aldosteronism and essential hypertension. Results: Subjects with pheochromocytoma showed significantly higher leukocyte [7.5 ± 0.9 10<sup>9</sup>/l, p < 0.001 vs. primary aldosteronism (5.4 ± 0.9 10<sup>9</sup>/l) and healthy controls (5 ± 0.9 10<sup>9</sup>/l), p = 0.04 vs. essential hypertension (6.3 ± 1.6 10<sup>9</sup>/l)], neutrophil (p < 0.001 vs. primary aldosteronism and healthy subjects) and platelet counts (p < 0.001 vs. primary aldosteronism; p = 0.01 vs. essential hypertension) compared to the other groups of subjects. Similar results were obtained for positive proteins of acute-phase response in subjects with pheochromocytoma [C-reactive protein: 0.62 ± 0.52 mg/dl, p < 0.001 vs. healthy subjects (0.08 ± 0.08 mg/dl), p = 0.001 vs. primary aldosteronism (0.17 ± 0.19 mg/dl), p = 0.04 vs. essential hypertension (0.31 ± 0.26 mg/dl); fibrinogen: p = 0.02 vs. primary aldosteronism; orosomucoid: p = 0.005 vs. primary aldosteronism; α<sub>2</sub>-macroglobulin: p = 0.009 vs. primary aldosteronism]. No significant differences were found in plasma levels of α<sub>1</sub>-antitrypsin, transferrin and prealbumin. Tumor removal led to a significant decrease in leukocyte (p = 0.004), neutrophil (p = 0.007) and platelet count (p = 0.003) and also to a significant decrease in acute-phase proteins (C-reactive protein: p = 0.03, fibrinogen: p = 0.008, α<sub>1</sub>-antitrypsin: p = 0.003, orosomucoid: p = 0.04). Conclusions: Chronic catecholamine excess in pheochromocytoma is accompanied by an increase in inflammation markers which was reversed by the tumor removal.

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          Phaeochromocytoma.

          Phaeochromocytomas are rare neuroendocrine tumours with a highly variable clinical presentation but most commonly presenting with episodes of headaches, sweating, palpitations, and hypertension. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines. Biochemical testing for phaeochromocytoma is indicated not only in symptomatic patients, but also in patients with adrenal incidentalomas or identified genetic predispositions (eg, multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and mutations of the succinate dehydrogenase genes). Imaging techniques such as CT or MRI and functional ligands such as (123)I-MIBG are used to localise biochemically proven tumours. After the use of appropriate preoperative treatment to block the effects of secreted catecholamines, laparoscopic tumour removal is the preferred procedure. If removal of phaeochromocytoma is timely, prognosis is excellent. However, prognosis is poor in patients with metastases, which especially occur in patients with large, extra-adrenal tumours.
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            The acute phase response.

            Adult mammals respond to tissue damage by implementing the acute phase response, which comprises a series of specific physiological reactions. This review outlines the principal cellular and molecular mechanisms that control initiation of the tissue response at the site of injury, the recruitment of the systemic defense mechanisms, the acute phase response of the liver and the resolution of the acute phase response.
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              Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.

              There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2007
                August 2007
                15 August 2007
                : 14
                : 1
                : 57-64
                Affiliations
                a3rd Department of Medicine and bCentral Hematological Laboratories, General Faculty Hospital, Praha, Czech Republic; cSection of Medical Neuroendocrinology, Reproductive and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA
                Article
                107289 Neuroimmunomodulation 2007;14:57–64
                10.1159/000107289
                17700041
                b1ccc070-fadf-436f-bd9f-12cc6fe151db
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 24 November 2006
                : 13 March 2007
                Page count
                Tables: 4, References: 50, Pages: 8
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Catecholamines,Inflammation,Pheochromocytoma

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