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      Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations

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          Abstract

          Context

          Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours.

          Objective

          To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays.

          Methods

          Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences.

          Results

          5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.).

          Conclusion

          Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays.

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          Most cited references110

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          Catecholamine metabolism: a contemporary view with implications for physiology and medicine.

          This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states.
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            Consensus on biomarkers for neuroendocrine tumour disease

            Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours.
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              The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum.

              Well-differentiated neuroendocrine tumors (NETs) of the jejunum, ileum, and appendix are also collectively known as midgut carcinoids. Similar to NETs in general, the diagnosed incidence of the midgut NETs is on the rise. Their presenting symptoms vary depending on stage and primary site. Local-regional NETs often present with vague and nonspecific symptoms. Classic carcinoid syndrome is more likely to appear in patients with advanced disease. Local-regional NETs of the small bowel should be resected whenever possible. With the exception of small well-differentiated NETs of the appendix, NETs of the midgut have substantial risk of relapse after resection and need to be followed for at least 7 years.Metastatic/advanced NETs of the midgut are incurable. Optimal management requires a multidisciplinary approach. Somatostatin analogs are effective in the management of carcinoid syndrome. Octreotide long-acting release has also recently been shown to delay disease progression. Liver-directed therapy and surgical debulking can improve quality of life in selected patients. Pivotal phase 3 studies with bevacizumab targeting vascular endothelial growth factor and everolimus targeting mTOR (mammalian target of rapamycin) are ongoing and may lead to improved outcome. Further studies of novel approaches such as peptide receptor radiotherapy are also warranted.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                August 2017
                31 May 2017
                : 6
                : 6
                : R87-R98
                Affiliations
                [1 ]Department of Nuclear Medicine Haut Lévêque Hospital, Pessac, France
                [2 ]Nutrition et Neurobiologie intégrée UMR 1286, University of Bordeaux, Bordeaux, France
                [3 ]Groupe de Biologie Spécialisée Société Française de Médecine Nucléaire, Paris, France
                [4 ]Department of Biochemistry Edouard Herriot Hospital, Lyon, France
                [5 ]Biomnis Lyon, France
                Author notes
                Correspondence should be addressed to J-B Corcuff; Email: jean-benoit.corcuff@ 123456u-bordeaux.fr
                Article
                EC170071
                10.1530/EC-17-0071
                5527357
                28566493
                386dec89-0ab4-4382-be22-f48bbc42bfe4
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 3 May 2017
                : 30 May 2017
                Categories
                Review

                5-hydroxy indole acetic acid,metanephrines,assay,neuroendocrine tumours

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