{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:42:48Z","timestamp":1782276168053,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T00:00:00Z","timestamp":1546560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>The current clinical investigation for primary aldosteronism (PA) diagnosis requires complex expensive tests from the initial suspicion to the final subtype classification, including invasive approaches; therefore, appropriate markers for subtype definition are greatly desirable. The present study performs a metabolomics analysis to further examine specific molecular signatures of PA urines<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental design<\/jats:title><jats:p>The study considered PA subtype and gender\u2010related differences using two orthogonal advanced UHPLC\u2010MS metabolomics approaches. Patients with essential hypertension (<jats:italic>n<\/jats:italic> = 36) and PA (<jats:italic>n<\/jats:italic> = 50) who were referred to the outpatient hypertension clinic and matched healthy subjects (<jats:italic>n<\/jats:italic> = 10) are investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Statistically significant changes (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 ANOVA, Fc\u00a0&gt;\u00a01.5) of metabolites involved in central carbon, energy, and nitrogen metabolism are identified, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS\u2010DA interpretation provides strong evidence of a disease\u2010specific metabolic pattern with dAMP, diiodothyronine, and 5\u2010methoxytryptophan as leading factors, and a sex\u2010specific metabolic pattern associated with orotidine 5\u2010phosphate, N\u2010acetylalanine, hydroxyproline, and cysteine. The results are verified using an independent sample set, which confirms the identification of specific signatures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>Metabolomics is used to identify low molecular weight molecular markers of PA, which paves the way for follow\u2010up validation studies in larger cohorts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.201800049","type":"journal-article","created":{"date-parts":[[2018,12,23]],"date-time":"2018-12-23T10:54:26Z","timestamp":1545562466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Urinary Metabolic Signature of Primary Aldosteronism: Gender and Subtype\u2010Specific Alterations"],"prefix":"10.1002","volume":"13","author":[{"given":"Alessandro","family":"Lana","sequence":"first","affiliation":[{"name":"Department of Ecological and Biological Sciences Tuscia University  01100 Viterbo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisha","family":"Alexander","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Genetics University of Colorado Denver Anschutz Medical Campus  80045 Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Castagna","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Internal Medicine University of Verona  37134 Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Genetics University of Colorado Denver Anschutz Medical Campus  80045 Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Morandini","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Internal Medicine University of Verona  37134 Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pizzolo","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Internal Medicine University of Verona  37134 Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zorzi","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Internal Medicine University of Verona  37134 Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Mulatero","sequence":"additional","affiliation":[{"name":"Department of Medicine and Experimental Oncology Division of Internal Medicine and Hypertension Unit University of Turin  10124 Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lello","family":"Zolla","sequence":"additional","affiliation":[{"name":"Department of Ecological and Biological Sciences Tuscia University  01100 Viterbo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8209-9056","authenticated-orcid":false,"given":"Oliviero","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Internal Medicine University of Verona  37134 Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,4]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.01.015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2805"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1295460"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02097"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3219"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2010.10.035"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000168"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb70538b"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073076"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0078"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032179"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.146613"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac401400b"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1411s37"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv380"},{"key":"e_1_2_7_18_1","first-page":"189","volume":"117","author":"McAnulty R. 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