{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:36:48Z","timestamp":1791041808261,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"DOI":"10.13039\/501100001659","name":"the Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["Projektnummer: 314061271 - TRR 205"],"award-info":[{"award-number":["Projektnummer: 314061271 - TRR 205"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Else Kr\u00f6ner-Fresenius Stiftung","award":["2015_A171"],"award-info":[{"award-number":["2015_A171"]}]},{"name":"the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme","award":["No [694913]"],"award-info":[{"award-number":["No [694913]"]}]},{"name":"he National Institute of General Medical Sciences grant U54","award":["GM115428"],"award-info":[{"award-number":["GM115428"]}]},{"DOI":"10.13039\/501100008426","name":"Friedrich Baur Stiftung","doi-asserted-by":"crossref","award":["grant number 46\/16"],"award-info":[{"award-number":["grant number 46\/16"]}],"id":[{"id":"10.13039\/501100008426","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,5]]},"abstract":"<jats:p>\n                    Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption\/ionization\u2013Fourier transform\u2013ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype\/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    - and\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    -mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.130356","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T11:01:02Z","timestamp":1567594862000},"source":"Crossref","is-referenced-by-count":45,"title":["In situ metabolomics of aldosterone-producing adenomas"],"prefix":"10.1172","volume":"4","author":[{"given":"Masanori","family":"Murakami","sequence":"first","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara","family":"Rhayem","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kunzke","sequence":"additional","affiliation":[{"name":"Research Unit Analytical Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Unit Analytical Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Feuchtinger","sequence":"additional","affiliation":[{"name":"Research Unit Analytical Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim Matthias","family":"Strom","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany."},{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-2082","authenticated-orcid":true,"given":"Celso","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, G.V. 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