{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:37:21Z","timestamp":1789141041981,"version":"build-2803163510"},"reference-count":29,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"The Foundation for Advanced Research in Hypertension and Cardiovascular Diseases"},{"name":"CORIS-Consorzio per la Ricerca Sanitaria","award":["ROSS_PRIV20_04"],"award-info":[{"award-number":["ROSS_PRIV20_04"]}]},{"name":"University of Padua DOR"},{"name":"DIMAR Excellence"},{"name":"Department of Medicine"},{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Double IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1\/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (\u03c72 = 22.492, P &amp;lt; .001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>NGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of patients with aldosterone-producing adenomas.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae411","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T11:13:09Z","timestamp":1718709189000},"page":"2433-2443","source":"Crossref","is-referenced-by-count":13,"title":["Double CYP11B1\/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism"],"prefix":"10.1210","volume":"109","author":[{"given":"Brasilina","family":"Caroccia","sequence":"first","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]},{"name":"Department of Women's and Children's Health-SBD, University of Padua , Padua 35122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-3015","authenticated-orcid":false,"given":"Livia","family":"Lenzini","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-8033","authenticated-orcid":false,"given":"Giulio","family":"Ceolotto","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gioco","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Benetti","sequence":"additional","affiliation":[{"name":"Division of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua , Padua 35122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Giannella","sequence":"additional","affiliation":[{"name":"Division of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua , Padua 35122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Ajjour","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Galuppini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgical Pathology Unit, University of Padua , Padua 35122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmaria","family":"Pennelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgical Pathology Unit, University of Padua , Padua 35122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-4086","authenticated-orcid":false,"given":"Teresa Maria","family":"Seccia","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"G.V. (Sonny) Montgomery VA Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center , Jackson, MS 39216 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-0931","authenticated-orcid":false,"given":"Gian Paolo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua , Padua 35126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"issue":"6018","key":"2025052704265054400_dgae411-B1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.1198785","article-title":"K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary 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