{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:31Z","timestamp":1792687171026,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Primary adrenal insufficiency (PAI) is commonly caused by autoimmunity in adults, known as autoimmune Addison\u2019s disease (AAD). Autoantibodies against 21-hydroxylase are a hallmark of AAD but are absent in some patients diagnosed with AAD, posing a challenge to their clinical management.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We tested a polygenic risk score for AAD (PRS14\n                    <jats:sub>AAD<\/jats:sub>\n                    ) to prioritize seronegative patients for etiologic reevaluation. The PRS14\n                    <jats:sub>AAD<\/jats:sub>\n                    was calculated in patients diagnosed with AAD but lacking 21-hydroxylase autoantibodies (\n                    <jats:italic>n<\/jats:italic>\n                    = 124). Patients with low (\n                    <jats:italic>n<\/jats:italic>\n                    = 35) or high (\n                    <jats:italic>n<\/jats:italic>\n                    = 10) genetic susceptibility to AAD underwent clinical re-evaluation and whole-genome sequencing.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Of the 34 patients with low PRS14\n                    <jats:sub>AAD<\/jats:sub>\n                    , 14 (41%) were re-diagnosed with non-autoimmune adrenal insufficiency, whereas no alternative etiologies were identified in patients with high PRS14\n                    <jats:sub>AAD<\/jats:sub>\n                    . The low PRS group included six patients (17%) with confirmed monogenic PAI and eight patients (23%) with adrenal insufficiency due to either tuberculosis or non-primary causes. Notably, four of the six confirmed monogenic cases developed PAI in adulthood, consistent with late-onset disease caused by hypomorphic variants. Additionally, seven patients (20%) carried genetic variants suspected of causing monogenic disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    These findings support considering genetic evaluation in patients with seronegative PAI, regardless of the age at diagnosis.\n                  <\/jats:p>","DOI":"10.1172\/jci206184","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:17Z","timestamp":1792684817000},"source":"Crossref","is-referenced-by-count":0,"title":["Polygenic risk score identifies alternative etiologies in misdiagnosed cases of primary adrenal insufficiency"],"prefix":"10.1172","author":[{"given":"Maribel","family":"Aranda-Guill\u00e9n","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana Ruxandra","family":"Botusan","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venuja","family":"Fernando","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Barbaro","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Blomqvist","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen Christine","family":"R\u00f8yrvik","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-2248","authenticated-orcid":true,"given":"Anette Susanne B\u00f8e","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eystein Sverre","family":"Husebye","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kemp","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2612-6301","authenticated-orcid":true,"given":"Anna","family":"Wedell","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4506-9955","authenticated-orcid":true,"given":"Olov","family":"Ekwall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Isaksson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Wahlberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Lindgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Skov","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhildur","family":"Bergthorsdottir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Dahlqvist","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-2860","authenticated-orcid":true,"given":"Sophie","family":"Bensing","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"K\u00e4mpe","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/206184\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:18Z","timestamp":1792684818000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/206184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"alternative-id":["10.1172\/JCI206184"],"URL":"https:\/\/doi.org\/10.1172\/jci206184","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}