{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:04Z","timestamp":1792802104468,"version":"4.5.0"},"reference-count":30,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pediatric Research Center, Helsinki University Hospital","id":[{"id":"https:\/\/ror.org\/02e8hzf44","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Finnish Foundation for Pediatric Research"},{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsan Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Swedish Childhood Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune endocrinopathy with severe and unpredictable course. The impact of APECED on mortality has not been determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess overall and cause-specific mortality of patients with APECED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Setting<\/jats:title>\n                    <jats:p>A follow-up study of Finnish patients with APECED from 1971 to 2018. Causes and dates of death were collected from Finnish registries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Ninety-one patients with APECED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measure<\/jats:title>\n                    <jats:p>Overall and cause-specific standardized mortality ratios (SMRs) determined by comparing the observed numbers of death and those expected on the basis of respective population death rates in Finland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall disease mortality was significantly increased (29 deaths, SMR 11; 95% confidence interval [CI] 7.2-16; P\u2005&amp;lt;\u20050.001). The relative risk (SMR) was highest in the youngest age groups but the absolute excess risk was similar (about 10 per 10\u2005000 person-years) in all age categories. The highest SMRs were seen for endocrine and metabolic diseases (SMR 570; 95% CI, 270-1000; P\u2005&amp;lt;\u20050.001) and for oral and esophageal malignancies (SMR 170; 95% CI, 68-360; P\u2005&amp;lt;\u20050.001). Mortality was also increased for infections, diseases of digestive system, alcohol-related deaths, and for accidents. Due to the small number of cases we were unable to evaluate whether mortality was affected by disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with APECED have significantly increased mortality in all age groups. Highest SMRs are found for causes that are directly related to APECED but also for infections. Increased alcohol- and accident-related deaths may be influenced by psychosocial factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa140","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T08:46:05Z","timestamp":1584521165000},"page":"e2207-e2213","source":"Crossref","is-referenced-by-count":46,"title":["Patients With APECED Have Increased Early Mortality Due to Endocrine Causes, Malignancies and infections"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8565-6364","authenticated-orcid":false,"given":"Joonatan","family":"Borchers","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-6440","authenticated-orcid":false,"given":"Eero","family":"Pukkala","sequence":"additional","affiliation":[{"name":"Faculty of Social Sciences, Tampere University, Tampere, Finland"},{"name":"Finnish Cancer Registry \u2013 Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-001X","authenticated-orcid":false,"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-7855","authenticated-orcid":false,"given":"Saila","family":"Laakso","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"issue":"4","key":"2021122105024121900_CIT0001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng1297-399","article-title":"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains","volume":"17","author":"Aaltonen","year":"1997","journal-title":"Nat Genet"},{"issue":"2","key":"2021122105024121900_CIT0002","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.4049\/jimmunol.178.2.1208","article-title":"A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"178","author":"Kek\u00e4l\u00e4inen","year":"2007","journal-title":"J Immunol."},{"issue":"7","key":"2021122105024121900_CIT0003","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1371\/journal.pmed.0030289","article-title":"Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1","volume":"3","author":"Meager","year":"2006","journal-title":"Plos Med."},{"issue":"2","key":"2021122105024121900_CIT0004","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1210\/jc.2003-030279","article-title":"Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I","volume":"89","author":"S\u00f6derbergh","year":"2004","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2021122105024121900_CIT0005","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1136\/jmg.29.11.824","article-title":"Polyglandular autoimmune syndrome type I among Iranian Jews","volume":"29","author":"Zlotogora","year":"1992","journal-title":"J Med Genet."},{"issue":"11","key":"2021122105024121900_CIT0006","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1515\/JPEM.2006.19.11.1343","article-title":"Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the Irish population","volume":"19","author":"Dominguez","year":"2006","journal-title":"J Pediatr Endocrinol Metab."},{"issue":"8","key":"2021122105024121900_CIT0007","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1210\/jc.2005-2611","article-title":"Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"91","author":"Perheentupa","year":"2006","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122105024121900_CIT0008","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1530\/EJE-07-0843","article-title":"Autoimmune polyendocrine syndrome type I in slovakia: Relevance of screening patients with autoimmune addison\u2019s disease","volume":"158","author":"F Magitta","year":"2008","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2021122105024121900_CIT0009","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1365-2796.2009.02090.x","article-title":"Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I","volume":"265","author":"Husebye","year":"2009","journal-title":"J Intern Med."},{"issue":"13","key":"2021122105024121900_CIT0010","doi-asserted-by":"crossref","first-page":"e88782","DOI":"10.1172\/jci.insight.88782","article-title":"Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"1","author":"Ferre","year":"2016","journal-title":"JCI Insight"},{"issue":"4","key":"2021122105024121900_CIT0011","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1210\/jc.2011-2461","article-title":"Autoimmune polyendocrine syndrome type 1: an extensive longitudinal study in Sardinian patients","volume":"97","author":"Meloni","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"8","key":"2021122105024121900_CIT0012","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1210\/jc.2016-1821","article-title":"A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1","volume":"101","author":"Bruserud","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122105024121900_CIT0013","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1530\/EC-17-0022","article-title":"Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study","volume":"6","author":"Zaidi","year":"2017","journal-title":"Endocr Connect."},{"issue":"9","key":"2021122105024121900_CIT0014","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1210\/jc.2017-00139","article-title":"Expanding the phenotypic and genotypic landscape of autoimmune polyendocrine syndrome type 1","volume":"102","author":"Orlova","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021122105024121900_CIT0015","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.oraloncology.2006.07.005","article-title":"Oral and oesophageal squamous cell carcinoma\u2013a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I)","volume":"43","author":"Rautemaa","year":"2007","journal-title":"Oral Oncol."},{"issue":"26","key":"2021122105024121900_CIT0016","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1056\/NEJM199006283222601","article-title":"Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients","volume":"322","author":"Ahonen","year":"1990","journal-title":"N Engl J Med."},{"issue":"5","key":"2021122105024121900_CIT0017","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1365-2265.2006.02495.x","article-title":"Bone health in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED): findings in 25 adults","volume":"64","author":"M\u00e4kitie","year":"2006","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2021122105024121900_CIT0018","volume-title":"Official statistics of Finland (OSF): Causes of death [e-publication]"},{"issue":"5","key":"2021122105024121900_CIT0019","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.jaad.2009.06.061","article-title":"Oral mucous squamous cell carcinoma-an anticipated consequence of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)","volume":"62","author":"B\u00f6ckle","year":"2010","journal-title":"J Am Acad Dermatol."},{"issue":"6","key":"2021122105024121900_CIT0020","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0002-9343(91)90215-J","article-title":"Frequent occurrence of asplenism and cholelithiasis in patients with autoimmune polyglandular disease type I","volume":"91","author":"Friedman","year":"1991","journal-title":"Am J Med."},{"issue":"6","key":"2021122105024121900_CIT0021","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1086\/302145","article-title":"A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1","volume":"63","author":"Pearce","year":"1998","journal-title":"Am J Hum Genet."},{"issue":"11","key":"2021122105024121900_CIT0022","doi-asserted-by":"crossref","first-page":"4396","DOI":"10.1073\/pnas.0809986106","article-title":"Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen","volume":"106","author":"Alimohammadi","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2021122105024121900_CIT0023","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev-immunol-032713-120222","article-title":"Anticytokine autoantibody-associated immunodeficiency","volume":"32","author":"Browne","year":"2014","journal-title":"Annu Rev Immunol."},{"issue":"1","key":"2021122105024121900_CIT0024","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/imr.12714","article-title":"Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"287","author":"Constantine","year":"2019","journal-title":"Immunol Rev."},{"issue":"1","key":"2021122105024121900_CIT0025","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/cen.12087","article-title":"What is the burden of living with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) in 2012? A health-related quality-of-life assessment in Finnish patients","volume":"79","author":"Kluger","year":"2013","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"12","key":"2021122105024121900_CIT0026","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1210\/jc.2006-0076","article-title":"Premature mortality in patients with Addison\u2019s disease: a population-based study","volume":"91","author":"Bergthorsdottir","year":"2006","journal-title":"J Clin Endocrinol Metab."},{"issue":"2-03","key":"2021122105024121900_CIT0027","first-page":"165","article-title":"An Update on Addison\u2019s Disease","volume":"127","author":"Barthel","year":"2019","journal-title":"Exp Clin Endocrinol Diabetes."},{"issue":"6","key":"2021122105024121900_CIT0028","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1210\/jc.2015-3908","article-title":"Epidemiology and diagnosis of hypoparathyroidism","volume":"101","author":"Clarke","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122105024121900_CIT0029","first-page":"127","article-title":"Biobanks and registers in epidemiologic research on cancer.","volume-title":"Methods in Molecular Biology","author":"Pukkala","year":"2011"},{"issue":"1-2","key":"2021122105024121900_CIT0030","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0379-0738(00)00300-5","article-title":"The validity of death certificates: routine validation of death certification and its effects on mortality statistics","volume":"115","author":"Lahti","year":"2001","journal-title":"Forensic Sci Int."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa140\/32924866\/dgaa140.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/6\/e2207\/41829495\/jcem_105_6_e2207.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/6\/e2207\/41829495\/jcem_105_6_e2207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:06:10Z","timestamp":1640045170000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/6\/e2207\/5809346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,18]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,3,18]]},"published-print":{"date-parts":[[2020,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa140","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6]]},"published":{"date-parts":[[2020,3,18]]}}}