{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:57:14Z","timestamp":1753891034196,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Suomen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","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\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsanin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Hypokalemia is a common finding in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) but its exact cause often remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the prevalence and etiology of hypokalemia and the role of adrenal steroids therein in a cohort of patients with APECED.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a cross-sectional assessment and retrospective data collection on 44 Finnish patients with APECED to identify subjects with episodes of hypokalemia. Also 68 healthy matched controls attended the cross-sectional evaluation. Factors associating with a tendency for hypokalemia were analyzed by reviewing medical records during 1960-2021 and performing a cross-sectional analysis of serum adrenal steroids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total 14 of the 44 APECED patients (32%) had episodes of hypokalemia; 2 presented with hypokalemia at cross-sectional evaluation and 12 had a history of hypokalemia before the cross-sectional evaluation. Hypokalemic episodes started at the median age of 14.1 years; 12\/14 (86%) had primary adrenal insufficiency (PAI). The median number of hypokalemic periods per year was 0.3 (range 0.04-2.2); the frequency correlated positively with the number of clinical APECED manifestations at the time of cross-sectional evaluation (r=0.811, p&amp;lt;0.001). Etiologies of hypokalemia varied but episodes often occurred when new clinical manifestations developed and during hospitalizations. Three patients had kidney defects, also associated with electrolyte imbalances. Severity of hypokalemia varied (range 2.2-3.2 mmol\/L), but no severe complications were observed. At cross-sectional evaluation, patients with PAI (n = 30) had significantly lower median plasma potassium and higher sodium concentration than controls, suggesting that fludrocortisone treatment contributed to hypokalemia. Detailed analysis of adrenal steroids provided no conclusive differences between patients with and without episodes of hypokalemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In APECED, hypokalemia is common and varies in terms of frequency, etiology, and severity. PAI and kidney disease predispose to hypokalemia. In addition, hypokalemic periods seem to be more common in patients with more severe phenotype of APECED.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.904507","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:46:17Z","timestamp":1655873177000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Recurrent Hypokalemia and Adrenal Steroids in Patients With APECED"],"prefix":"10.3389","volume":"13","author":[{"given":"Joonatan","family":"Borchers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarmo","family":"J\u00e4\u00e4skel\u00e4inen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saila","family":"Laakso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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"},{"key":"B2","doi-asserted-by":"publisher","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"},{"key":"B3","doi-asserted-by":"publisher","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"},{"key":"B4","doi-asserted-by":"publisher","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"},{"key":"B5","doi-asserted-by":"publisher","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"},{"key":"B6","doi-asserted-by":"publisher","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"},{"key":"B7","doi-asserted-by":"publisher","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"},{"key":"B8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13256-021-02724-6","article-title":"Addison's Disease Associated With Hypokalemia: A Case Report","volume":"15","author":"Abdalla","year":"2021","journal-title":"J Med Case Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00109","article-title":"Severe Phenotype of APECED (APS1) Increases Risk for Structural Bone Alterations","volume":"11","author":"Laakso","year":"2020","journal-title":"Front Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.784195","article-title":"Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1)","volume":"12","author":"Saari","year":"2021","journal-title":"Front Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2522","article-title":"Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study","volume":"102","author":"Dalin","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-97-3-370","article-title":"Ketoconazole Blocks Adrenal Steroid Synthesis","volume":"97","author":"Pont","year":"1982","journal-title":"Ann Intern Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci110903","article-title":"Ketoconazole Blocks Adrenal Steroidogenesis by Inhibiting Cytochrome P450-Dependent Enzymes","volume":"71","author":"Loose","year":"1983","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(87)91014-2","article-title":"Mineralocorticoid Activity of Liquorice: 11-Beta-Hydroxysteroid Dehydrogenase Deficiency Comes of Age","volume":"2","author":"Stewart","year":"1987","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70142-1","article-title":"Diagnosis and Management of Adrenal Insufficiency","volume":"3","author":"Bancos","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.75.1.1320051","article-title":"Diagnosis and Therapy Surveillance in Addison's Disease: Rapid Adrenocorticotropin (ACTH) Test and Measurement of Plasma ACTH, Renin Activity, and Aldosterone","volume":"75","author":"Oelkers","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline","volume":"101","author":"Bornstein","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31827356e1","article-title":"Gastrointestinal Manifestations in APECED Syndrome","volume":"47","author":"Kluger","year":"2013","journal-title":"J Clin Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-016-3394-5","article-title":"Tubulointerstitial Nephritis: Diagnosis, Treatment, and Monitoring","volume":"32","author":"Joyce","year":"2017","journal-title":"Pediatr Nephrol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003993","article-title":"Long-Term Outcome of Kidney Transplantation in 6 Patients With Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)","volume":"106","author":"Laakso","year":"2021","journal-title":"Transplantation"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-015-3083-9","article-title":"Clinical and Laboratory Approaches in the Diagnosis of Renal Tubular Acidosis","volume":"30","author":"Santos","year":"2015","journal-title":"Pediatr Nephrol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-49-5-757","article-title":"A Syndrome of Apparent Mineralocorticoid Excess Associated With Defects in the Peripheral Metabolism of Cortisol","volume":"49","author":"Ulick","year":"1979","journal-title":"J Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz315","article-title":"Classic and Nonclassic Apparent Mineralocorticoid Excess Syndrome","volume":"105","author":"Carvajal","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1780","article-title":"Dehydroepiandrosterone Sulfate in the Assessment of the Hypothalamic-Pituitary-Adrenal Axis","volume":"93","author":"Fischli","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12730","article-title":"What is the Optimal Bone-Preserving Strategy for Patients With Addison's Disease","volume":"83","author":"Lee","year":"2015","journal-title":"Clin Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.904507\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:46:21Z","timestamp":1655873181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.904507\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":25,"alternative-id":["10.3389\/fendo.2022.904507"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.904507","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"article-number":"904507"}}