{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:35:57Z","timestamp":1767897357862,"version":"3.49.0"},"reference-count":18,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011039","name":"Swiss Centre for Applied Human Toxicology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011039","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We describe two cases of hypertension and hypokalemia due to mineralocorticoid excess caused by posaconazole treatment of coccidioidomycosis and rhinocerebral mucormycosis infections, respectively. Clinical laboratory evaluations, including a comprehensive analysis of blood and urine steroid profiles, revealed low renin and aldosterone and indicated as the underlying mechanism primarily a block of 11\u03b2-hydroxylase activity in patient 1, whereas patient 2 displayed weaker 11\u03b2-hydroxylase but more pronounced 11\u03b2-hydroxysteroid dehydrogenase 2 inhibition. The results show that both previously suggested mechanisms must be considered and emphasize significant interindividual differences in the contribution of each enzyme to the observed mineralocorticoid excess phenotype. The mineralocorticoid symptoms of patient 1 resolved after replacement of posaconazole therapy by isavoconazole, and posaconazole dosage de-escalation ameliorated the effects in patient 2. By providing a thorough analysis of the patients\u2019 blood and urine steroid metabolites, this report adds further evidence for two individually pronounced mechanisms of posaconazole-induced hypertension and hypokalemia. The elucidation of the factors responsible for the individual phenotype warrants further research.<\/jats:p>","DOI":"10.1210\/js.2019-00189","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T09:44:05Z","timestamp":1562147045000},"page":"1361-1366","source":"Crossref","is-referenced-by-count":31,"title":["Posaconazole-Induced Hypertension Due to Inhibition of 11\u03b2-Hydroxylase and 11\u03b2-Hydroxysteroid Dehydrogenase 2"],"prefix":"10.1210","volume":"3","author":[{"suffix":"III","given":"George R","family":"Thompson","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases and the Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina R","family":"Beck","sequence":"additional","affiliation":[{"name":"Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Patt","sequence":"additional","affiliation":[{"name":"Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise V","family":"Kratschmar","sequence":"additional","affiliation":[{"name":"Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-2712","authenticated-orcid":false,"given":"Alex","family":"Odermatt","sequence":"additional","affiliation":[{"name":"Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"issue":"5","key":"2019070309425870600_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ckj\/sfx156","article-title":"Posaconazole-induced hypertension and hypokalemia due to inhibition of the 11\u03b2-hydroxylase enzyme","volume":"11","author":"Barton","year":"2018","journal-title":"Clin Kidney J"},{"issue":"1","key":"2019070309425870600_bib2","article-title":"Mineralocorticoid hypertension and hypokalaemia induced by posaconazole","volume":"2018","author":"Boughton","year":"2018","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"2019070309425870600_bib3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bcp.2017.01.010","article-title":"Inhibition of 11\u03b2-hydroxysteroid dehydrogenase 2 by the fungicides itraconazole and posaconazole","volume":"130","author":"Beck","year":"2017","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"2019070309425870600_bib4","doi-asserted-by":"crossref","first-page":"e02130-17","DOI":"10.1128\/AAC.02130-17","article-title":"Posaconazole-induced pseudohyperaldosteronism","volume":"62","author":"Kuriakose","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"8","key":"2019070309425870600_bib5","doi-asserted-by":"crossref","first-page":"e00760-17","DOI":"10.1128\/AAC.00760-17","article-title":"In vivo 11\u03b2-hydroxysteroid dehydrogenase inhibition in posaconazole-induced hypertension and hypokalemia","volume":"61","author":"Thompson","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2019070309425870600_bib6","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jsbmb.2018.10.016","article-title":"Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study","volume":"186","author":"Strajhar","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"15","key":"2019070309425870600_bib7","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1056\/NEJMcpc049016","article-title":"Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values","volume":"351","author":"Kratz","year":"2004","journal-title":"N Engl J Med"},{"key":"2019070309425870600_bib8","volume-title":"Endocrinology: Test Selection and Interpretation. The Quest Diagnostics Manual","author":"Nakamoto","year":"2012","edition":"Fifth Edition"},{"issue":"2","key":"2019070309425870600_bib9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0022-3476(97)70162-8","article-title":"Urinary phosphate\/creatinine, calcium\/creatinine, and magnesium\/creatinine ratios in a healthy pediatric population","volume":"131","author":"Matos","year":"1997","journal-title":"J Pediatr"},{"key":"2019070309425870600_bib10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.aca.2013.12.030","article-title":"Investigation of endogenous corticosteroids profiles in human urine based on liquid chromatography tandem mass spectrometry","volume":"812","author":"Marcos","year":"2014","journal-title":"Anal Chim Acta"},{"key":"2019070309425870600_bib11","unstructured":"MSD Merck Sharp & Dohme AG. NOXAFIL (posaconazole) prescribing information. Available at: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/022003s018s020,0205053s002s004,0205596s001s003lbl.pdf. Accessed June 27, 2019."},{"issue":"4","key":"2019070309425870600_bib12","doi-asserted-by":"crossref","first-page":"e00019-17","DOI":"10.1128\/AAC.00019-17","article-title":"Hypokalemia and hypertension associated with supratherapeutic posaconazole levels","volume":"61","author":"Mahmood","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"2019070309425870600_bib13","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1002\/pbc.25568","article-title":"Suspected posaconazole toxicity in a pediatric oncology patient","volume":"62","author":"Martino","year":"2015","journal-title":"Pediatr Blood Cancer"},{"issue":"7","key":"2019070309425870600_bib14","doi-asserted-by":"crossref","first-page":"e02605-17","DOI":"10.1128\/AAC.02605-17","article-title":"Refractory hypokalemia from syndrome of apparent mineralocorticoid excess on low-dose posaconazole","volume":"62","author":"Wassermann","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"2019070309425870600_bib15","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1592\/phco.26.12.1730","article-title":"Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants","volume":"26","author":"Saad","year":"2006","journal-title":"Pharmacotherapy"},{"issue":"5","key":"2019070309425870600_bib16","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.ejps.2004.01.005","article-title":"Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study","volume":"21","author":"Wexler","year":"2004","journal-title":"Eur J Pharm Sci"},{"issue":"2","key":"2019070309425870600_bib17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1124\/dmd.32.2.267","article-title":"Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil)","volume":"32","author":"Ghosal","year":"2004","journal-title":"Drug Metab Dispos"},{"issue":"6","key":"2019070309425870600_bib18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2165\/11319340-000000000-00000","article-title":"Pharmacokinetic\/pharmacodynamic profile of posaconazole","volume":"49","author":"Li","year":"2010","journal-title":"Clin Pharmacokinet"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/3\/7\/1361\/28900705\/js.2019-00189.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T20:37:23Z","timestamp":1569184643000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/3\/7\/1361\/5511566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,6]]},"references-count":18,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,6,6]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/js.2019-00189","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,6,6]]}}}