{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:42:45Z","timestamp":1791916965409,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement \u2265 5000 \u00b5g\/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 \u00b5g\/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels &gt; 10,000 \u00b5g\/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels &gt; 15,000 \u00b5g\/L. Extreme hyperferritinemia (TSF levels &gt; 25,000 \u00b5g\/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 \u03bcg\/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.<\/jats:p>","DOI":"10.3390\/jcm11185438","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T02:06:50Z","timestamp":1663553210000},"page":"5438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Extreme Hyperferritinemia: Causes and Prognosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-8970","authenticated-orcid":false,"given":"Maxime","family":"Fauter","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Lyon 1 University, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4564-2931","authenticated-orcid":false,"given":"Sabine","family":"Mainbourg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Vascular Pathology, University Hospital Lyon Sud, Lyon 1 University, 69000 Lyon, France"},{"name":"Laboratoire de Biom\u00e9trie et Biologie Evolutive, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, CNRS, UMR 5558, 69622 Villeurbanne, France"},{"name":"LIFE, Lyon Immunology Federation, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"El Jammal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Guerber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Zaepfel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University Hospital Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-8565","authenticated-orcid":false,"given":"Thomas","family":"Henry","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Lyon 1 University, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4245-8039","authenticated-orcid":false,"given":"Mathieu","family":"Gerfaud-Valentin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-3842","authenticated-orcid":false,"given":"Pascal","family":"S\u00e8ve","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"},{"name":"Research on Healthcare Performance (RESHAPE), INSERM U1290, Lyon 1 University, 69373 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-3650","authenticated-orcid":false,"given":"Yvan","family":"Jamilloux","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Croix-Rousse, Lyon 1 University, 69004 Lyon, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Lyon 1 University, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"},{"name":"LIFE, Lyon Immunology Federation, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/bjh.15166","article-title":"Investigation and management of a raised serum ferritin","volume":"181","author":"Cullis","year":"2018","journal-title":"Br. 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