{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:43:38Z","timestamp":1790196218270,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n \n Hyperferritinemia is common in adults, yet most lack true iron overload. Confusion among metabolic, inflammatory, genetic, and reactive causes drives under\u2010investigation and over\u2010treatment, compounded by\n SGLT2<\/jats:styled-content>\n inhibitors and, less certainly,\n GLP<\/jats:styled-content>\n \u20101 receptor agonists. We synthesize the hepcidin\u2010ferroportin axis as the unifying mechanism and a transferrin saturation (\n TSAT<\/jats:styled-content>\n )\u2010guided pathway for workup.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Narrative review with structured\n PubMed<\/jats:styled-content>\n , Embase, and Cochrane searches through April 2026, written to address the\n SANRA<\/jats:styled-content>\n quality domains.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Ferritin above 10\u2009000\u2009\u03bcg\/L flags hemophagocytic lymphohistiocytosis (\n HLH<\/jats:styled-content>\n ), although the often\u2010cited 90%\/96% performance is pediatric; adult\n HLH<\/jats:styled-content>\n \u20102004 or\n HScore<\/jats:styled-content>\n \u2265\u2009169 reach 82%\u201395% sensitivity and 60%\u201394% specificity, lower in\n ICU<\/jats:styled-content>\n populations. The Valenti consensus on metabolic hyperferritinemia is partially validated against clinical outcomes in cohorts applying its grading. A\n TSAT<\/jats:styled-content>\n \u2010guided pathway directs workup toward\n HFE<\/jats:styled-content>\n genotyping, hepatic\n MRI<\/jats:styled-content>\n , or metabolic evaluation; soluble transferrin receptor (\n sTfR<\/jats:styled-content>\n ) and the\n sTfR<\/jats:styled-content>\n \/log\u2010ferritin index complement ferritin in distinguishing iron deficiency from anemia of inflammation, though\n sTfR<\/jats:styled-content>\n is itself influenced by inflammation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The hepcidin\u2010ferroportin axis unifies adult hyperferritinemia under\n TSAT<\/jats:styled-content>\n \u2010guided evaluation, though the algorithm does not capture diabetes risk in\n C282Y<\/jats:styled-content>\n homozygosity.\n SGLT2<\/jats:styled-content>\n inhibitors alter ferritin interpretation;\n GLP<\/jats:styled-content>\n \u20101 receptor agonists may do so, though dedicated human evidence remains insufficient. Both warrant documentation at review.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ejh.70285","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:31:36Z","timestamp":1786015896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperferritinemia: Pathophysiology, Etiologies, and Diagnostic Approach"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0889-4669","authenticated-orcid":false,"given":"Youjin","family":"Kim","sequence":"first","affiliation":[{"name":"Internal Medicine Legacy Health Vancouver Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1802-9673","authenticated-orcid":false,"given":"Thomas C.","family":"Landry","sequence":"additional","affiliation":[{"name":"Internal Medicine Legacy Health Vancouver Washington 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