Iron overload disorders

Abstract

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end‐organ damage. An elevated ferritin and transferrin‐iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate. A secondary cause for iron overload should be considered if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations. Differential diagnosis of secondary iron overload includes hematologic disorders, iatrogenic causes, or chronic liver diseases. More common hematologic disorders include thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency. If iron overload has been excluded, evaluation for causes of hyperferritinemia should be pursued. Causes of hyperferritinemia include chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, such as adult‐onset Still's disease or hemophagocytic lymphohistiocytosis. In this review, we describe the diagnostic testing of patients with suspected hereditary hemochromatosis, the evaluation of patients with elevated serum ferritin levels, and signs of secondary overload and treatment options for those with secondary iron overload.

Monitoring kidney size to interpret MRI‐based assessment of renal oxygenation in acute pathophysiological scenarios

“…To address this difference between our preclinical study and clinical reality, it is essential to obtain age, BMI, sex, and magnetic field strength corrected normal reference values for renal T 2 * and KS in healthy humans using standardized MRI protocols. A similar approach has been used for myocardial T 2 * mapping, which is now very well established for the quantitative assessment of tissue iron content and for the therapy of iron overload disorders 63–67 . It stands to reason that the normal reference values of renal T 2 * and KS can be deduced from large population imaging studies such as the German National Cohort or the UKBiobank 68,69 .…”

A critical evaluation of the role of iron overload in fatty liver disease

“…Patients with NASH have increased duodenal iron absorption through upregulated divalent metal iron transporter (DMT1) despite elevated hepcidin. 27 Subtle impairment in the ability of hepcidin to restrain iron absorption following an iron challenge suggests a hepcidin resistance state. 28 Dysbiosis can also result in increased gut permeability.…”

“…26 In addition, in NAFLD, iron export and regulation has been found to be impaired, with decreased hepatic hemojuvelin and ferroportin-1 expression, leading to hepatic iron retention. 27 The potential role of iron in progression of NAFLD to NASH. Iron overload is implicated as one of the "subsequent hits" in the multihit hypothesis that explains the progression from fatty liver to NASH and cirrhosis (Fig.…”

“…In brief, increased hepatic iron in DIOS may result from increased gut absorption and hepatic retention of iron. Patients with NASH have increased duodenal iron absorption through upregulated divalent metal iron transporter (DMT1) despite elevated hepcidin 27 . Subtle impairment in the ability of hepcidin to restrain iron absorption following an iron challenge suggests a hepcidin resistance state 28 .…”

“…In dysbiosis, there is increased production of proinflammatory cytokines such as interleukin‐22, which result in increased intestinal permeability 26 . In addition, in NAFLD, iron export and regulation has been found to be impaired, with decreased hepatic hemojuvelin and ferroportin‐1 expression, leading to hepatic iron retention 27 …”