Review Article Integrative Food, Nutrition and Metabolism Integr Food Nutr Metab, 2019 doi: 10.15761/IFNM.1000241 Volume 6(1): 1-4 ISSN: 2056-8339 Diagnosis of hyperferritinemia in 2019 Khalid Serraj 1 *, Siham Hamaz 1 , Habiba Alaloui 1 , Houda Bachir 1 and Emmanuel Andrès 2 1 Internal Medicine Department, University Hospital of Oujda, Morocco 2 Internal Medicine Department, University Hospitals of Strasbourg, France Introduction Unlike hypoferritinemia, which almost constantly refects iron defciency, hyperferritinemia is ofen difcult to interpret in the absence of an obvious clinical context. In medical practice, major hyperferritinemia greater than 1000 μg/l is a classic situation. Moore et al. had published in 2013 the results of a 2-year study in a department of internal medicine that found a major hyperferritinemia in 627 patients with the most common causes of cancer [1]. Vardi et al. found similar results with a pejorative prognostic value of severe hyperferritinemia, regardless underlying cause [2]. Another much older study by Lee et al. found similar frequencies of hyperritinemia in the previous two studies with high frequency of etiological associations in the same patients [3]. Te high frequency of hyperferritinemia, their wide etiological spectrum and the frequent concomitant presence of several etiologies refect the need to address hyperferritinemia based on a global vision prioritizing the most obvious and serious causes. Iron metabolism and some defnitions according gen- der Hyperferritinemia is defned by serum values >400 μg/l in men and >300 μg/l in women. According to NHANES III, values generally found in the general population rarely exceed 200 μg/l in men and 150 μg/l in women. Furthermore, in a study by Murtagh et al. on patients with confrmed hereditary haemochromatosis, ferritin levels were between 300 and 3000 μg/l for men and between 250 and 3000 μg/l for women. Te interpretation of the limit values for ferritinemia must therefore be extremely cautious, especially in the absence of a plausible condition explaining these values. A ferritinemia between 300 and 400 μg/l in men and between 200 and 300 μg/l in women can be synonymous with a real overload martial imposing a close biological monitoring or a thorough assessment from the outset. On the other hand, a ferritinemia less than 100 μg/l in an infammatory context or any other hyperferritinemic situation should be considered a potential iron defciency and managed as such [4,5]. A small amount of exogenous iron not exceeding 2 mg/day is absorbed by the duodenum and partially stored in the enterocytes as ferritin. Most of the body's iron comes from a recycling phenomenon *Correspondence to: Khalid Serraj, Internal Medicine Department, University Hospital of Oujda, Morocco, E-mail: serrajkhalid@yahoo.fr Key words: ferritin, hemochromatosis, infammation, cytolysis, metabolic syndrome, alcohol Received: December 21, 2018; Accepted: January 14, 2019; Published: January 17, 2019 Abstract Although hyperferritinemia is not specifc, it may be diagnostically very contributing if well interpreted by the physician. Physiologically, ferritin is a protein synthesized essentially by the liver and intended to store iron in the liver, macrophage and erythrocyte. Despite this, the increase in ferritinemia does not necessarily mean iron overload or liver disease. A global approach integrating the degree of ferritinemia, anamnesis and clinical context makes possible in the vast majority of cases to fnd the cause of hyperferritinemia without going through the saturation factor of transferrin and thorough liver investigations. Te use of transferrin saturation coefcient, liver imaging, genetic tests or even liver biopsy proves to be necessary only in rare cases where the most obvious causes could not be identifed. through macrophages that provide physiological hemolysis and degradation of senescent hemoglobin. Tis iron is subsequently transported to the bone marrow at a rate of 20 mg per day but also and especially to the hepatocytes which are the main storage site for ferritin. Excretion is through enterocytes and menstruation. Ferritin is a protein synthesized by the liver in the form of an egg about 12 nm in diameter able to store up to 5000 iron atoms. It is present mainly in hepatocytes, macrophages and cells of the red line but remains extremely ubiquitous topographically and functionally, which explains its elevation in several etiologies including hepatopathies, infammation and cytolysis in addition to overload martial [6]. Main causes of hyperferritinemia Hereditary hemochromatosis Te absorption of dietary iron is done by the enterocyte through the carriers "DMT1" and "Ferroportin". Subsequently, passage through the circulation, transferrin binding and interaction with the transferrin receptor (TFR) of the cryptic cell and the hepatic HFE protein occur. Ferroportin is also present on the surface of the macrophage. In the healthy person, there is a sufcient production of hepcidin which has as a function the negative regulation of the activity of DMT1 and ferroportin and therefore the limitation of the passage of iron in the blood from the enterocyte and macrophage. In the person with HFE mutation, there are 3 essential abnormalities: 1) Alteration of the HFE-TFR interaction resulting in less iron entry into the cryptic cell and the emission of a false defciency signal resulting in an absorptive response of iron; 2) A release of enterocyte iron to the plasma by hyperactivity DMT1 and ferroportin; 3) A release of macrophagic iron by hyperactivity of macrophagic ferroportin. Te consequence of these