#ROZE SIAH 87 FREE#
Within cells, limited amounts of free iron are found in a labile pool, which is biologically active in metabolism, although toxic if present in excess. This coordinated IRP1/IRE binding with respect to iron levels stabilizes cellular iron through the synthesis of ferritin. Both ribosomal subunits are now recruited to the mRNA and the translation of ferritin is activated. Upon high intracellular iron levels ( B), iron binds to IRP1, causing a transformational change that dissociates IRP1 from IRE. Upon low intracellular iron levels ( A), IRP1 binds to IRE, inhibiting the recruitment of the small ribosomal unit to mRNA, which results in a small ferritin pool. Schematic overview of regulated ferritin translation by the iron responsive element (IRE)/iron regulatory protein 1 (IRP1) system. Finally, we propose an algorithm for the further investigation and management of hyperferritinemia before general principles regarding the treatment of iron overload are addressed. Understanding of the fundamental aspects of iron metabolism and the mechanisms promoting elevations in ferritin levels is a prerequisite for rationally dealing with hyperferritinemia in clinical practice, and key points regarding this matter are therefore briefly presented below. In this overview, we discuss the biology, etiology, and clinical epidemiology of hyperferritinemia, based on a non-systematic selection of the literature, including international recommendations and guidelines and the authors’ own experiences. Based on the wide etiological spectrum, hyperferritinemia should prompt for further investigation through clinical examination and additional laboratory tests when the cause remains unknown. General practitioners seem somewhat unfamiliar with the appropriate management of hyperferritinemia, as >50% of primary care patients presenting with ferritin levels of such magnitude, and without any obvious clinical reason, are not referred to secondary care nor offered any further investigation. Subjects with a baseline ferritin ≥200 μg/L were found to have increased risk of cause-specific mortality due to cancer, endocrinological disease, and cardiovascular disease, as well as increased total mortality compared to those with levels 1000 μg/L is regarded as a non-specific marker of pathology. In a prospective Danish population-based study, ferritin proved to be a strong predictor of premature death in the general population. įerritin reference ranges may vary according to the analytical assay being used, although upper cut off is typically set to 200 μg/L in women and 300 μg/L in men. It may also be the result of increased synthesis and/or increased cellular secretion of ferritin upon various stimuli such as cytokines, oxidants, hypoxia, oncogenes, and growth factors. High ferritin, hyperferritinemia, may indicate increased iron stores, but is more commonly seen upon acute phase reactions and as a result of ferritin being released from damaged cells such as hepatocytes in liver disease. When concurrent inflammation is absent, ferritin has proven to be a highly specific and sensitive parameter for the diagnosis of iron deficiency. Ascribed to its proportionality to total body iron stores, ferritin function is an indirect marker of iron status.
Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed.įerritin is one of the most commonly requested laboratory tests in general and secondary care, and levels deviating from reference ranges are a frequent finding. We address the biology, etiology, and epidemiology of hyperferritinemia. In this review, we have performed a review of a selection of the literature based on the authors’ own experiences and assessments in accordance with international recommendations and guidelines. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency.
Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges.