Albertine Donker

Standardized Pediatric Hepcidin Values 229 7 INTRODUCTION Hepcidin is a key regulatory hormone of systemic iron homeostasis by controlling iron absorption and bioavailability within the circulation. 1 In response to alterations in body iron demand, it is produced by hepatocytes and secreted into the circulation. It acts by binding the cellular iron exporter ferroportin, triggering its internalization and degradation, thereby inhibiting iron release from enterocytes and macrophages. 1 Hepdicin production is tightly regulated to prevent both iron deficit and iron overload. Its levels are decreased by hypoxia, erythropoietic activity and reduced levels of both circulating and stored body iron. 1 In contrast, its levels are increased by inflammation and infection as a host defense mechanism. By sequestering iron within the reticulo-endothelial system, plasma iron content is reduced and consequently limits extracellular microbial growth. 1,2 Dysregulation of hepcidin production contributes to the pathogenesis of several iron disorders. 2 Hepcidin is inappropriately low relative to stored iron in case of i) hereditary hemochromatosis 3 and ii) increased (especially ineffective) erythropoiesis 4 resulting in low hepcidin/ferritin ratios. 4 Conversely, hepcidin is inappropriately high relative to circulating transferrin bound iron in case of Iron Refractory Iron Deficiency Anemia (IRIDA) resulting in low TSAT/hepcidin ratios. 5,6 Hepcidin levels reflect the integration of multiple key signals involved in iron regulation. 7 Therefore, its measurement is a promising clinical tool for the diagnosis and management of iron disorders involving iron deficiency, iron loading and iron maldistribution. Examples include 1) evaluation of suspected IRIDA 5,6,8 ; 2) diagnosis of concomitant iron deficiency in patients with anemia of inflammation 9 ; 3) prediction of responsiveness to oral iron therapy and guiding iron treatment under conditions of competing signals (anemia, iron deficiency, inflammation) 10-12 ; 4) evaluation of suspected iron overload disorders 13 ; 5) evaluation of iron deficiency (ID), before the occurrence of iron deficiency anemia (IDA), for example in pregnant women 14,15 in children 16,17 and in children with cystic fibrosis. 18