[Iron's ups and downs]

Iron is an essential trace metal whose extracellular concentration and stores are efficiently regulated. Systemic iron homeostasis assures a stable milieu in which each cell regulates its iron uptake to meet its own requirements. The system is challenged by variable availability of iron in the diet, by occasional iron losses through bleeding and by the fluctuations in the iron request by iron requiring processes such as erythropoiesis, growth, pregnancy and lactation; but also by pathologic processes involving aberrant iron retention leading to tissue iron overload and finally to end organ damage. A low serum ferritin is 100% specific for iron deficiency ; conversely hyperferritinemia is not a reliable sign of iron overload. Iron deficiency is a pan-ethnic disorder more prevalent in western and ageing people. Anemia represents the end stage of iron deficiency. During inflammatory states, iron becomes unavailable for erythropoiesis although adequate stores are present. This phenomenon is called functional iron deficiency and is characteristic of anemia of chronic disorders. Hyperferritinemia may exist in the presence or in the absence of iron overload. A cut off value of > 45% for transferrine saturation has been suggested to discriminate both settings. All the acquired conditions associated with hyperferritinemia must be excluded before performing genetic testing. Perfect understanding of iron homeostasis regulation as well as an adequate use of analyses exploring iron metabolism are mandatory for proper clinical management of iron deficiency and overload states.