Hepcidin in the diagnosis of iron disorders

Abstract

The discovery of the iron-regulatory hormone hepcidin in 2001 has revolutionized our understanding of iron disorders, and its measurement should advance diagnosis/treatment of these conditions. Although several assays have been developed, a gold standard is still lacking, and efforts toward harmonization are ongoing. Nevertheless, promising applications can already be glimpsed, ranging from the use of hepcidin levels for diagnosing iron-refractory iron deficiency anemia to global health applications such as guiding safe iron supplementation in developing countries with high infection burden.

Modern iron replacement therapy: clinical and pathophysiological insights

“…The regulation of hepcidin and ferroportin expression at molecular level is quite complex, and its description is beyond the scope of this article (for comprehensive reviews see [22][23][24]). From a clinical standpoint, hepcidin production is modulated by a number of physiological and pathological conditions that can exert opposite influences [25]. The three major determinants are body iron stores, erythropoietic activity, and inflammation [24] (Fig.…”

“…Nevertheless, serum hepcidin levels reflect the balance of multiple opposing influence [25], and exception to this rule can be due to genetic or acquired conditions. Subjects homozygous for mutations in TMPRSS6, encoding the hepcidin inhibitor Matriptase-2, are affected by a rare genetic form of anemia named Iron Refractory Iron Deficiency Anemia (IRIDA, OMIM #206200) [64].…”

“…This condition should be suspected in patients presenting with IDA early in life, and poor or no response to oral iron without apparent cause [65,66]. Indeed, the biochemical hallmark of IRIDA is the presence of high (or inappropriately normal) serum hepcidin levels [25], which are pathogenetically relevant. Relatively high or inappropriately normal hepcidin levels can be found also in ID patients with a concomitant inflammatory disorder [67,68].…”

“…The same concept was previously suggested by two retrospective studies in cancer patients [77], and in unselected IDA patients [78], where baseline hepcidin levels predicted subsequent responsiveness to oral iron. After initial technical difficulties, hepcidin assays are continuously improving, and a number of them showing good accuracy and reproducibility have been internationally validated [25]. However, lack of harmonization (i.e.…”

The usefulness of routinely used malnutrition screening tools in predicting anemia in lung cancer patients

“…7 Despite the many factors leading to the development of CRA, it is believed that the influence of the inflammatory process is one of the key components of its pathomechanism. 12,13 The main impact of proinflammatory cytokines in CRA is the disruption in Fe metabolism. Proinflammatory mediators increase hepcidin expression, which blocks Fe flows into plasma, with the resulting effect of the unavailability of Fe for erythropoiesis.…”