Hepcidin response to acute iron intake and chronic iron loading in dysmetabolic iron overload syndrome

Authors

  • Paola Trombini,

    1. Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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  • Valentina Paolini,

    1. Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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  • Sara Pelucchi,

    1. Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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  • Raffaella Mariani,

    1. Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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  • Elizabeta Nemeth,

    1. Department of Medicine and Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • Tomas Ganz,

    1. Department of Medicine and Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • Alberto Piperno

    1. Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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Correspondence
Alberto Piperno, Department of Clinical Medicine and Prevention, Centre for Diagnosis and Therapy of Hemochromatosis, S.Gerardo Hospital, University of Milano-Bicocca, Via Pergolesi 33, 20052 Monza, Italy
Tel: +39 039 2339555
Fax: +39 039 322274
e-mail: alberto.piperno@unimib.it

Abstract

Background: The pathogenesis of dysmetabolic iron overload syndrome (DIOS) is still unclear. Hepcidin is the key regulator of iron homeostasis controlling iron absorption and macrophage release.

Aim: To investigate hepcidin regulation by iron in DIOS.

Methods: We analysed urinary hepcidin at baseline and 24 h after a 65 mg oral iron dose in 24 patients at diagnosis and after iron depletion (n=13) and compared data with those previously observed in 23 healthy controls. Serum iron indices, liver histology and metabolic data were available for all patients.

Results: At diagnosis, hepcidin values were significantly higher than in controls (P<0.001). After iron depletion, hepcidin levels decreased to normal values in all patients. At baseline, a significant response of hepcidin to iron challenge was observed only in the subgroup with lower basal hepcidin concentration (P=0.007). In iron-depleted patients, urinary hepcidin significantly increased after oral iron test (P=0.006).

Conclusions: Ours findings suggest that in DIOS, the progression of iron accumulation is counteracted by the increase in hepcidin production and progressive reduction of iron absorption, explaining why these patients develop a mild–moderate iron overload that tends to a plateau.

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