A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis

Domenico Girelli, Paola Trombini, Fabiana Busti, Natascia Campostrini, Marco Sandri, Sara Pelucchi, Mark Westerman, Tomas Ganz, Elizabeta Nemeth, Alberto Piperno, Clara Camaschella

Research output: Contribution to journalArticlepeer-review


Background: Inadequate hepcidin production leads to iron overload in nearly all types of hemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFE-hemochromatosis, in two with TFR2-hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6 C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after phlebotomy-induced normalization of iron stores. Design and Methods: We analyzed serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron. Results: Serum iron and transferrin saturation significantly increased at 4 hours and returned to baseline values at 8-12 hours in all groups, except in the iron-normalized patients who showed the highest and longest increase of both parameters. The level of hepcidin increased significantly at 4 hours and returned to baseline at 24 hours in controls and in the C282Y/H63D compound het-erozygotes at diagnosis. The hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in the patients with iron-depleted HFE-hemochromatosis and absent in those with TFR2-hemochromatosis. Conclusions: Our results are consistent with a scenario in which TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.

Original languageEnglish
Pages (from-to)500-506
Number of pages7
Issue number4
Publication statusPublished - Apr 2011


  • Hemochromatosis
  • Hepcidin
  • Iron challenge
  • Phlebotomy
  • Transferrin receptor 2

ASJC Scopus subject areas

  • Hematology


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