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.