Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City

1 LetterOpen Access Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World’s Highest City Gaetano Cairo1 , Benoit Champigneulle2 , Margherita Correnti1 , Elena Gammella1 , Stefania Recalcati1 , Domenico Girelli3 , Annalisa Castagna3 , Anne-Kristine Meinild Lundby4 , Ivan Hancco2 , Carole Chirica5 , Dorra Guergour5 , Laura Oberholzer6 , Emeric Stauffer7,8 , Carsten Lundby9 , Aurélien Pichon10 , Julien V Brugniaux 2 , Stéphane Doutreleau2 , Samuel Verges 2 , Paul Robach2,11 Correspondence: Paul Robach (paul.robach@ensm.sports.gouv.fr). I ron is required for hemoglobin synthesis and red blood cell (RBC) production. When erythropoiesis is stimulated, erythroferrone, a hormone produced by erythroblasts in response to erythropoietin (EPO), downregulates hepcidin transcription in the liver. Lower hepcidin levels facilitate fer- roportin-mediated iron absorption in the duodenum and iron export from reticuloendothelial cells that process old/damaged RBCs, 1 thereby ensuring iron availability to the erythropoietic compartment. During acute high-altitude hypoxia, increased erythropoiesis results in iron mobilization, leading to decreased iron stores.2,3 By contrast, healthy permanent residents of alti- tudes of 3700–4380 m, chronically exposed to hypoxia, keep iron stores within the normal range, despite continuously high erythropoietic activity and iron demand. 4,5 Iron stores are also preserved in individuals living at 3825–4380 m who are affected by chronic mountain sickness (CMS),6,7 a clinical syndrome characterized by symptomatic excessive erythrocyto- sis and severe hypoxemia.8