Iron Overload: Pathophysiology, Diagnosis and Monitoring

Iron overload is associated with significant health risks, underscoring the importance of understanding its pathophysiology as well as establishing accurate diagnostic and monitoring methods. Chronic iron overload is associated with either genetic disorders characterized by excessive iron accumulation (hereditary hemochromatosis), or is secondary to diseases of ineffective erythropoiesis and/or requiring regular blood transfusions (like thalassemia, sickle cell disease, myelodysplastic syndromes). Diagnosis is based on clinical suspicion, corroborated by laboratory findings such as elevated serum ferritin and transferrin saturation, along with imaging techniques (magnetic resonance imaging) which facilitate non-invasive assessment of iron levels in parenchymal organs. Elevated ferritin and transferrin saturation and exclusion of secondary causes should prompt genetic evaluation for hereditary disorders predisposing iron overload. Chronic systemic iron overload causes progressive tissue iron accumulation, leading to severe clinical implications, including myocardial dysfunction, liver cirrhosis, and increased risk of hepatocellular carcinoma. Monitoring includes evaluating iron overload indices (serum ferritin, transferrin saturation, liver and heart iron concentration) along with serum and urine indices of parenchymal organ damage at different timepoints regarding the type of disease, patient's age, severity and response to treatment, and aims in improving disease progression and preventing complications. This article provides a comprehensive overview of the pathophysiologic mechanisms and the diagnostic and monitoring techniques of iron overload, in order to revise current knowledge and to raise clinical awareness for effective management.