Diagnostics: Markers of Body Iron Status

Iron is a micronutrient essential to nearly all living organisms. It plays a pleiotropic role in many vital metabolic processes beyond the classical function in hemoglobin synthesis. Both iron deficiency and iron overload are detrimental in humans, as iron excess can favor the generation of toxic oxygen radicals and cell death by ferroptosis. Therefore, an accurate assessment of iron status is paramount in many clinical settings. The classical biochemical parameters represented by serum ferritin and transferrin saturation (TSAT) are sufficiently informative in simple cases but do not work well whenever overt or subclinical inflammation is present, including acute diseases and many common chronic conditions (e.g., heart failure, dysmetabolic disorders, and chronic kidney disease). In these cases, they are neither sensitive nor specific enough to capture both iron deficiency and excess with sufficient accuracy. A typical controversy is represented by the ferritin thresholds to diagnose iron deficiency in different inflammatory disorders, which vary consistently in guidelines for specific diseases. To obtain meaningful information, clinicians can rely on the integration of additional indicators, including erythrocyte indices from automated analyzers, soluble transferrin receptor (sTfR), and hepcidin. The latter, however, are not universally available and often lack robust standardization. A further problem is represented by the difficulties in measuring non-transferrin-bound iron (NTBI), which plays a pivotal pathophysiological role in iron overload disorders. Herein, we provide a concise narrative overview of the available laboratory tools for the assessment of iron status, highlighting the current challenges and exploring the possible future solutions.