Investigative algorithms for disorders affecting serum iron concentration: a narrative review

Background and Objective: Iron is an essential element to various processes within the human body. Abnormal serum iron levels can result from multiple aetiologies, some of which require further investigation to identify potentially serious underlying pathology. The article aims to aid the reader in diagnosing the underlying causes of serum iron derangement in humans. By the end of the article, the reader will be able to request and interpret appropriate investigations when managing a patient with low or high serum iron concentrations.

Methods: A narrative, focused literature review was performed using PubMed, MEDLINE, OMIM, and Google Scholar from January 2025 to March 2026 to identify references published from database inception to May 2026; reference lists from these articles were also used. Language was restricted to English.

Key Content and Findings: Iron is an essential element to various processes within the human body and is regulated by the peptide hepcidin. Disorders of iron homeostasis can result from disrupted absorption, storage, or regulation of iron. These factors are translated into abnormal biochemical markers including serum ferritin and transferrin saturation (TSAT). Potential causes include dietary intake, gastrointestinal disease, renal disease, liver disease, and genetic conditions. Algorithms are presented from a laboratory perspective to help identify common causes of abnormal iron status. Local guidelines should be used if available.

Conclusions: Diagnostic flow charts are presented focussing on high and low serum iron levels, and the limitations of laboratory tests discussed. These algorithms should help support healthcare professionals to efficiently and rapidly diagnose the common causes of abnormal iron states.