What blood tests diagnose iron deficiency versus iron overload and how are results interpreted?
Executive summary
Iron status is diagnosed by a panel of blood tests — commonly serum ferritin, serum iron, total iron‑binding capacity (TIBC) or transferrin, and transferrin saturation — interpreted together because each marker has limits and is influenced by inflammation, liver disease and other conditions [1] [2]. Low ferritin and low transferrin saturation with high TIBC point to iron deficiency, while high ferritin and high transferrin saturation suggest iron overload, but definitive assessment sometimes requires genetic testing or imaging for organ iron [3] [4] [5].
1. What the core tests measure and why they matter
Serum ferritin measures stored iron and is the most specific routine test for assessing iron stores: low ferritin reliably indicates iron deficiency, whereas high ferritin raises suspicion for iron overload — though ferritin is also an acute‑phase reactant that rises with inflammation, infection or liver disease and must be interpreted in context [2] [3]. Serum iron reports circulating iron bound to transferrin but fluctuates with diet and diurnal variation and is therefore less reliable alone; clinicians use it alongside TIBC/transferrin and ferritin to build a picture [6] [7].
2. TIBC, transferrin saturation and the key ratios clinicians use
Total iron‑binding capacity (TIBC) or transferrin concentration reflects the blood’s capacity to carry iron; TIBC rises in uncomplicated iron deficiency and falls in inflammatory states or protein‑loss conditions, so a pattern of low serum iron, high TIBC (or transferrin) and low transferrin saturation supports iron deficiency [8] [7]. Transferrin saturation — calculated as serum iron divided by TIBC — is a practical discriminator: saturation <15% generally indicates iron deficiency, while elevated saturation flags possible hereditary hemochromatosis or transfusional iron overload [9] [7].
3. How patterns map to diagnoses: iron deficiency vs iron overload
Classic iron deficiency: low hemoglobin if anemia is present, low serum iron, low ferritin, high TIBC/transferrin and low transferrin saturation — this constellation confirms depleted iron stores and guides treatment [10] [7]. Classic iron overload: elevated transferrin saturation often appears early (especially in HFE‑related hemochromatosis), with rising ferritin (men >300 ng/mL and women >150–200 ng/mL raise concern) and organ iron deposition; serum iron alone is insufficient to diagnose chronic overload [4] [5].
4. When tests can mislead and what to do about it
Inflammation, chronic disease and liver injury can elevate ferritin and lower TIBC, masking iron deficiency (functional iron deficiency) and producing misleading profiles; in such cases soluble transferrin receptor, CRP to document inflammation, repeat testing, or bone marrow/functional assessments may be needed because single tests can be inconclusive [2] [10]. Conversely, isolated high ferritin without high transferrin saturation can reflect inflammation, metabolic syndrome, or liver disease rather than true overload, so genetic testing (HFE) and organ imaging (MRI quantifying liver iron) are recommended when biochemical testing suggests overload [4] [5].
5. Practical interpretation and the clinical workflow
Laboratories report reference ranges that vary and clinicians always interpret values against symptoms, CBC results (to confirm anemia), and other labs; an “iron panel” — serum iron, TIBC/transferrin, transferrin saturation and ferritin — is the standard starting point, with escalation to inflammatory markers, soluble transferrin receptor, genetic tests or imaging when patterns are inconsistent or when organ damage is suspected [1] [6] [4]. For suspected hereditary hemochromatosis clinicians commonly follow transferrin saturation and ferritin, then order HFE mutation testing and, if indicated, liver imaging or biopsy to assess tissue iron and damage [5] [4].