What is the difference between serum iron and ferritin (Ferritin) in diagnosing iron deficiency?

Difference Between Serum Iron and Ferritin in Diagnosing Iron Deficiency

Serum ferritin reflects iron storage levels in the body, while serum iron measures circulating iron that is immediately available for use; ferritin is the more reliable indicator for diagnosing iron deficiency but can be falsely elevated during inflammation. 1, 2

Key Differences Between Serum Iron and Ferritin

Serum Iron

• Measures the amount of iron bound to transferrin in the bloodstream 2
• Represents iron that is currently in transit and available for immediate use in erythropoiesis 2
• Used to calculate Transferrin Saturation (TSAT) by the formula: (serum iron × 100) ÷ TIBC 1
• Shows diurnal variation, which may affect interpretation if not collected at consistent times 1
• Reflects readily available iron but not total body iron stores 1

Serum Ferritin

• Reflects storage iron contained within liver, spleen, and bone marrow reticuloendothelial cells 1
• Serves as the most specific indicator available of depleted iron stores 2
• Has a direct relationship with stored iron: 1 μg/L of serum ferritin equals approximately 10 mg of stored iron 2
• Acts as an acute-phase reactant, increasing during inflammation independent of iron status 1, 2
• Normal values vary by population: 135 μg/L for men, 43 μg/L for women, and approximately 30 μg/L for children aged 6-24 months 2

Diagnostic Value in Iron Deficiency

Using Serum Iron

• Less reliable as a standalone test due to diurnal variation 1
• More valuable when used to calculate TSAT 1
• TSAT < 20% traditionally indicates iron deficiency, though this is not perfectly accurate 1
• TSAT reflects iron readily available for erythropoiesis rather than total body stores 1

Using Ferritin

• Most specific indicator of depleted iron stores 2
• Serum ferritin < 15 μg/L is highly specific for iron deficiency (specificity 0.99) 2
• Levels < 30 μg/L generally indicate low body iron stores 2
• Values > 150 μg/L rarely occur with absolute iron deficiency, even with inflammation 2
• In chronic kidney disease patients, absolute iron deficiency is defined as ferritin < 100 ng/mL and TSAT < 20% 1

Clinical Pitfalls and Caveats

Inflammation Effect

• Ferritin is an acute-phase reactant that increases during inflammation, potentially masking iron deficiency 1, 2
• In patients with inflammation, iron deficiency may be present with ferritin levels up to 50-100 μg/L 2
• When inflammation is present, a sudden increase in ferritin with a drop in TSAT suggests inflammatory iron block rather than true iron sufficiency 1

Functional vs. Absolute Iron Deficiency

• Absolute iron deficiency: depleted iron stores (low ferritin) with impaired iron delivery (low TSAT) 1
• Functional iron deficiency: normal or elevated ferritin but insufficient iron release to meet demands, resulting in low TSAT 1
• Distinguishing between functional iron deficiency and inflammatory iron block is a common clinical challenge, as both can present with TSAT < 20% and ferritin 100-700 ng/mL 1

Optimizing Diagnostic Accuracy

• Neither serum iron nor ferritin alone provides a complete picture of iron status - they should be interpreted together 2
• Consider clinical context and other markers when interpreting results 2
• Recent evidence suggests that current ferritin reference ranges may lead to underdiagnosis of iron deficiency, particularly in women 3
• Some experts recommend maintaining serum ferritin between 65-160 ng/mL in dialysis patients to avoid both iron deficiency and overload 4