What are the clinical serum ferritin thresholds for diagnosing iron deficiency and iron overload in adults, including sex‑specific cut‑offs and adjustments for chronic inflammation?

Clinical Ferritin Thresholds

The American Gastroenterological Association recommends using a ferritin threshold of <45 ng/mL to diagnose iron deficiency in patients with anemia, which provides optimal sensitivity (85%) while maintaining acceptable specificity (92%). 1

Iron Deficiency Thresholds

Standard Population (Without Inflammation)

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency, making it the gold standard for definitively confirming depleted iron stores 1, 2
• Ferritin <30 μg/L generally indicates low body iron stores and warrants therapeutic intervention in most clinical scenarios 2, 3
• Ferritin <45 μg/L provides the optimal balance between sensitivity (85%) and specificity (92%) for clinical decision-making, particularly when evaluating patients for gastrointestinal investigation 1, 4

Adjusted Thresholds for Chronic Inflammation

In patients with inflammatory conditions (inflammatory bowel disease, chronic kidney disease, chronic heart failure), the ferritin threshold must be raised to <100 μg/L because ferritin is an acute-phase reactant that becomes falsely elevated during inflammation 2, 3

• Proinflammatory cytokines trigger hepcidin release, which sequesters iron in storage sites and restricts availability for erythropoiesis despite normal or elevated ferritin levels 3
• Transferrin saturation (TSAT) <20% confirms iron deficiency even when ferritin is elevated by inflammation 2, 3
• If ferritin is 100-300 μg/L in inflammatory conditions, TSAT <20% is required to confirm iron deficiency 3

Sex-Specific Considerations for Iron Overload

For hemochromatosis screening, the American Association for the Study of Liver Diseases uses sex-specific thresholds:

• Men: ferritin >300 μg/L suggests possible iron overload requiring further evaluation 1
• Women: ferritin >200 μg/L suggests possible iron overload requiring further evaluation 1
• These thresholds identified 88% of male and 57% of female C282Y homozygotes in the HEIRS study 1

Critical Algorithm for Interpretation

Step 1: Assess for Inflammation

• Check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) to determine if ferritin may be falsely elevated 2, 4
• If CRP/ESR are elevated, use the higher threshold of <100 μg/L for iron deficiency 2, 3

Step 2: Calculate Transferrin Saturation

• TSAT = (serum iron × 100) ÷ total iron-binding capacity 2, 4
• TSAT <16-20% confirms iron deficiency regardless of ferritin level 2, 4
• This is particularly critical when ferritin is in the borderline range (30-100 μg/L) 4, 3

Step 3: Apply Population-Specific Thresholds

For chronic kidney disease patients:

• Absolute iron deficiency: ferritin <100 ng/mL AND TSAT <20% 2, 4
• Functional iron deficiency: ferritin 100-700 ng/mL BUT TSAT <20% 2, 4

For general adult population:

• Ferritin <15 μg/L: absolute iron deficiency confirmed 1, 2
• Ferritin 15-30 μg/L: low iron stores, treatment warranted 2, 4
• Ferritin 30-45 μg/L: borderline; check TSAT to confirm 1, 4
• Ferritin 45-100 μg/L with inflammation: possible iron deficiency if TSAT <20% 2, 3

Common Pitfalls and Caveats

Never assume normal ferritin excludes iron deficiency in inflammatory states. Extreme cases have documented iron deficiency anemia with ferritin levels exceeding 26,000 μg/L in adult-onset Still's disease 5

• Research demonstrates that ferritin levels >50 μg/L can still be consistent with true iron deficiency when inflammation is present, with studies showing only 22% negative predictive value at this threshold 6
• The inflammatory ferritin is predominantly iron-free apoferritin, which explains why massive hyperferritinemia can coexist with severe iron depletion 5

Always measure TSAT alongside ferritin because ferritin alone provides an incomplete assessment of iron availability for erythropoiesis 2, 4, 7

• In chronic kidney disease patients, the scenario of ferritin >800 ng/mL with TSAT <20% has become increasingly common, representing functional iron deficiency despite apparent iron overload 7

For premenopausal women with iron deficiency, gastrointestinal investigation is conditional rather than mandatory unless red flags are present (age ≥50 years, GI symptoms, failure to respond to oral iron after 8-10 weeks, positive celiac or H. pylori testing) 1, 4