What is the ferritin level cut-off for iron deficiency in adults?

Ferritin Cut-off for Iron Deficiency in Adults

Direct Answer

Use a ferritin cut-off of <45 μg/L to diagnose iron deficiency in clinical practice, as this provides the optimal balance between sensitivity and specificity (92% specificity) for detecting iron deficiency. 1

Ferritin Thresholds Based on Clinical Context

In Otherwise Healthy Adults (No Inflammation)

• Ferritin <15 μg/L: Highly specific for absolute iron deficiency (99% specificity) and indicates completely absent iron stores 1
• Ferritin <30 μg/L: Generally indicates low body iron stores and represents the lower limit of normal for most laboratories 1
• Ferritin <45 μg/L: Provides optimal sensitivity-specificity trade-off (92% specificity) and warrants consideration of investigation and treatment, especially with anemia 1

In Patients with Inflammation or Chronic Disease

The threshold must be raised because ferritin is an acute-phase protein that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency. 1

• Ferritin <100 μg/L with elevated CRP/ESR: Suggests possible iron deficiency in the context of chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure, malignancy) 1
• Ferritin <150 μg/L: Values above this level are unlikely to occur with absolute iron deficiency, even in the presence of inflammation 1

Algorithmic Approach to Diagnosis

Step 1: Measure Ferritin and Assess for Inflammation

• Check ferritin level 1
• Measure inflammatory markers (CRP, ESR) to determine if ferritin may be falsely elevated 1

Step 2: Interpret Ferritin Based on Inflammation Status

If CRP/ESR are normal (no inflammation):

• Ferritin <15 μg/L → Absolute iron deficiency confirmed (99% specific) 1
• Ferritin 15-30 μg/L → Low iron stores, treat as iron deficiency 1
• Ferritin 30-45 μg/L → Borderline; calculate transferrin saturation (TSAT) to confirm 1
• Ferritin >45 μg/L → Iron deficiency less likely, but calculate TSAT to exclude functional iron deficiency 1

If CRP/ESR are elevated (inflammation present):

• Ferritin <100 μg/L → Consider iron deficiency despite inflammation 1
• Ferritin 100-150 μg/L → Calculate TSAT; if <20%, functional iron deficiency likely 1
• Ferritin >150 μg/L → Absolute iron deficiency unlikely even with inflammation 1

Step 3: Calculate Transferrin Saturation (TSAT) for Confirmation

TSAT = (Serum Iron × 100) ÷ Total Iron-Binding Capacity 1

• TSAT <16-20%: Confirms iron deficiency (either absolute or functional) regardless of ferritin level 1
• TSAT ≥20%: Iron deficiency less likely 1

Guideline-Based Recommendations by Population

American Gastroenterological Association (2020)

The AGA strongly recommends using a ferritin cut-off of 45 ng/mL over 15 ng/mL when diagnosing iron deficiency in patients with anemia (strong recommendation, high-quality evidence). 1

British Society of Gastroenterology (2021)

• Ferritin <15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
• Ferritin cut-off of 45 μg/L provides respectable specificity of 0.92 and warrants consideration of GI investigation, especially with chronic inflammatory process and anemia 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Assuming Normal Ferritin Excludes Iron Deficiency

Never interpret ferritin in isolation—always calculate TSAT to assess iron availability for erythropoiesis. 1 Functional iron deficiency can occur with normal or even elevated ferritin if TSAT is <20%, indicating insufficient iron release despite adequate stores 1

Pitfall 2: Missing Iron Deficiency in Inflammatory States

In patients with chronic disease, inflammation, or infection, ferritin levels may appear falsely normal or elevated despite true iron deficiency 1. Always check CRP/ESR and use higher ferritin thresholds (<100 μg/L) in these populations 1

Pitfall 3: Using Laboratory "Normal Ranges" Uncritically

Many laboratory reference ranges (15-150 μg/L for women, 20-200 μg/L for men) are based on population distributions rather than physiologic iron needs 2. Recent evidence suggests that 30-50% of healthy women have no marrow iron stores, and the body's physiologic ferritin threshold may be closer to 50 ng/mL 2, 3

Pitfall 4: Overlooking Non-Anemic Iron Deficiency

Iron deficiency without anemia (ferritin <30-45 μg/L with normal hemoglobin) still causes significant symptoms including fatigue, reduced exercise tolerance, and cognitive impairment, and warrants treatment 1, 4

Nuances in Specific Populations

Premenopausal Women

• GI investigation is conditional rather than mandatory for iron deficiency in premenopausal women, as menstrual blood loss is the most common cause 1
• Reserve bidirectional endoscopy for: age ≥50 years, GI symptoms, positive celiac/H. pylori testing, or failure to respond to adequate oral iron after 8-10 weeks 1

Chronic Kidney Disease Patients

• Absolute iron deficiency defined as ferritin <100 ng/mL combined with TSAT <20% 1
• Functional iron deficiency occurs when ferritin is 100-700 ng/mL but TSAT remains <20% 1

Evidence Quality Considerations

The British Society of Gastroenterology (2021) and American Gastroenterological Association (2020) guidelines represent the highest quality evidence available 1. Both converge on the 45 μg/L threshold as clinically optimal, with the AGA providing a strong recommendation based on high-quality evidence 1. Recent research (2022) supports ferritin ≤50 ng/mL as indicative of early iron deficiency based on hepcidin and soluble transferrin receptor levels 3, though this has not yet been incorporated into major guidelines.