What do ferritin levels indicate in terms of iron stores and what are the implications for diagnosis and treatment of iron deficiency anemia or iron overload?

What Ferritin Levels Mean

Ferritin is the most specific and earliest indicator of total body iron stores, with each 1 μg/L of serum ferritin corresponding to approximately 10 mg of stored iron. 1

Normal Reference Values

• Adult men: Average serum ferritin is 135 μg/L 1
• Adult women: Average serum ferritin is 43 μg/L 1
• Children (6-24 months): Average serum ferritin is approximately 30 μg/L 1

Interpreting Low Ferritin: Iron Deficiency

Diagnostic Thresholds Without Inflammation

Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and definitively confirms the diagnosis. 1, 2

• Ferritin 15-30 μg/L indicates depleted iron stores and generally warrants treatment 1
• Ferritin <30 μg/L is diagnostic of iron deficiency in adults without inflammatory conditions 3
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (92% specificity) and may justify gastrointestinal investigation 1, 2

Critical Caveat: Ferritin as an Acute-Phase Reactant

Ferritin rises during inflammation, infection, or tissue damage independent of iron status, potentially masking true iron deficiency. 4, 1

• When inflammation is present (elevated CRP or ESR), the diagnostic threshold shifts upward to ferritin <100 μg/L to indicate iron deficiency 4, 1, 2
• In inflammatory conditions, ferritin 30-100 μg/L with transferrin saturation <16% suggests mixed iron deficiency (both absolute deficiency and anemia of chronic disease) 4
• Ferritin >100 μg/L with transferrin saturation <16% in the presence of inflammation indicates anemia of chronic disease (inflammatory iron block) rather than true iron deficiency 4

Complementary Testing Required

Ferritin alone provides incomplete information—always interpret alongside transferrin saturation (TSAT) and inflammatory markers. 4, 1

• TSAT <16-20% is a sensitive marker for iron deficiency, though specificity is only 40-50% 4, 1
• Calculate TSAT using: (serum iron × 100) ÷ total iron-binding capacity 1
• Measure CRP and ESR to determine if ferritin elevation reflects inflammation rather than adequate iron stores 4
• Soluble transferrin receptor (sTfR) remains elevated in true iron deficiency but normal in anemia of chronic disease, making it valuable when ferritin and TSAT are discordant 4

Interpreting High Ferritin: Iron Overload

Ferritin >150 μg/L rarely occurs with absolute iron deficiency, even in the presence of inflammation. 1

• Elevated ferritin in the absence of inflammation or liver disease indicates increased iron stores and requires investigation for the site of iron overload 5
• In chronic kidney disease patients on dialysis, ferritin 500-1200 ng/mL with TSAT <25% may still warrant IV iron to improve hemoglobin 1
• Iron overload concerns primarily arise when ferritin chronically exceeds 1000 ng/mL 1
• Genetic disorders such as hereditary hemochromatosis (HFE-related), hereditary hyperferritinemia-cataract syndrome, and ferroportin disease can present with unexplained hyperferritinemia 5

Clinical Stages of Iron Deficiency

Iron deficiency progresses through stages, with ferritin declining first before anemia develops. 3

• Stage 1 (Iron depletion): Low ferritin (<30 μg/L) with normal hemoglobin—this is "iron deficiency without anemia" 1, 3
• Stage 2 (Iron-deficient erythropoiesis): Low ferritin, low TSAT, elevated sTfR, but hemoglobin still normal 4
• Stage 3 (Iron deficiency anemia): Low ferritin, low TSAT, low hemoglobin, microcytic/hypochromic red cells 4, 3

Symptoms Even Without Anemia

Depleted iron stores cause significant symptoms including fatigue, exercise intolerance, restless legs syndrome (32-40%), and pica (40-50%), even when hemoglobin remains normal. 1, 3

Diagnostic Algorithm for Low Ferritin

1. If ferritin <15 μg/L: Absolute iron deficiency confirmed—initiate oral iron supplementation immediately and investigate source of iron loss 1

2. If ferritin 15-30 μg/L: Iron deficiency with low stores likely—recommend iron-rich diet and consider oral iron supplementation 1

3. If ferritin 30-100 μg/L: Check CRP/ESR 4

   • If CRP/ESR elevated: Mixed picture of true iron deficiency and anemia of chronic disease—address underlying inflammatory condition and check TSAT 4
   • If CRP/ESR normal: Absolute iron deficiency—initiate iron supplementation 4

4. If ferritin >100 μg/L with low TSAT: Check CRP/ESR 4

   • If CRP/ESR elevated: Anemia of chronic disease (inflammatory iron block)—treat underlying inflammatory condition as primary intervention 4
   • If CRP/ESR normal: Consider functional iron deficiency or check sTfR to confirm 4

Treatment Implications

Oral iron supplementation (ferrous sulfate 30-60 mg elemental iron daily or alternate-day dosing) is first-line therapy for most patients with confirmed iron deficiency. 1, 3

• Alternate-day dosing (60 mg every other day) may improve absorption and reduce gastrointestinal side effects compared to daily dosing 1
• Repeat CBC and ferritin in 8-10 weeks to assess response; target ferritin >100 ng/mL to restore iron stores 1
• Intravenous iron is indicated for oral iron intolerance, malabsorption (celiac disease, post-bariatric surgery), chronic inflammatory conditions (CKD, heart failure, IBD, cancer), ongoing blood loss, and during second/third trimesters of pregnancy 3

Monitoring Recommendations

• For patients with recurrent low ferritin (menstruating females, vegetarians, athletes), screen ferritin every 6-12 months 1
• In ulcerative colitis patients in remission, monitor every 12 months; those with mild disease should be monitored every 6 months 4