What is the significance of a ferritin level of 210 ng/mL in an adult and how should it be evaluated and managed?

Ferritin 210 ng/mL: Clinical Significance and Management

Initial Interpretation

A ferritin level of 210 ng/mL falls within the normal reference range for most adults and does not indicate iron overload or deficiency in isolation. This value requires interpretation alongside transferrin saturation and clinical context to determine its significance. 1

Normal Reference Values

• Men: Average serum ferritin is 135 μg/L, with an upper limit of normal around 250 μg/L 1
• Women: Average serum ferritin is 43 μg/L, with an upper limit of normal around 200 μg/L 1
• Your value of 210 ng/mL sits just above the female upper limit but well below concerning thresholds for iron overload 1

Critical Next Step: Measure Transferrin Saturation

You must obtain a fasting transferrin saturation (TS) to properly interpret this ferritin level. Ferritin alone cannot distinguish between true iron overload and secondary causes of elevation. 2, 3

Interpretation Algorithm Based on TS:

If TS ≥ 45%:

• Suspect primary iron overload (hereditary hemochromatosis) 2, 3
• Order HFE genetic testing for C282Y and H63D mutations immediately 2, 3
• C282Y homozygosity or C282Y/H63D compound heterozygosity confirms HFE-related hemochromatosis 2, 3

If TS < 45%:

• Iron overload is excluded with >90% certainty 3
• The ferritin elevation reflects secondary causes: inflammation, liver disease, metabolic syndrome, or alcohol use 2, 3
• Do NOT proceed with HFE genetic testing 3

Secondary Causes to Evaluate (When TS < 45%)

Over 90% of elevated ferritin cases are NOT due to iron overload. 3 The most common culprits include:

Liver Disease

• Chronic alcohol consumption increases iron absorption and causes hepatocellular injury 3
• Non-alcoholic fatty liver disease (NAFLD)/metabolic syndrome causes ferritin elevation reflecting hepatocellular injury and insulin resistance rather than true iron overload 2, 3
• Viral hepatitis B or C elevates ferritin through hepatic inflammation 3
• Check ALT, AST, and consider abdominal ultrasound 3

Inflammatory Conditions

• Ferritin is an acute-phase reactant that rises during inflammation, infection, and tissue damage independent of iron stores 2, 1, 3
• Check CRP and ESR to detect occult inflammation 3
• Chronic inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease) elevate ferritin as an acute-phase response 3

Metabolic Syndrome

• Obesity, glucose intolerance, and dyslipidemia commonly elevate ferritin 3
• Nearly 40% of adults with abnormal liver tests have fatty liver on ultrasound 3

Malignancy

• Solid tumors and lymphomas can elevate ferritin 3
• Check CBC with differential to assess for hematologic malignancy 3

Cell Necrosis

• Muscle injury, hepatocellular necrosis, or tissue breakdown releases ferritin from lysed cells 3
• Check creatine kinase (CK) if muscle injury suspected 3

Risk Stratification by Ferritin Level

Ferritin < 1,000 μg/L (your level is 210):

• Low risk of organ damage 2, 3
• Negative predictive value of 94% for advanced hepatic fibrosis 3
• No liver biopsy needed at this level unless other concerning features present 3

Ferritin 1,000–10,000 μg/L:

• Higher risk of advanced fibrosis/cirrhosis if iron overload present 3
• In C282Y homozygotes, ferritin >1,000 μg/L with elevated aminotransferases and platelet count <200,000/μL predicts cirrhosis in ~80% 2, 3

Ferritin > 10,000 μg/L:

• Rarely represents simple iron overload 3
• Requires urgent specialist referral for life-threatening conditions (hemophagocytic lymphohistiocytosis, adult-onset Still's disease) 2, 3

Specific Clinical Contexts

Hemochromatosis Screening Thresholds

• In the HEIRS study, elevated ferritin was defined as >300 μg/L in men and >200 μg/L in women 2
• Your level of 210 ng/mL is at the threshold for women but requires TS ≥45% before suspecting hemochromatosis 2
• A serum ferritin >250 μg/L in men and >200 μg/L in women was positive in 77% and 56% of C282Y homozygotes, respectively 2

Chronic Kidney Disease

• In CKD patients receiving erythropoiesis-stimulating agents, target ferritin >200 ng/mL to optimize anemia correction and minimize ESA requirements 2
• Ferritin 100-700 ng/mL with TS <20% may represent functional iron deficiency that responds to IV iron 2, 3

Inflammatory Bowel Disease

• Ferritin <30 μg/L indicates absolute iron deficiency 3
• Ferritin 30-100 μg/L with TS <16% suggests combined iron deficiency and anemia of chronic disease 3
• Ferritin >100 μg/L with TS <16% indicates predominant anemia of chronic disease 3

Critical Pitfalls to Avoid

Never diagnose iron overload based on ferritin alone without confirming TS ≥45%. 2, 3 Ferritin rises as an acute-phase reactant in inflammation, liver disease, malignancy, and tissue necrosis independent of iron stores. 2, 1, 3

Do not order HFE genetic testing when TS <45%. 3 This leads to misdiagnosis and unnecessary phlebotomy. 3

Do not assume normal ferritin excludes iron deficiency in inflammatory states. 1 In patients with inflammation, ferritin values up to 100 μg/L may still be compatible with true iron deficiency. 1

Recognize that a single TS measurement may be normal in up to 33% of C282Y homozygotes due to biological variability. 3 Repeat testing may be needed if clinical suspicion remains high. 3

Recommended Workup

1. Order fasting transferrin saturation immediately 2, 3
2. Check inflammatory markers: CRP, ESR 3
3. Assess liver function: ALT, AST, complete metabolic panel 3
4. Complete blood count with differential to assess for anemia or hematologic malignancy 3
5. Consider abdominal ultrasound if liver disease suspected 3

When to Refer to Specialist

• Ferritin >1,000 μg/L with elevated bilirubin 3
• Ferritin >10,000 μg/L regardless of other findings 3
• Confirmed TS ≥45% on repeat testing 3
• Clinical evidence of cirrhosis (platelet count <200,000/μL, elevated bilirubin, hepatomegaly) 3
• Confirmed C282Y homozygosity requiring therapeutic phlebotomy 3

Bottom Line

At 210 ng/mL, your ferritin level is borderline elevated and requires transferrin saturation measurement to determine significance. If TS <45%, this represents secondary hyperferritinemia from inflammation, liver disease, or metabolic causes—not iron overload. Treat the underlying condition, not the ferritin number itself. 3