What does a ferritin level of 576 indicate and how is it treated?

Elevated Ferritin of 576 μg/L: Clinical Significance and Management

A ferritin level of 576 μg/L is moderately elevated and requires measurement of transferrin saturation to determine whether this represents true iron overload, inflammation, or liver disease—the next step is to check transferrin saturation and assess for underlying inflammatory or hepatic conditions. 1, 2

Diagnostic Approach

Measure transferrin saturation (TS) immediately alongside repeat ferritin to properly evaluate iron status, as ferritin alone cannot distinguish between iron overload and inflammatory conditions. 1, 2

Interpretation Based on Transferrin Saturation

• If TS ≥ 45%: Suspect hereditary hemochromatosis and proceed to HFE genotype testing (C282Y and H63D mutations). 3, 1, 2

• If TS < 45%: This ferritin level more likely reflects inflammation, liver disease, metabolic syndrome, or alcohol use rather than true iron overload. 1, 2, 4

Common Causes at This Ferritin Level

At 576 μg/L, the most frequent etiologies include:

• Inflammatory conditions: Ferritin acts as an acute-phase reactant and rises with any chronic inflammation, infection, or rheumatologic disease. 1, 2, 5

• Liver disease: Alcoholic liver disease, viral hepatitis (hepatitis C), and non-alcoholic fatty liver disease (NAFLD) commonly elevate ferritin independent of iron stores. 3, 2, 4

• Metabolic syndrome: Obesity, diabetes, and insulin resistance frequently cause hyperferritinemia. 3, 4

• Malignancy: Various cancers can elevate ferritin as part of systemic inflammation. 5, 6

• Chronic kidney disease: Functional iron deficiency in CKD can present with elevated ferritin but low transferrin saturation. 3, 2

Risk Stratification

At ferritin 576 μg/L, the risk of significant organ damage from iron overload is low. 3, 1

• Ferritin < 1000 μg/L carries minimal risk of advanced liver fibrosis or cirrhosis in hemochromatosis patients. 3, 1, 2

• No patient with ferritin < 1000 μg/L had cirrhosis in validation studies of hereditary hemochromatosis. 1

• Organ damage in true hemochromatosis typically requires ferritin levels dramatically higher than 576 μg/L and prolonged iron accumulation. 3

Management Strategy

If Transferrin Saturation ≥ 45%

• Order HFE genetic testing for C282Y and H63D mutations. 1, 2

• If C282Y homozygote confirmed: Initiate therapeutic phlebotomy without liver biopsy (since ferritin < 1000 μg/L and assuming normal liver enzymes and age < 40 years). 3, 1, 2

• Target ferritin of 50-100 μg/L through weekly phlebotomy of 500 mL blood as tolerated. 3, 1

• Screen first-degree relatives with iron studies and HFE mutation analysis. 3, 1

If Transferrin Saturation < 45%

• Evaluate for secondary causes: Check inflammatory markers (CRP, ESR), liver enzymes (ALT, AST), assess alcohol consumption, screen for metabolic syndrome components, and consider viral hepatitis serologies. 1, 2, 4

• Treat the underlying condition rather than the elevated ferritin itself. 1, 2

• Do not initiate phlebotomy for ferritin elevation alone without confirmed iron overload. 3, 1

Special Considerations

Chronic Kidney Disease Context

If the patient has CKD with anemia and ferritin 576 μg/L but transferrin saturation < 25%, intravenous iron may still be beneficial for anemia management despite the elevated ferritin, as this represents functional iron deficiency. 3, 2

The DRIVE study demonstrated that hemodialysis patients with ferritin 500-1200 ng/mL and TS < 25% had significant hemoglobin increases with IV iron therapy. 3

When to Refer to Specialist

Referral to gastroenterology, hematology, or hepatology is appropriate if:

• Ferritin remains > 1000 μg/L on repeat testing. 1, 4

• Transferrin saturation ≥ 45% with confirmed HFE mutations. 1, 2

• Cause of elevated ferritin remains unclear after initial workup. 4

• Evidence of liver disease with elevated transaminases. 1, 2

Critical Pitfalls to Avoid

• Do not use ferritin alone to diagnose iron overload—always measure transferrin saturation concurrently. 1, 2

• Do not initiate phlebotomy based solely on elevated ferritin without confirming iron overload through transferrin saturation and genetic testing. 3, 1

• Do not overlook inflammatory conditions: Ferritin at this level is more commonly due to inflammation or liver disease than true hemochromatosis. 2, 5, 4

• Do not supplement with iron or vitamin C if iron overload is confirmed. 3, 1