What is the next step in managing a patient with elevated ferritin (hyperferritinemia) level of 163, normal vitamin B12 and folate levels, and no evidence of iron deficiency?

Management of Elevated Ferritin (163 μg/L) with Normal B12 and Folate

Your ferritin level of 163 μg/L most likely reflects inflammation, metabolic syndrome, or liver disease rather than iron overload, and the critical next step is measuring fasting transferrin saturation to determine if true iron overload exists. 1

Immediate Diagnostic Workup

Order transferrin saturation (TS) immediately - this single test determines your entire diagnostic pathway. 1 Over 90% of elevated ferritin cases are NOT due to iron overload, and TS is the key discriminator. 1, 2

Additional Initial Laboratory Tests

• Complete metabolic panel including AST, ALT to assess for hepatocellular injury 1
• Inflammatory markers: CRP and ESR to detect occult inflammation 1
• Complete blood count with differential to assess for anemia, polycythemia, or hematologic malignancy 1
• Creatine kinase (CK) to evaluate for muscle necrosis 1

Interpretation Algorithm Based on Transferrin Saturation

If TS ≥45%: Suspect Primary Iron Overload

• Order HFE genetic testing for C282Y and H63D mutations to diagnose hereditary hemochromatosis 1
• C282Y homozygotes with elevated iron stores confirm HFE hemochromatosis and can proceed to therapeutic phlebotomy 1
• Consider liver MRI to quantify hepatic iron concentration if genetic testing is positive 3

If TS <45%: Secondary Hyperferritinemia (Most Likely)

At your ferritin level of 163 μg/L with normal TS, focus on these common causes that account for >90% of cases: 1, 2

Evaluate for Metabolic Syndrome/NAFLD

• Assess for: obesity, diabetes, hypertension, dyslipidemia 1
• Ferritin elevation reflects hepatocellular injury and insulin resistance rather than iron overload 1
• Management: weight loss and metabolic syndrome management, not iron removal 1

Assess Alcohol Consumption

• Obtain detailed history of alcohol intake 1
• Chronic alcohol consumption increases iron absorption and causes hepatocellular injury 1

Screen for Inflammatory Conditions

• Check CRP and ESR - elevated markers suggest inflammation as the cause 1
• Ferritin is an acute phase reactant that rises during inflammation independent of iron stores 1
• Common inflammatory causes include infections, chronic rheumatologic diseases, and malignancy 1

Evaluate for Liver Disease

• Review liver enzymes (AST, ALT) for hepatocellular injury 1
• Consider viral hepatitis screening (hepatitis B and C) if risk factors present 1

Risk Stratification by Ferritin Level

Your ferritin of 163 μg/L is well below the critical threshold of 1000 μg/L, which indicates low risk of organ damage. 1

• Ferritin <1000 μg/L has 94% negative predictive value for advanced liver fibrosis in hemochromatosis 1
• Ferritin >1000 μg/L changes management and warrants consideration of liver biopsy if liver enzymes are abnormal 1

Critical Pitfalls to Avoid

• Never use ferritin alone to diagnose iron overload - ferritin is elevated in inflammation, liver disease, malignancy, and tissue necrosis independent of iron stores 1, 2
• Do not assume iron overload when TS <45% - in the general population, iron overload is NOT the most common cause of elevated ferritin 1
• Do not initiate phlebotomy without confirming iron overload through genetic testing and/or liver iron quantification 2

When to Refer to Specialist

Referral to gastroenterologist, hematologist, or physician with iron overload expertise is appropriate if: 2

• Serum ferritin >1000 μg/L 2
• Cause of elevated ferritin remains unclear after initial workup 2
• TS ≥45% with positive HFE genetic testing 1

Most Likely Scenario at Ferritin 163 μg/L

Given your ferritin level is only mildly elevated and B12/folate are normal, the most probable causes are metabolic syndrome/NAFLD, mild inflammation, or modest alcohol consumption. 1, 4 These conditions do not require iron removal therapy but rather treatment of the underlying condition. 1