What is the appropriate management for a patient with hyperferritinemia and increased iron saturation?

Management of Ferritin 163 ng/mL with Iron Saturation 32%

Your patient does not require treatment for iron overload—this ferritin level with a transferrin saturation below 45% indicates a secondary cause of mild hyperferritinemia, not hereditary hemochromatosis or clinically significant iron overload. 1

Why This Patient Does Not Have Iron Overload

• Transferrin saturation is the critical discriminator: A TS of 32% falls well below the 45% threshold required to suspect primary iron overload disorders like hereditary hemochromatosis 1, 2
• Ferritin 163 ng/mL is minimally elevated and falls far below the 1,000 ng/mL threshold associated with organ damage risk 1
• Over 90% of hyperferritinemia cases with normal TS are caused by inflammation, liver disease, metabolic syndrome, alcohol use, or malignancy—not iron overload 2

What You Should Do Next

Identify the underlying cause of mild ferritin elevation:

• Check inflammatory markers: Order CRP and ESR to detect occult inflammation 1
• Assess liver function: Obtain ALT, AST, and complete metabolic panel to evaluate for fatty liver disease, viral hepatitis, or alcohol-related liver injury 1, 2
• Evaluate metabolic syndrome: Screen for obesity, diabetes, hypertension, and dyslipidemia, as NAFLD commonly causes hyperferritinemia with normal TS 2
• Obtain detailed alcohol history: Chronic alcohol consumption disrupts iron metabolism and elevates ferritin independent of true iron overload 2, 3
• Rule out active infection or malignancy: Ferritin rises as an acute phase reactant during infection, and solid tumors or lymphomas can cause persistent elevation 2

What You Should NOT Do

• Do not order HFE genetic testing for C282Y and H63D mutations—this is only indicated when TS ≥45% 1, 2
• Do not initiate therapeutic phlebotomy—this patient has no evidence of iron overload and phlebotomy would be harmful 1
• Do not order liver biopsy or MRI for hepatic iron quantification—these are reserved for confirmed iron overload with ferritin >1,000 ng/mL and elevated TS 1
• Do not restrict dietary iron or avoid iron-containing foods—this is unnecessary at this ferritin level 1

Clinical Context and Pitfalls

Ferritin is a highly sensitive but poorly specific marker that rises with inflammation, liver disease, malignancy, and tissue necrosis independent of actual iron stores 1, 2. The pattern of elevated ferritin with TS <45% essentially rules out hereditary hemochromatosis and indicates a secondary cause 1, 4.

Common pitfall: Ordering HFE genetic testing based on ferritin alone without checking transferrin saturation leads to unnecessary testing and patient anxiety 1. Even when TS is elevated, it has low specificity—approximately 50% of patients with viral hepatitis or alcoholic liver disease have abnormal iron studies that can mimic iron overload 3, 5.

Expected Management Based on Underlying Cause

• If metabolic syndrome/NAFLD: Weight loss, exercise, and management of diabetes/dyslipidemia—treat the underlying condition, not the ferritin 1, 2
• If inflammatory condition: Disease-specific anti-inflammatory therapy 1
• If alcoholic liver disease: Alcohol cessation and supportive care 2, 3
• If viral hepatitis: Antiviral therapy as indicated 2

Monitor ferritin levels based on the underlying condition identified—monthly monitoring is unnecessary unless treating confirmed iron overload 1.