What should I do for an elevated ferritin level?

Management of Ferritin 448 μg/L

Measure fasting transferrin saturation immediately—this single test determines whether your elevated ferritin represents true iron overload (requiring genetic testing and possible phlebotomy) or a secondary cause (requiring treatment of the underlying condition). 1, 2

Initial Diagnostic Algorithm

Your ferritin of 448 μg/L is elevated but falls well below the 1,000 μg/L threshold associated with significant organ damage risk. 1, 2 The critical next step is measuring transferrin saturation (TS), as ferritin alone cannot distinguish between iron overload and the far more common secondary causes. 1, 2

If Transferrin Saturation ≥45%

• Order HFE genetic testing for C282Y and H63D mutations immediately to diagnose hereditary hemochromatosis. 1, 2, 3
• C282Y homozygotes with elevated TS confirm HFE hemochromatosis and warrant therapeutic phlebotomy. 1, 3
• At your ferritin level (<1,000 μg/L) with normal liver enzymes and age <40 years, you can proceed directly to phlebotomy without liver biopsy. 1, 3
• Screen all first-degree relatives with iron studies and HFE mutation analysis if hemochromatosis is confirmed. 1, 3

If Transferrin Saturation <45%

Iron overload is highly unlikely—over 90% of elevated ferritin cases with normal TS are caused by inflammation, liver disease, metabolic syndrome, or alcohol use, not iron accumulation. 1, 2

Evaluate for these common secondary causes:

• Liver disease: Check ALT, AST, and consider abdominal ultrasound to assess for NAFLD (present in ~40% of patients with abnormal liver tests), alcoholic liver disease, or viral hepatitis. 1, 2, 3
• Inflammatory conditions: Measure CRP and ESR to detect occult inflammation from chronic diseases, infections, or rheumatologic conditions. 1, 2, 3
• Metabolic syndrome: Assess for obesity, insulin resistance, dyslipidemia—ferritin elevation in NAFLD reflects hepatocellular injury and metabolic stress, not iron overload. 1, 2, 3
• Alcohol consumption: Obtain detailed history, as chronic alcohol use increases iron absorption and causes hepatocellular injury. 1, 2
• Malignancy: Consider age-appropriate cancer screening if unexplained weight loss, lymphadenopathy, or B symptoms are present. 1, 2

Risk Stratification

Your ferritin of 448 μg/L carries low risk of organ damage:

• Ferritin <1,000 μg/L has a 94% negative predictive value for advanced liver fibrosis in hemochromatosis patients. 1, 2, 3
• No patient with ferritin <1,000 μg/L had cirrhosis in validation studies, but all patients with cirrhosis had ferritin >1,000 μg/L. 1
• The critical threshold for considering liver biopsy is ferritin >1,000 μg/L combined with elevated liver enzymes or platelet count <200,000/μL. 1, 2, 3

Management Based on Underlying Cause

For Confirmed Hemochromatosis (TS ≥45% + C282Y homozygote)

• Initiate weekly phlebotomy removing 500 mL blood until ferritin reaches 50-100 μg/L. 1, 3
• Check hemoglobin/hematocrit before each procedure; allow no more than 20% decline from baseline. 1, 3
• Monitor ferritin every 10-12 phlebotomies during induction phase. 1, 3
• Once target ferritin is achieved, continue maintenance phlebotomy every 2-4 months to keep ferritin 50-100 μg/L. 1, 3
• Avoid vitamin C supplements and all iron supplements—vitamin C accelerates iron mobilization and increases oxidative stress. 3

For Secondary Hyperferritinemia (TS <45%)

Treat the underlying condition, not the elevated ferritin itself. 1, 3

• NAFLD/metabolic syndrome: Weight loss, exercise, and metabolic syndrome management are the primary interventions. 1, 2, 3
• Inflammatory conditions: Disease-specific anti-inflammatory therapy. 1
• Alcohol-related: Abstinence from alcohol. 1, 2
• Do NOT perform phlebotomy for secondary hyperferritinemia—it will not address the root cause and is not indicated. 1, 3

Critical Pitfalls to Avoid

• Never use ferritin alone to diagnose iron overload—ferritin is an acute-phase reactant elevated in inflammation, liver disease, and tissue necrosis independent of iron stores. 1, 2, 3
• Do not assume iron overload when TS <45%—in the general population, iron overload is NOT the most common cause of elevated ferritin. 1, 2
• Do not supplement iron when ferritin is elevated unless you have documented iron deficiency with low TS (<20%) and ferritin paradoxically elevated due to inflammation. 1, 2
• Do not delay measuring transferrin saturation—this is the single most important discriminator between true iron overload and secondary causes. 1, 2, 3

When to Refer to Specialist

• Ferritin rises above 1,000 μg/L despite treatment of underlying condition. 3
• Transferrin saturation ≥45% on repeat testing. 3
• Evidence of advanced liver disease (elevated bilirubin, low platelets, abnormal synthetic function). 3
• Ferritin >10,000 μg/L (suggests life-threatening conditions like adult-onset Still's disease or hemophagocytic lymphohistiocytosis requiring urgent evaluation). 1, 2, 3

Monitoring Plan

• Recheck ferritin and transferrin saturation in 3 months after addressing any identified secondary causes. 1, 3
• If TS was initially <45% and ferritin normalizes with treatment of underlying condition, no further iron-specific workup is needed. 1, 2
• If ferritin remains elevated or rises, repeat full evaluation including liver function tests and inflammatory markers. 1, 3