What does a ferritin level of 544 indicate and what are the next steps?

Evaluation and Management of Ferritin Level of 544

A ferritin level of 544 μg/L indicates possible iron overload and requires further evaluation for hemochromatosis or other causes of hyperferritinemia. The next steps should include measuring transferrin saturation, HFE gene testing if transferrin saturation is elevated, and evaluation for other causes of elevated ferritin.

Interpretation of Ferritin Level 544

This ferritin value is significantly elevated compared to normal reference ranges:

• For men: normal range is 20-200 μg/L 1
• For women: normal range is 15-150 μg/L 1

A ferritin level of 544 μg/L falls within the range typically seen in:

• Asymptomatic hemochromatosis (150-1000 μg/L) 1
• Early symptomatic iron overload conditions 1

Diagnostic Algorithm

Step 1: Measure Transferrin Saturation

• Calculate transferrin saturation (serum iron concentration ÷ total iron-binding capacity × 100) 1
• If transferrin saturation ≥45%, proceed with HFE genetic testing 1
• If transferrin saturation <45%, consider other causes of hyperferritinemia 1

Step 2: HFE Genetic Testing (if transferrin saturation ≥45%)

• Test for C282Y and H63D mutations 1
• Possible results:
  • C282Y homozygosity (most common in hereditary hemochromatosis)
  • C282Y/H63D compound heterozygosity
  • Other genotypes

Step 3: Evaluate for Other Causes of Elevated Ferritin

Common non-iron overload causes include:

• Inflammatory conditions (check C-reactive protein) 1
• Malignancy (most common cause of markedly elevated ferritin) 2
• Liver disease (check liver enzymes) 1
• Infection 3
• Alcohol consumption
• Metabolic syndrome

Clinical Considerations

Risk Assessment for Hemochromatosis

• Ferritin <1000 μg/L is a good predictor for absence of cirrhosis in hemochromatosis 1
• Ferritin >1000 μg/L with elevated liver enzymes and platelet count <200 predicts cirrhosis in 80% of C282Y homozygotes 1

Physical Examination Focus

Look specifically for:

• Hepatomegaly
• Skin pigmentation changes
• Joint swelling or arthritis
• Signs of cardiomyopathy
• Endocrine abnormalities (hypothyroidism, hypogonadism) 1

Management Recommendations

1. If hereditary hemochromatosis is confirmed:

   • Initiate therapeutic phlebotomy if ferritin is elevated 1
   • Consider liver biopsy if ferritin >1000 μg/L with abnormal liver enzymes 1

2. If other causes of hyperferritinemia are identified:

   • Treat the underlying condition
   • Monitor ferritin levels during treatment

3. Family screening:

   • Recommend screening for all first-degree relatives if hereditary hemochromatosis is confirmed 1
   • Both genotype (HFE mutation analysis) and phenotype (ferritin and transferrin saturation) should be performed 1

Important Caveats

• Ferritin is an acute phase reactant and can be elevated in inflammatory conditions, infections, and malignancies independent of iron status 1, 2
• A single ferritin measurement may not reflect long-term iron status 1
• Elevated ferritin without elevated transferrin saturation may indicate non-iron overload conditions 1
• Very high ferritin levels (>10,000 μg/L) are more commonly seen in conditions like adult-onset Still's disease, macrophage activation syndrome, or hemophagocytic lymphohistiocytosis 2, 3

Remember that early diagnosis and treatment of hemochromatosis can prevent organ damage and complications such as cirrhosis, diabetes, and cardiomyopathy.