What are the implications and management strategies for a patient with hyperferremia and normal ferritin levels?

Elevated Serum Iron with Normal Ferritin: Implications and Management

Elevated serum iron (228) with normal ferritin levels suggests a non-iron overload condition that requires evaluation for transient causes rather than hereditary hemochromatosis. 1

Differential Diagnosis

When encountering elevated serum iron with normal ferritin, consider:

1. Transient elevation causes:

   • Recent iron supplementation
   • Recent red meat consumption
   • Acute hepatocellular injury
   • Laboratory error

2. Early hemochromatosis:

   • Early-stage hemochromatosis may present with elevated transferrin saturation before ferritin rises 2, 1
   • Transferrin saturation >45% warrants further investigation 1

3. Dysmetabolic iron overload syndrome (DIOS):

   • Associated with metabolic syndrome components
   • Usually presents with elevated ferritin and normal-to-moderately increased transferrin saturation 3

Evaluation Algorithm

1. Confirm the finding:

   • Repeat serum iron measurement, preferably fasting 2
   • Calculate transferrin saturation (serum iron ÷ total iron binding capacity)
   • Verify normal ferritin level

2. If transferrin saturation is elevated (>45%):

   • Consider HFE genotyping for p.C282Y and H63D mutations 1
   • Evaluate for symptoms of hemochromatosis (fatigue, arthralgias, abdominal pain, sexual dysfunction) 2, 1

3. If transferrin saturation is normal:

   • Evaluate for transient causes
   • Consider metabolic workup (lipid panel, glucose, liver enzymes)
   • Assess for non-alcoholic fatty liver disease (NAFLD) 3, 4

4. Consider MRI-based liver iron quantification:

   • Particularly if transferrin saturation >60% or ferritin >963 μg/L 5
   • Can help differentiate true iron overload from other causes of abnormal iron studies

Management Recommendations

1. For transient elevation:

   • Discontinue iron supplements
   • Repeat testing in 2-4 weeks
   • Dietary modification (reduce red meat consumption)

2. For suspected early hemochromatosis:

   • Genetic testing for HFE mutations
   • Family screening if positive
   • Monitor ferritin and transferrin saturation every 3-6 months 1

3. For metabolic hyperferritinemia/DIOS:

   • Lifestyle modifications (weight loss, physical activity)
   • Manage underlying metabolic conditions
   • Phlebotomy is generally not recommended 3

Important Caveats

• Isolated elevated serum iron with normal ferritin is often a transient finding and may not indicate pathology
• Transferrin saturation is more sensitive than serum iron alone for detecting iron overload disorders 1
• Most patients with hereditary hemochromatosis present with both elevated transferrin saturation AND elevated ferritin 2, 1
• Avoid unnecessary phlebotomy therapy in patients without confirmed iron overload 3
• Consider that extremely elevated ferritin (>1000 μg/L) is more commonly associated with malignancy or infection than with rheumatologic diseases 6

Follow-up Recommendations

• Repeat iron studies in 3 months if initial evaluation is inconclusive
• Annual monitoring of iron studies if persistent elevation without clear cause 1
• Consider referral to gastroenterology or hematology if transferrin saturation remains >45% despite normal ferritin 1