What are the symptoms and treatment options for elevated ferritin levels?

Symptoms and Treatment Options for Elevated Ferritin Levels

Symptoms of Elevated Ferritin

Elevated ferritin levels often present with no specific symptoms until iron overload causes organ damage, with symptoms varying based on the underlying cause and severity of elevation. 1

The clinical presentation depends on the degree of elevation and underlying cause:

Mild to Moderate Elevation (100-800 ng/mL)

• Often asymptomatic
• May be associated with:
  • Fatigue
  • Malaise
  • Joint pain (particularly metacarpophalangeal joints) 2
  • Mild elevation of liver enzymes 2

Substantial Elevation (>800 ng/mL)

• Arthropathy of metacarpophalangeal joints (3.6-fold increased risk) 2
• Arthropathy of upper ankle joints 2
• Elevated liver enzymes, especially ALT (10.1-fold increased risk) 2
• Abdominal pain
• Unexplained weight loss
• Skin hyperpigmentation (bronze diabetes)
• Cardiac symptoms (arrhythmias, heart failure)
• Diabetes or glucose intolerance
• Hypogonadism and other endocrine disorders

Severe Elevation (>1000 ng/mL)

• High risk of cirrhosis (20-45%) if true iron overload exists 1
• Organ damage manifestations:
  • Liver: hepatomegaly, elevated liver enzymes, cirrhosis
  • Heart: cardiomyopathy, arrhythmias, heart failure
  • Pancreas: diabetes mellitus
  • Joints: arthritis, particularly of metacarpophalangeal joints
  • Skin: hyperpigmentation
  • Endocrine glands: hypothyroidism, hypogonadism

Diagnostic Approach

1. Complete iron studies including:

   • Serum ferritin
   • Transferrin saturation (TSAT)
   • Serum iron
   • Total iron binding capacity (TIBC) 1

2. Interpretation of ferritin levels:

   • <10 μg/L: Severe iron deficiency
   • <30 μg/L: Iron deficiency without inflammation
   • 30-100 μg/L: Possible iron deficiency or anemia of chronic disease
   • 50-100 μg/L: Target maintenance range for most patients

   • 100 μg/L: Possible anemia of chronic disease or iron overload

   • 1000 μg/L: High risk of cirrhosis if true iron overload exists 1

3. Additional testing for patients with elevated ferritin:

   • Liver function tests
   • Complete blood count
   • Renal function tests
   • Genetic testing for HFE gene mutations if TSAT >45% 1
   • Consider liver MRI for iron quantification 3

Treatment Options

Treatment depends on the underlying cause and severity of iron overload:

1. For True Iron Overload

Therapeutic phlebotomy is the first-line treatment for patients with confirmed iron overload, with a goal to reduce ferritin levels to 50-100 μg/L. 1

• Phlebotomy Protocol:

  • 400-500 mL blood weekly or biweekly
  • Continue until ferritin levels reach 50-100 μg/L
  • Monitor complete blood count, liver function, and renal function monthly 1

• Iron Chelation Therapy for patients who cannot undergo phlebotomy:

  • Indicated for patients with ferritin levels >1,000 ng/mL and transfusion-dependent conditions 1, 4
  • Options include:
    • Deferasirox: Initial dose 14 mg/kg/day orally for patients with eGFR >60 mL/min/1.73m² 4
    • Dose adjustments based on monthly serum ferritin monitoring
    • Maximum dose: 28 mg/kg/day (not recommended to exceed) 4
  • Monitor for adverse effects:
    • Renal function
    • Liver function
    • Auditory and ocular abnormalities
    • Cytopenias 4

2. For Secondary Causes of Hyperferritinemia (90% of cases) 5

• Metabolic Syndrome/NAFLD:

  • Weight loss
  • Regular physical activity
  • Reduced red meat consumption
  • Limited alcohol intake
  • Avoidance of iron supplements 1

• Inflammatory Conditions:

  • Treat the underlying condition
  • Monitor ferritin levels to assess response

• Malignancy:

  • Refer to appropriate specialist for management of underlying malignancy 6

• Alcohol-Related Liver Disease:

  • Alcohol cessation
  • Liver-supportive care

Monitoring

• Monitor serum ferritin monthly during active treatment 1, 4
• For patients on deferasirox:
  • If ferritin falls below 1000 mcg/L at 2 consecutive visits, consider dose reduction
  • If ferritin falls below 500 mcg/L, interrupt therapy 4
• Annual monitoring of iron studies if no iron overload is detected
• More frequent monitoring (every 3 months) during treatment if true iron overload is confirmed 1

When to Refer to a Specialist

• Ferritin levels >1000 μg/L
• Unclear cause of elevated ferritin after initial evaluation
• Evidence of organ damage
• For consideration of liver biopsy if liver enzymes are elevated 1
• For cardiac evaluation with ECG and echocardiography in severe iron overload 1

Common Pitfalls to Avoid

• Assuming all elevated ferritin indicates iron overload (90% of cases are due to non-iron overload conditions) 5
• Initiating phlebotomy without confirming true iron overload
• Failing to investigate underlying causes of secondary hyperferritinemia
• Overlooking organ damage in patients with chronic iron overload
• Continuing iron supplementation in patients with elevated ferritin