What are the symptoms and treatment options for iron overload?

Symptoms and Treatment of Iron Overload

Iron overload presents with non-specific symptoms including chronic fatigue, joint pain, and diabetes, and progresses to end-organ failure primarily affecting the pancreas and liver. 1

Clinical Manifestations of Iron Overload

• Early/Common Symptoms:

  • Chronic fatigue 1
  • Joint pain (arthropathy) 1
  • Abdominal pain 1
  • Skin pigmentation changes 1

• Endocrine Manifestations:

  • Diabetes mellitus 1
  • Hypogonadism 1

• Cardiac Manifestations:

  • Cardiomyopathy 1
  • Cardiac dysrhythmias (can lead to sudden death) 1
  • Heart failure (may be refractory to treatment in advanced cases) 1

• Hepatic Manifestations:

  • Elevated liver enzymes 1
  • Progressive fibrosis 1
  • Cirrhosis 1
  • Hepatocellular carcinoma (accounts for approximately 30% of hemochromatosis-related deaths) 1

Diagnostic Approach

• Initial Laboratory Testing:

  • Full investigation of iron status should include: 1
    • Plasma iron
    • Transferrin
    • Transferrin saturation
    • Serum ferritin
    • C-reactive protein (CRP)
    • Hepcidin levels
    • Evaluation of red blood cell morphology

• Imaging Studies:

  • MRI with quantitative assessment of iron content (non-invasive method to assess cardiac and hepatic iron load) 1

• Tissue Sampling:

  • Liver biopsy when documentation of hepatic iron concentration and fibrosis staging is necessary 1
  • Qualitative iron determination by Perls' staining followed by quantitative measurement if increased iron stores are detected 1

Treatment Options

For Hereditary Hemochromatosis:

• Phlebotomy (First-line treatment): 1

  • Initial regimen: One phlebotomy (removal of 500 mL of blood) weekly or biweekly
  • Monitor hematocrit prior to each phlebotomy; allow hematocrit to fall by no more than 20% of prior level
  • Check serum ferritin level every 10-12 phlebotomies
  • Stop frequent phlebotomy when serum ferritin falls below 50 ng/mL
  • Continue maintenance phlebotomy at intervals to keep serum ferritin between 25 and 50 ng/mL

• Important Precautions During Treatment: 1

  • Avoid vitamin C supplements during phlebotomy treatment as they can accelerate iron mobilization, potentially saturating transferrin and increasing free-radical activity
  • Monitor for cardiac complications, especially during rapid iron mobilization

For Secondary Iron Overload (due to transfusions or dyserythropoiesis):

• Iron Chelation Therapy: 1, 2
  • Deferoxamine (Desferal): 20-40 mg/kg body weight per day
  • Administration routes: intramuscular, intravenous, or subcutaneous
  • Maximum dose should not exceed 40 mg/kg/day in pediatric patients and 60 mg/kg/day in adults 2
  • Limit vitamin C intake to no more than 200 mg daily 1, 2
  • Consider follow-up liver biopsy to assess adequacy of iron removal 1

Treatment Response and Prognosis

• Responsive Clinical Features: 1

  • Malaise and fatigue
  • Skin pigmentation
  • Insulin requirements in diabetics
  • Abdominal pain
  • Liver enzymes (normalization)
  • Hepatic fibrosis (can reverse in approximately 30% of cases)

• Less Responsive or Non-responsive Features: 1

  • Arthropathy (joint pain)
  • Hypogonadism
  • Established cirrhosis (does not reverse)

• Prognostic Considerations:

  • Early treatment before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 1
  • Hepatocellular carcinoma risk persists in cirrhotic patients even after adequate iron removal, necessitating continued surveillance 1
  • Survival in non-cirrhotic treated patients approaches that of the normal population 1

Important Clinical Pitfalls

• Delayed Diagnosis:

  • Early symptoms are non-specific and may be overlooked 1
  • Organ damage may be irreversible if treatment is initiated after cirrhosis or diabetes develop 1

• Treatment Monitoring:

  • After IV iron infusion, ferritin levels are falsely elevated for 8-10 weeks, so assessment of treatment success should be delayed 1
  • Cardiac complications may increase during rapid mobilization of iron, requiring careful monitoring 1

• Hepatocellular Carcinoma Risk:

  • HCC surveillance is necessary for cirrhotic patients even after successful iron depletion 1