What are the treatment options for abnormal copper and ferritin levels?

Treatment Options for Abnormal Copper and Ferritin Levels

Treatment for abnormal copper and ferritin levels should be tailored to the underlying cause, with specific interventions based on whether levels are elevated or deficient.

Copper Abnormalities

Copper Deficiency

Copper deficiency can lead to significant morbidity and mortality through hematologic and neurologic complications if left untreated.

Diagnosis:

• Consider copper deficiency when serum copper levels are <12 μmol/L with high CRP (>20 mg/L) 1
• Definitive deficiency is indicated by levels <8 μmol/L regardless of CRP 1
• Common presentations include microcytic anemia, neutropenia, and neurological symptoms 2

Treatment:

1. Mild deficiency:

   • Two Forceval tablets daily for 3 months, then recheck levels 1
   • Oral copper supplementation (4-8 mg/day) 2

2. Severe deficiency:

   • Refer for specialist advice 1
   • May require intravenous copper repletion at doses 4-8 times higher than usual nutritional recommendations 2
   • Monitor both copper and zinc levels, as they affect each other's absorption 1

3. Maintenance:

   • Maintain zinc-to-copper ratio of 8-15 mg zinc to 1 mg copper 1
   • Regular monitoring every 3 months during treatment 1

Copper Excess (Wilson's Disease)

Treatment:

1. Initial phase:

   • Penicillamine (250-500 mg/day initially, increased by 250 mg increments every 4-7 days to maximum 1000-1500 mg daily in divided doses) 1, 3
   • Zinc acetate (50 mg three times daily) to block intestinal copper absorption 4

2. Maintenance phase:

   • Continue zinc acetate to maintain negative copper balance 4
   • Dietary modifications to reduce copper intake (avoid chocolate, nuts, shellfish, mushrooms, liver) 3

Ferritin Abnormalities

Iron Deficiency (Low Ferritin)

Diagnosis:

• Definitive iron deficiency: ferritin <15 μg/L (specificity 98%) 5
• Probable iron deficiency in inflammatory states: ferritin <100 μg/L 5

Treatment:

1. Oral iron supplementation as first-line therapy
2. Investigate underlying cause - especially in adult men and postmenopausal women, as 9% of patients >65 years with iron deficiency anemia have gastrointestinal cancer 6

Iron Overload (High Ferritin)

Treatment:

1. Therapeutic phlebotomy:

   • Initial phase: Weekly phlebotomies until serum ferritin <50 μg/L 1, 5
   • Monitor hemoglobin and hematocrit at each phlebotomy session 1
   • If anemia develops, postpone phlebotomy until resolved 1

2. Maintenance phase:

   • Maintain serum ferritin at 50-100 μg/L 1, 5
   • Typically requires phlebotomy every 3-6 months 1
   • Alternative approach: cease phlebotomy with monitoring and restart when ferritin reaches upper limit of normal 1

3. Iron chelation therapy:

   • For transfusion-dependent patients requiring ≥2 units/month for >1 year 1
   • Indicated when serum ferritin >1,000 ng/mL 1
   • Most beneficial for patients with low-risk myelodysplastic syndromes and life expectancy >1 year 1

Special Considerations

Concurrent Abnormalities

When both copper and iron levels are abnormal:

1. Low copper with high ferritin:

   • Rule out aceruloplasminemia (ACP) - characterized by absent/low ceruloplasmin, low serum copper, high ferritin, and iron accumulation in liver, pancreas, and brain 1
   • Consider iron chelation therapy for ACP 1

2. Low copper and low ferritin:

   • Investigate for malabsorption syndromes 1
   • Consider history of bariatric surgery, which is a common cause of copper deficiency 2

3. Post-bariatric surgery patients:

   • Higher risk for both copper and iron deficiencies 1, 2
   • May require more aggressive supplementation and monitoring

Monitoring

• For copper: Check levels every 3 months during treatment 1
• For ferritin: Monitor every 3 months in patients receiving transfusions 1
• Always check both copper and zinc levels when supplementing either mineral 1

Pitfalls to Avoid

1. Don't overlook neurological symptoms in copper deficiency, which may only be partially reversible even with treatment 7
2. Don't supplement iron without investigating the cause of deficiency in adult men and postmenopausal women
3. Avoid vitamin C supplements during iron overload treatment as they enhance iron absorption and may increase free-radical activity 5
4. Don't supplement zinc without monitoring copper as high zinc intake can induce copper deficiency 1
5. Don't assume ferritin accurately reflects iron stores during inflammation - values up to 100 μg/L may still indicate iron deficiency in inflammatory states 5