What is the treatment for hypercupremia (elevated copper levels)?

Treatment of Hypercupremia (Elevated Copper Levels)

The first-line treatment for hypercupremia is chelation therapy with D-penicillamine or trientine, followed by maintenance therapy with zinc acetate for long-term management. 1

Diagnosis and Evaluation

Before initiating treatment, it's essential to determine the cause of hypercupremia:

• Wilson's disease: The most common cause requiring treatment

  • Diagnostic criteria include:
    • Low ceruloplasmin (<50 mg/L or <5 mg/dL)
    • Elevated non-ceruloplasmin bound copper (>25 µg/dL)
    • 24-hour urinary copper excretion >100 µg/24 hours (>1.6 µmol/24 hours) 2
    • Hepatic copper content >4 µmol/g dry weight 2

• Other causes of hypercupremia that may not require specific copper-lowering treatment:

  • Inflammatory conditions (due to increased ceruloplasmin)
  • Infections, hemopathies, hemochromatosis
  • Hyperthyroidism, liver cirrhosis, hepatitis
  • Pregnancy
  • Oral contraceptive use 3

Treatment Algorithm

1. Initial Treatment for Symptomatic Patients

• Chelation therapy is the first-line treatment for symptomatic patients 1

  • D-penicillamine: Start with 250-500 mg/day, increase by 250 mg increments every 4-7 days to a maximum of 1000-1500 mg/day in 2-4 divided doses 2

    • Take on an empty stomach, at least 1 hour before or 2 hours after meals
    • Monitor for side effects (fever, cutaneous eruptions, lymphadenopathy, neutropenia, thrombocytopenia, proteinuria) 2

  • Trientine: Alternative chelator (750-1500 mg/day in 2-3 divided doses) if D-penicillamine is not tolerated 1

• Caution: Neurological symptoms may worsen initially during chelation therapy but typically improve within 1-3 months 4

2. Maintenance Treatment

• Zinc acetate: 50 mg three times daily 1, 5

  • Mechanism: Induces intestinal metallothionein production, which binds copper and prevents absorption
  • Take on an empty stomach, at least 1 hour before or 2-3 hours after meals 5
  • Capsules should be swallowed whole, not opened or chewed 5

• Dietary modifications:

  • Avoid foods with high copper content: shellfish, nuts, chocolate, mushrooms, organ meats 2, 1
  • Use distilled or demineralized water if drinking water contains >0.1 mg/L of copper 4

3. Special Situations

• Fulminant hepatic failure due to Wilson's disease:

  • Consider therapeutic plasma exchange as a bridge to liver transplantation 6
  • Refer for liver transplantation evaluation 2

• Hypercupremia associated with monoclonal immunoglobulins:

  • May require treatment of underlying condition (e.g., multiple myeloma) 7

Monitoring Treatment Efficacy

• Initial monitoring: Every 1-2 months 1

  • Liver function tests
  • Complete blood count
  • Serum copper and ceruloplasmin
  • 24-hour urinary copper excretion
  • Non-ceruloplasmin bound copper calculation

• Maintenance phase monitoring: At least twice yearly 1

• Target parameters:

  • 24-hour urinary copper excretion: 200-500 μg/day (3-8 μmol/day) for patients on chelation therapy 2, 1
  • 24-hour urinary copper excretion: <75 μg/day (1.2 μmol/day) for patients on zinc therapy 1
  • Non-ceruloplasmin bound copper: normalization with effective treatment 2, 1
    • Values <5 μg/dL suggest overtreatment 1

Important Caveats and Pitfalls

1. Never discontinue treatment completely in Wilson's disease as this can lead to intractable hepatic decompensation 2

2. Zinc is not recommended for initial therapy of symptomatic patients due to the delay in its therapeutic effect 5

3. Pregnancy: Treatment must be maintained throughout pregnancy to prevent fulminant hepatic failure 1

4. Drug interactions: Separate zinc administration from other medications by at least 2 hours 5

5. Neurological worsening: May occur during initial treatment with chelators but should not lead to treatment discontinuation unless severe 2, 4

6. Compliance: Strict adherence to the treatment regimen is essential for optimal control of copper metabolism 5