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

Treatment of Hypercupremia (Elevated Copper Levels)

The treatment for elevated copper levels primarily depends on the underlying cause, with Wilson's disease being the most common pathological cause requiring chelation therapy with D-penicillamine, trientine, or zinc acetate. 1

Diagnostic Considerations Before Treatment

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

1. Wilson's Disease Assessment:

   • Measure serum ceruloplasmin (extremely low levels <50 mg/L strongly suggest Wilson's disease)
   • Check 24-hour urinary copper excretion (typically >100 μg/24h in symptomatic Wilson's disease)
   • Look for Kayser-Fleischer rings in the cornea
   • Consider liver biopsy for hepatic copper concentration (>250 μg/g dry weight confirms Wilson's disease)
   • Evaluate for neurological and hepatic manifestations

2. Other Causes:

   • Acute liver failure of any etiology
   • Chronic cholestasis
   • Copper intoxication from ingestion or poisoning
   • Monoclonal immunoglobulinopathies 2

Treatment Algorithm for Hypercupremia

1. Wilson's Disease Treatment

A. Initial Treatment for Symptomatic Patients:

• Chelation therapy is first-line treatment for symptomatic patients 1, 3:

  • D-penicillamine: Starting at 250-500 mg/day, increasing to 1-1.5 g/day in 2-4 divided doses
  • Trientine: Alternative for patients intolerant to D-penicillamine

• Important caution: Neurological symptoms may worsen initially during chelation therapy. Despite this, treatment should not be withdrawn as temporary interruption increases the risk of sensitivity reactions upon resumption 4

B. Maintenance Treatment:

• Zinc acetate: 50 mg three times daily (elemental zinc)
  • Must be taken on an empty stomach (at least 1 hour before or 2-3 hours after meals)
  • Works by blocking intestinal absorption of copper and inducing metallothionein
  • Not recommended for initial therapy of symptomatic patients due to delayed action 3

C. Dietary Copper Restriction:

• Limit dietary copper intake to 1-2 mg/day
• Avoid copper-rich foods: chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and copper-enriched cereals 4
• Use distilled or demineralized water if drinking water contains >0.1 mg/L copper

2. Acute Severe Hypercupremia

For fulminant hepatic failure with severe hypercupremia:

• Therapeutic plasma exchange (TPE) may be used as a bridge to liver transplantation 5
• Liver transplantation is indicated for patients with fulminant hepatic failure

3. Copper Toxicity from External Sources

• Remove source of exposure
• Chelation therapy as above
• Supportive care for end-organ damage

Monitoring Treatment Efficacy

1. Clinical monitoring:

   • Neuropsychiatric evaluations including speech
   • Liver function tests
   • Physical examination for Kayser-Fleischer rings

2. Laboratory monitoring:

   • 24-hour urinary copper excretion (target <125 μg/24h on zinc therapy) 3
   • Non-ceruloplasmin plasma copper (target <20 μg/dL)
   • Complete blood count (to monitor for anemia)
   • Liver function tests

3. Frequency of monitoring:

   • At least twice yearly for stable patients
   • More frequently during initial phase of treatment
   • More frequently if symptoms worsen or side effects develop 1

Pitfalls and Caveats

1. Zinc and copper interaction: When giving additional zinc and copper supplements, maintain a ratio of 8-15 mg zinc to 1 mg copper, as each affects the absorption of the other 1

2. Copper deficiency risk: Prolonged treatment with chelating agents can lead to copper deficiency. Monitor for signs of deficiency including anemia, leukopenia, and neurological symptoms 6, 7

3. Medication compliance: Strict adherence to the treatment regimen is essential for optimal control of copper distribution and metabolism 3

4. Pregnancy considerations: Women with Wilson's disease should avoid pregnancy for 12-18 months after starting treatment to allow weight stabilization and establishment of a varied nutritious diet 1

5. Sample collection: Urine and plasma for copper determinations should be collected in copper-free containers and assayed with equipment capable of accurately measuring copper at levels as low as 0.01 μg/mL 3

By following this structured approach to the treatment of hypercupremia, clinicians can effectively manage copper levels while minimizing the risk of complications from both the disease and its treatment.