What are the implications of hypercupremia (elevated copper levels)?

From the Guidelines

Elevated copper levels in the body, known as hypercupremia, typically require medical intervention with chelation therapy, such as zinc acetate (150 mg elemental zinc/day) or trientine (750-1500 mg/day), to bind to copper and help eliminate it from the body, as recommended by the most recent guidelines 1.

Treatment Overview

The specific treatment depends on the underlying cause, with Wilson's disease being the most common genetic cause requiring lifelong therapy.

• For acute copper toxicity, immediate medical attention is necessary, possibly including gastric lavage if ingestion was recent.
• Dietary modifications are also important, avoiding copper-rich foods like liver, shellfish, chocolate, nuts, and mushrooms.
• Regular monitoring of copper levels through blood and urine tests is essential to adjust treatment.

Monitoring and Adjustments

• Urinary copper excretion should be measured to assess treatment efficacy, aiming for levels less than 1.6 µmol per 24 h on stable treatment with zinc 1.
• Non-ceruloplasmin-bound copper should also be monitored to ensure effective treatment.

Potential Side Effects and Considerations

• Zinc has few side effects, but gastric irritation and immunosuppressant effects are possible 1.
• Trientine may cause sideroblastic anemia, lupus-like reactions, and other adverse effects, although these are rare 1.
• Penicillamine is associated with numerous side effects, including nephrotoxicity, neurological worsening, and hematological toxicity, and is generally considered less safe than zinc or trientine 1.

From the FDA Drug Label

Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal-recessive defect that leads to an accumulation of copper far in excess of metabolic requirements The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread Copper is also deposited as characteristic, asymptomatic, golden-brown Kayser-Fleischer rings in the corneas of all patients with cerebral symptomatology and some patients who are either asymptomatic or manifest only hepatic symptomatology

The treatment for elevated copper levels is to minimize dietary intake of copper and to promote excretion and complex formation (i.e., detoxification) of excess tissue copper.

• Dietary restrictions include a daily diet that contains no more than 1 or 2 mg of copper, excluding foods with high copper content such as chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and cereals enriched with copper.
• Copper chelating agents such as penicillamine capsules or zinc acetate can be used to promote excretion and complex formation of excess tissue copper. Treatment with penicillamine capsules or zinc acetate can produce marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances 2 3.

From the Research

Elevated Copper

Elevated copper levels can be associated with various health issues, including Wilson's disease, a genetic disorder that affects copper metabolism.

• Wilson's disease is characterized by the accumulation of copper in the liver, brain, and other tissues, leading to hepatic, neurologic, and psychiatric disorders 4, 5.
• The diagnosis of Wilson's disease is based on clinical features, biochemical tests, and molecular analysis, including plasma ceruloplasmin concentration, 24-hour urinary copper excretion, and copper content in the liver 5.
• Treatment options for Wilson's disease include chelating agents, such as penicillamine and trientine, and zinc salts, which can help reduce copper levels and prevent further damage 4, 5, 6.
• In some cases, patients with Wilson's disease may experience side effects from chelating agents, such as penicillamine-related lichenoid dermatitis, and may require alternative treatments, such as zinc acetate 4, 7.
• Accurate measurement of hepatic copper content via liver biopsy is important for the adequate management of Wilson's disease 7.
• Copper deficiency, on the other hand, can also have severe consequences, including hematologic and neurologic complications, and may require active intravenous repletion with copper supplements 8.
• Elevated copper levels can be managed with various treatments, including chelating agents and zinc salts, and regular monitoring of copper levels and liver function is crucial to prevent further complications 4, 5, 6, 7.