When should copper levels be tested in patients with altered mental status?

When to Test Copper Levels in Patients with Altered Mental Status

Copper levels should be tested in patients with altered mental status who have risk factors for copper abnormalities, particularly those with unexplained neurological symptoms, history of bariatric surgery, or signs of liver disease.

Indications for Copper Testing in Altered Mental Status

Primary Indications

• Neurological symptoms accompanying altered mental status:

  • Unexplained sensory and/or motor symptoms 1
  • Gait abnormalities 1
  • Ataxia 2
  • Movement disorders in young patients 1
  • Psychiatric symptoms, especially depression 1

• Risk factors for copper deficiency:

  • History of bariatric surgery 1, 2
  • Malabsorption syndromes 3
  • Prolonged parenteral nutrition 1
  • Unexplained anemia or fatigue 1

• Risk factors for copper excess (Wilson's disease):

  • Unexplained liver disease, especially in young patients 1
  • Family history of Wilson's disease 1
  • Acute hepatitis with hemolytic anemia 1
  • Behavioral changes in adolescents 1

Secondary Indications

• Unexplained pancytopenia 2
• Abnormal liver function tests of unclear etiology 1
• Psychiatric symptoms that appear disproportionate to clinical situation 1
• Patients requiring unusually high insulin doses (for chromium, but copper should be tested concurrently) 1

Diagnostic Approach

For Suspected Wilson's Disease

1. Initial testing:

   • Serum ceruloplasmin (low levels <0.1 g/L strongly suggest Wilson's disease) 1
   • Serum copper (may be low, normal, or high depending on disease stage) 1
   • 24-hour urinary copper excretion (>100 μg/24 hours suggests Wilson's disease) 1

2. Additional testing:

   • Slit-lamp examination for Kayser-Fleischer rings 1
   • Calculation of non-ceruloplasmin bound copper (>25 μg/dL suggests Wilson's disease) 1
   • Consider liver biopsy for hepatic copper content (>4 μmol/g dry weight is diagnostic) 1

For Suspected Copper Deficiency

1. Initial testing:

   • Serum copper levels 1
   • Serum ceruloplasmin 1

2. Additional testing:

   • Complete blood count (look for anemia, neutropenia) 4
   • Nerve conduction studies if neuropathy is suspected 2

Interpretation Challenges

• Ceruloplasmin levels may be falsely normal in Wilson's disease during inflammation 1
• Ceruloplasmin may be low in conditions other than Wilson's disease (malabsorption, aceruloplasminemia, heterozygous carriers) 1, 4
• Serum copper may be elevated in acute liver failure of any etiology, not just Wilson's disease 1
• Non-ceruloplasmin bound copper calculation depends on accurate measurement of both serum copper and ceruloplasmin 1

Clinical Pearls

• Copper deficiency can present with neurological symptoms similar to vitamin B12 deficiency (subacute combined degeneration) 2
• When testing for copper deficiency, always check zinc levels as well, as high zinc supplementation can cause copper deficiency 1
• Maintain a ratio of 8-15 mg zinc to 1 mg copper when supplementing both minerals 1, 5
• Free copper levels (non-ceruloplasmin bound) may correlate with cognitive function even in otherwise normal individuals 6
• Permanent neurological damage can occur if copper deficiency is not diagnosed and treated promptly 2

Remember that copper abnormalities can present with subtle neuropsychiatric symptoms before more obvious physical manifestations appear, making them an important consideration in the workup of altered mental status with unclear etiology.