What is being tested?

This test measures the amount of copper in the blood, urine, or liver tissue (hepatic). Copper is an essential mineral that the body incorporates into enzymes. These enzymes play a role in the regulation of iron metabolism, formation of connective tissue, energy production at the cellular level, the production of melanin (the pigment that produces skin colour), and the function of the nervous system and brain.

Copper is found in many foods including nuts, chocolate, mushrooms, shellfish, whole grains, dried fruits and liver. Drinking water may acquire copper when it flows through copper pipes and food may acquire it when it is cooked or served in copper dishes. Normally, the body absorbs copper from the intestines, makes it non-toxic by binding it to a protein and transports it to the liver. The liver stores some of the copper and binds most of the rest to a protein called apocaeruloplasmin that when copper is attached, becomes the enzyme caeruloplasmin. About 95 per cent of the copper in the blood is bound to caeruloplasmin with the remainder mostly bound to albumin, transcuprein (another copper-binding protein) and copper-amino acid complexes. The liver excretes excess copper into the bile and it is removed from the body in the stool. Some copper is also excreted in the urine.

Both excesses and deficiencies of copper are rare. Wilson disease, an inherited disorder, can lead to excess storage of copper in the liver, brain and other organs. This can cause tissue damage and signs and symptoms such as:

• anaemia
• nausea, abdominal pain
• jaundice
• fatigue
• behavioural changes
• tremors
• difficulty walking and/or swallowing
• dystonia

Some of these symptoms may also be seen with copper poisoning that is due to acute or chronic environmental exposure to copper or conditions such as liver disease or obstructions that prevent or inhibit copper metabolism and excretion.

Copper deficiencies may occasionally occur in patients who have conditions associated with severe malabsorption, such as cystic fibrosis and coeliac disease and in infants exclusively fed cow-milk formulas. Manifestations may include neutropenia, osteoporosis and microcytic anaemia. A rare X-linked genetic condition called Menke's disease leads to copper deficiency in the brain and liver of affected infants. The disease, which affects primarily males, is associated with seizures, delayed development, abnormal artery development in the brain and unusual grey brittle kinky hair.

How is it used?

Copper testing is primarily ordered to help diagnose Wilson disease, a rate inherited disorder that can lead to excess storage of copper in the liver, brain and other organs. The tests most typically ordered are a total and/or free (unbound) blood copper test along with a caeruloplasmin level. If these tests are abnormal or equivocal they may be followed by a 24-hour urine copper test to measure copper excretion and a hepatic (liver) copper test to evaluate copper storage. Genetic testing may also be performed to detect mutations in the ATP7B gene if Wilson's disease is suspected.

Less commonly, if copper toxicity, copper deficiency or a disorder that is inhibiting copper metabolism is suspected, blood and/or urine copper tests along with caeruloplasmin can be used to evaluate the someone's condition. One or more copper tests may be ordered to help monitor the effectiveness of treatment for Wilson's disease, copper excess or copper deficiency.

When is it requested?

One or more copper tests are ordered along with caeruloplasmin when someone has signs and symptoms that may be due to Wilson disease, excess copper storage, copper poisoning or due to a copper deficiency.
Signs and symptoms of Wilson disease, excess copper or copper poisoning  may include:

• anaemia
• nausea, abdominal pain
• jaundice
• fatigue
• behavioural changes
• tremors
• difficulty walking and/or swallowing
• dystonia

One or more of the copper tests may be ordered periodically when monitoring is recommended.

A hepatic (liver) copper test may be ordered to further investigate copper storage when copper and caeruloplasmin results are abnormal or equivocal.

What does the result mean?

Copper test results must be evaluated in context and are usually compared with caeruloplasmin levels. Abnormal copper results are not diagnostic of a specific condition - they indicate the need for further investigation. Interpretation can be complicated by the fact that caeruloplasmin is an acute phase reactant - it may be elevated whenever inflammation or severe infections are present. Both caeruloplasmin and copper are also increased during pregnancy and with oestrogen and oral contraceptive use.

Test results may include:

• Low blood copper concentrations along with increased urine copper levels, low caeruloplasmin levels, and increased hepatic copper are typically seen with Wilson disease.
• Increased blood and urine copper concentrations and normal or increased caeruloplasmin levels may indicate exposure to excess copper or may be associated with conditions that decrease copper excretion - such as liver disease. Increased hepatic copper may be present with chronic conditions.
• Decreased blood and urine copper concentrations and decreased caeruloplasmin can indicate a copper deficiency.
• A normal hepatic copper test can indicate that copper metabolism is functioning properly or that the distribution of copper in the liver is uneven and the sample is not representative of the person's condition.

If someone is being treated for excess copper storage with chelators their 24-hour urine copper levels may be high until body copper stores decrease. Eventually, blood copper and 24-hour urine copper concentrations should normalise.

If someone is being treated for a condition related to copper deficiency and their caeruloplasmin and total copper concentrations begin to rise, the condition is likely to be responding to the treatment.

Is there anything else I should know?

Medications such as oestrogens, oral contraceptive pills, carbamazepine and phenobarbital can increase blood copper levels. They may also be elevated with rheumatoid arthritis and with some cancers, and decreased with a variety of conditions associated with malabsorption such as cystic fibrosis.

Total serum copper concentrations are normally low at birth, rise over the next few years, peak, and then decline slightly to a relatively stable level.

Care must be taken especially with a 24-hour urine sample, not to contaminate the sample with an external source of copper. Talk to your doctor and the person who gives you the urine collection bottle about necessary precautions. If a urine or blood copper test result is higher than expected you may be asked to repeat the test to confirm the findings.

Common questions

• Should everyone's copper metabolism be evaluated?

General screening for copper concentrations is not recommended or necessary. Many people with conditions not associated with copper such as infections or inflammation may have temporarily increased concentrations.

• Can I choose either a blood (total or free) or urine copper test?

These tests provide complementary information. It is up to you and your doctor to determine which tests are necessary to evaluate your condition.

• What happens if I am exposed to toxic amounts of copper?

Copper poisoning can cause vomiting and diarrhoea and, in some cases lead to liver and kidney damage. You should talk to your doctor if you think that you have been exposed.

• Should I be taking copper supplements or trying to get more copper in my diet?

In most cases, a regular diet satisfies the body's requirements for copper. Talk to your doctor before taking any supplements or changing your diet.

More information

RCPA Manual: Copper

RCPA Manual: Copper - urine