Copper 

Updated: Jun 21, 2022
Author: Joshua Sloan, DO; Chief Editor: Daniela Hermelin, MD 

Reference Range

Copper levels can be evaluated to help diagnose several disease processes. These conditions may be monitored by looking at the total copper, the free serum copper, 24-hour urine copper, and liver biopsy copper concentrations. Serum ceruloplasmin is also a valuable test and can be used to determine the free serum copper.

Copper reference ranges are as follows:

  • Free serum copper: 1.6-2.4 μmol/L or 10-15μg/dL[1]

  • Total copper: 10-22 μmol/L or 63.7-140.12 μg/dL[2]

  • Serum ceruloplasmin: 2.83-5.50 μmol/L or 18-35 μg/dL[1]

  • 24-hour urine copper 0.3-0.8 μmol or 20-50 μg[1]

  • Liver copper 0.3-0.8 μmol/g of tissue or 20-50 μg/g of tissue[1]

 

Interpretation

Normal copper values mean that the individual has normal physiology, absorption, excretion, and dietary intake of copper.

Copper is found in many food sources such as seeds, organ meats, nuts, seafood, and liver.[3] Furthermore, copper is also found in the water supply.[3, 4] Regarding average daily consumption from food, US men and women over age 20 years have copper intakes of 1400 mcg and 1100 mcg, respectively.[5]  With a wide variety of dietary sources, becoming copper deficient is difficult.[6]

However, copper deficiency may occur due to malabsorption, primarily in the duodenum, where most copper is absorbed. Other conditions that can cause a low copper level can be nephrotic syndrome and Menkes disease. Overcorrection of the copper level in the treatment of Wilson disease may also result in a copper deficiency.[1]

Conversely, a high value of total copper may indicate copper toxicity from ingesting too much copper, or, as is more common in infants, poor excretion secondary to underdeveloped biliary systems.[3] In the case of Wilson disease, liver biopsy shows high levels of copper and is considered the criterion standard for diagnosis. Additionally, elevated levels of urinary copper collected with the 24-hour urine study may also indicate a positive diagnosis of Wilson disease. Low levels of serum ceruloplasmin and serum copper are common findings in Wilson disease.

Low levels of serum copper and serum ceruloplasmin may also suggest Menkes disease. They may also indicate a dietary insufficiency; however, this is unlikely given the surplus of copper found in food and water. Low levels of copper seen on liver biopsy and 24-hour urine may also point a clinician to the diagnosis of Menkes disease or copper deficiency.[7]

A retrospective study by Ngwanou et al indicated that while 24-hour urinary copper excretion (UCE) can be a useful tool in monitoring children with Wilson disease during chelation therapy, exchangeable copper can also be used to assess the disorder during such treatment. The median exchangeable copper level fell from 1.01 μmol/L at diagnosis to 0.38 μmol/L after 12-18 months of chelation therapy, with the value then stabilizing, while 24-hour UCE showed a similar pattern, dropping significantly in the first year and then stabilizing. Patients in the study were under age 18 years.[8]

 

Collection and Panels

Serum copper levels may be collected at any time during the day and should be drawn into a dark blue–topped tube. This tube has a sodium EDTA additive and is used for evaluating trace metals in the blood.

The ceruloplasmin may also be drawn at any time during the day and should be drawn in a red-topped tube. The serum is separated by centrifugation from the red blood cells and analyzed.

With regards to liver biopsy, the patient should not eat (NPO) after midnight the night prior to the procedure. Additionally, coagulation studies (PT/PTT/INR) should be drawn and evaluated prior to the procedure to evaluate the risk of bleeding. As with many procedures, the risk of bleeding, infection, and perforation of nearby organs exists.[9] The biopsy should be performed transcutaneously, and a core of tissue should be obtained and placed in a container that does not have any copper components.[10] The sample should be dried and frozen overnight for shipment to the lab.[10] The liver biopsy should be sent for a copper assay, which quantifies the amount of copper and is reported in either μmol/g of tissue or μg/g of tissue.[1, 10]

The 24-hour urine should be collected after the first urination upon waking, which is not voided into the collection device. Afterwards, the patient should be instructed to urinate entirely into the collection device provided. The following morning, the first urination attempt should be collected and is the last quantity collected for the study.[11] The collection device used is the same that is used for other 24-hour urine studies.