Ceruloplasmin:
Ceruloplasmin is an acute phase reactant. As such, its concentration goes up rapidly during inflammation. Since most copper is bound to ceruloplasmin, measuring plasma copper is not ideal since levels can rise and fall due to inflammation and not reflect dietary intake. Nevertheless, ceruloplasmin testing is common in laboratories as an indirect measurement of plasma copper.
Increases in serum ceruloplasmin have been reported during pregnancy, in women taking oral contraceptives, in hepatitis, pneumonia, tuberculosis, rheumatoid arthritis, myocardial infarction, various forms of anemia, and many obscure neurological disorders.
The main use of ceruloplasmin testing is as an initial test for Wilson disease. Low concentrations of ceruloplasmin are consistent with Wilson disease and necessitate further investigation to confirm a diagnosis. Follow-up testing can entail urine testing, genetic testing, and liver biopsy.
Total serum copper:
Total serum copper can be measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). A serum copper concentration below the normal range is associated with Wilson disease. Excess use of zinc supplements can also lead to low copper levels (hypocupremia), as zinc competes with copper for absorption.
Serum concentrations above the normal range are seen in primary biliary cirrhosis, primary sclerosing cholangitis, and a variety of other clinical situations.
Urine copper:
Urine copper concentration is increased in Wilson disease due to decreased serum binding of copper to ceruloplasmin or due to genetic deficiencies in cellular metal ion transporters. Thus, one would expect decreased plasma copper and increased urine copper in Wilson disease. Increased urine copper (hypercupricuria) can also be due to hemochromatosis, biliary cirrhosis, thyrotoxicosis, infection, and other acute, chronic, and malignant diseases such as leukemia. Urine copper concentrations are also elevated in patients taking contraceptives or estrogens and during pregnancy.
Low urine copper levels are seen with malnutrition, hypoproteinemia, malabsorption, and nephrotic syndrome.
