Copper, Liver Tissue
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Diagnosing Wilson disease and primary biliary cirrhosis
Dynamic Reaction Cell-Inductively Coupled Plasma-Mass Spectrometry (DRC-ICP-MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Copper, Liver Ts
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Mayo metal-free specimen vial (blue label) (Supply T173)
Acceptable: Paraffin block if no more than 1 or 2 cuts have been made to it for slides
Specimen Volume: 2 mg
1. 2 mg of liver tissue is required. This is typically a piece of tissue from a 22-gauge needle biopsy at least 2 cm long. If an 18-gauge needle is used, the tissue must be at least 1 cm in length.
2. Any specimen vial other than a Mayo metal-free vial used should be plastic, leached with 10% nitric acid for 2 days, rinsed with redistilled water, and dried in clean air.
1. If tissue is other than liver tissue, see MSCM / Miscellaneous Metals Testing.
2. Paraffin blocks will be returned 3 days after analysis.
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
2 cm (22-gauge needle), 1 cm (18-gauge needle), or 2 mm x 2 mm (punch)
0.3 mg by dry weight
0.3 mg by dry weight
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Liver Tissue||Refrigerated (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Homeostatic regulation of copper metabolism is very complex. The liver is the key organ to facilitate copper storage and incorporation of copper into the transport protein ceruloplasmin. Intestinal absorption and biliary excretion also play major roles in the regulation of copper homeostasis.
Abnormal copper metabolism is associated with liver disease. Elevated serum copper concentrations are seen in portal cirrhosis, biliary tract disease, and hepatitis, probably because excess copper that would normally be excreted in the bile is retained in circulation. In primary biliary cirrhosis, ceruloplasmin is high, resulting in high serum copper. Lesser elevations of hepatic copper are found in chronic copper poisoning, obstructive jaundice, and certain cases of hepatic cirrhosis. Reduced serum copper concentration is typical of Wilson disease (hepatolenticular degeneration). Wilson disease is characterized by liver disease, neurologic abnormalities, and psychiatric disturbances. Kayser-Fleischer rings are normally present and urinary copper excretion is increased, while serum copper and ceruloplasmin are low.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
10-35 mcg/g dry weight
>1,000 mcg/g dry weight: VERY HIGH
This finding is strongly suggestive of Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.
250-1,000 mcg/g dry weight: HIGH
This finding is suggestive of possible Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.
35-250 mcg/g dry weight: HIGH
Excessive copper at this level can be associated with cholestatic liver disease, such as primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and familial cholestatic syndrome. Heterozygous carriers for Wilson disease occasionally have modestly elevated values, but rarely higher than 125 mcg/g of dry weight. In general, the liver copper content is higher than 250 mcg/g dried tissue in patients with Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.
The constellation of symptoms associated with Wilson disease (WD), which includes Kayser-Fleischer rings, behavior changes, and liver disease, is commonly associated with liver copper concentration >250 mcg/g dry weight.
>1,000 mcg/g dry weight: VERY HIGH. This finding is virtually diagnostic of WD; such patients should be showing all the signs and symptoms of WD.
250 mcg/g dry weight to 1,000 mcg/g dry weight: HIGH. This finding is suggestive of WD unless signs and symptoms, supporting histology, and other biochemical results (low serum ceruloplasmin, low serum copper, and high urine copper) are not evident.
35 mcg/g dry weight to 250 mcg/g dry weight: HIGH. Excessive copper at this level can be associated with cholestatic liver disease, such as primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and familial cholestatic syndrome. The heterozygous carriers for WD occasionally have modestly elevated values, but rarely higher than 125 mcg/g of dry weight. In general, the liver copper content is higher than 250 mcg/g dried tissue in WD patients.
In patients with elevated levels of copper without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for WD (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is available at Mayo Clinic.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Specimen handling should be minimized.
Elevated copper levels without supporting histology or other biochemical test results should instigate an investigation into whether the specimen has been contaminated.
A minimum tissue dry weight of 0.3 mg is required for analysis. This is the equivalent of a piece of tissue from a 22-gauge needle approximately 0.5 cm long, or approximately 0.3 cm in length when taken with an 18-gauge needle. Since the specimen must be manipulated during analysis, more than the minimal amount described in the previous sentence must be submitted for analysis.
Paraffin blocks that have been cut for slides may be contaminated if the microtome was previously used to cut specimens that had been fixed with a copper-containing solution. Many fixatives, such as Hollandes, contain high levels of copper. Any object that has been exposed to these fixatives (eg, cutting boards, towels, containers, utensils) that comes into contact with the tissue can potentially contaminate the specimen. Rinsing and washing will not remove the copper contaminant. Therefore, submission of fresh-frozen, unfixed tissue is strongly recommended.
Gadolinium is known to interfere with most metals tests. If gadolinium-containing contrast media has been administered a specimen should not be collected for 96 hours.
See Improving Test Success in Iron Liver Tissue Specimens in Publications.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Korman J, Volenberg I, Balko J, et al: Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology 2008 Oct;48(4):1167-1174
2. Roberts EA, Schlisky ML: Diagnosis and Treatment of Wilson Disease: AASLD Practice Guidelines. Hepatology 2008;47:2089-2111
3. de Bie P, Muller P, Wijmenga C, Klomp LW: Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2007 November;44(11):673-688
4. Merle U, Schaefer M, Ferenci P, Stremmel W: Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut 2007;56:115-120
Method Description Describes how the test is performed and provides a method-specific reference
After digestion of the liver tissue with nitric acid and hydrogen peroxide, the digest is diluted and tissue copper concentration is determined using an inductively coupled plasma-mass spectrometer in dynamic reaction cell mode. Calibrating standards and blanks are diluted with an aqueous acidic diluent containing internal standard(s). Quality control specimens and patient samples are diluted in an identical manner. In turn, all diluted blanks, calibrating standards, quality control specimens, and patient specimens are aspirated into a pneumatic nebulizer and the resulting aerosol directed to the hot plasma discharge by a flow of argon. In the annular plasma the aerosol is vaporized, atomized, then ionized. The ionized gases plus neutral species formed in the annular plasma space are aspirated from the plasma through an orifice into a quadrupole mass spectrometer. The mass range from 1 to 263 amu is rapidly scanned multiple times and ion counts tabulated for each mass of interest. Instrument response is defined by the linear relationship of analyte concentration vs. ion count ratio (analyte ion count/internal standard ion count). Analyte concentrations are derived by reading the ion count ratio for each mass of interest and determining the concentration from the response line. Results are reported in mcg copper/g dry weight of tissue.(Bush VJ, Moyer TP, Batts KP, Parisi JE: Essential and toxic element concentrations in fresh and formalin-fixed human autopsy tissues. Clin Chem 1995:41;284-294; Hanley MM: Copper and iron liver tissue analysis: a comprehensive platform comparison [Abstract 1600-7P]. PittCon 2008, New Orleans, Louisiana, March 2-7, 2008)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 11 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Fresh tissue: 1 month Block: Returned to client after 3 days
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|8687||Copper, Liver Ts||8198-4|