Test Catalog

Test Id : FET

Iron, Liver Tissue

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of hemochromatosis using liver tissue specimens

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Hereditary Hemochromatosis Algorithm in Special Instructions

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Iron, Liver Ts

Aliases
Lists additional common names for a test, as an aid in searching

Fe (Iron)

Hemochromatosis

Hepatic Iron Concentration

Hepatic Iron Index

Iron (Fe)

Iron, Tissue Liver

Metals, Tissue

Quantitative Iron

Total Iron, Liver Tissue

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Hereditary Hemochromatosis Algorithm in Special Instructions

Specimen Type
Describes the specimen type validated for testing

Liver Tissue

Necessary Information

Patient's date of birth is required to calculate iron index.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Metal Free Specimen Vial (T173)

Container/Tube:

Preferred: Mayo metal-free specimen vial (blue label)

Acceptable: Paraffin block, if not more than 1 or 2 cuts have been made to it for slides

Specimen Volume: 2 mg

Collection Instructions:

1. Two 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.

Additional Information: Paraffin blocks will be returned 3 days after analysis.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2 cm (22-gauge needle)

1 cm (18-gauge needle)

2 mm x 2 mm (punch) 0.3 mg by dry weight

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Liver Tissue Refrigerated (preferred)
Ambient
Frozen

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of hemochromatosis using liver tissue specimens

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Hereditary Hemochromatosis Algorithm in Special Instructions

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hemosiderosis is the condition of excessive iron accumulation in tissues. Liver is the first organ affected in iron-overload diseases. Transient increases in iron first appear in Kupffer cells. This finding is commonly related to sideroblastic anemia, excessive iron consumption, or chronic alcohol ingestion. Persistent hemosiderosis, as seen in hemochromatosis, causes iron accumulation in hepatocytes, and is usually concentrated in biliary cells.

 

Hereditary hemochromatosis is an autosomal recessive disease with estimated prevalence in the population of 2 in 1,000 in Caucasians, with lower incidence in other races. The gene responsible for hereditary hemochromatosis (HFE) is located on chromosome 6; the majority of hereditary hemochromatosis patients have variants in this HFE gene. Hereditary hemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues that typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disease if left untreated and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important.

 

Screening for hemochromatosis is best done by measuring serum iron and transferrin saturation (FEC / Iron and Total Iron-Binding Capacity, Serum). If the serum iron concentration is above 175 mcg/dL and the transferrin saturation is above 55%, analysis of serum ferritin concentration (FERR / Ferritin, Serum) is indicated. A ferritin concentration above 400 ng/mL is suggestive of hemochromatosis, but also can indicate other forms of hepatocyte injury such as alcoholic or viral hepatitis, or other inflammatory disorders involving the liver. HFE analysis (HFE / Hemochromatosis HFE Gene Analysis, Blood) may be used to confirm the clinical diagnosis of hemochromatosis, to diagnose hemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals who have a family history of hemochromatosis. The alleles evaluated by HFE gene analysis are evident in approximately 80% of patients with hemochromatosis; a negative report for HFE gene does not rule-out hemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated.

 

Diagnosis of hemochromatosis may also be based on biochemical analysis and histologic examination of a liver biopsy. In this assay, results are reported as the hepatic iron index (HII) and dry weight of iron. The HII is considered the "gold standard" for diagnosis of hemochromatosis. This test is appropriate when:

-Serum iron is above 160 mcg/dL

-Transferrin saturation is above 55%

-Ferritin is above 400 ng/mL in males or above 200 ng/mL in females

-HFE gene test is negative for HFE variants

 

See Hereditary Hemochromatosis Algorithm in Special Instructions

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.

IRON

Males: 200-2,400 mcg/g dry weight

Females: 200-1,800 mcg/g dry weight

 

IRON INDEX

Reference values have not been established for patients that are <13 years of age.

<1.0 mcmol/g/year (> or =13 years)

Interpretation
Provides information to assist in interpretation of the test results

A hepatic iron concentration above 10,000 mcg/g dry weight is diagnostic for hemochromatosis.

 

Hepatic iron concentrations above 3,000 mcg/g are seen when there is iron overload without cellular injury and cirrhosis. Hepatic iron concentrations greater than the reference range are associated with hemosiderosis, thalassemia, and sideroblastic anemia. Some patients with hepatitis or cirrhosis without significant fibrosis will have hepatic iron concentrations at the top end of normal or just slightly above the normal range.

 

Iron accumulates in the liver normally with aging. The hepatic iron index (HII) normalizes hepatic iron concentration for age. The HII is calculated from the hepatic iron concentration by converting the concentration from mcg/g to mcmol/g dry weight and dividing by years of age. The normal range for HII is less than 1.0.

-Patients with homozygous hemochromatosis have an HII above 1.9.

-Patients with heterozygous hemochromatosis often have an HII ranging from 1.0 to 1.9.

-Patients with hepatitis and alcoholic cirrhosis usually have an HII below 1.0, although a small percentage of patients with alcoholic cirrhosis have an HII in the range of 1.0 to 1.9.

-Patients with hemochromatosis who have been successfully treated with phlebotomy will have an HII below 1.0.

 

Liver specimens collected from patients with cirrhosis containing a high degree of fibrosis have results near the low end of the reference range, even though they will show significant iron staining in hepatocytes. While it is true that iron accumulates in hepatocytes in advanced alcoholic cirrhosis with fibrosis, there are relatively few hepatocytes compared to other inert (fibrotic) tissue, so the quantitative iron determination, which is expressed as mcg of iron per gram of dry weight tissues, yields a low result. Histologic examination of all tissue specimens should be performed to facilitate correct interpretation. When structural heterogeneity is apparent histologically, variation in measured iron should be anticipated. We have observed, in approximately 2% of cases, a high degree of hepatic heterogeneity that makes quantitation highly variable.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Formalin-fixed, paraffin-embedded tissue can be used when histologic examination (including iron stains) is requested, in addition to the hepatic iron concentration and calculated hepatic iron index. However, fresh or frozen tissue is preferred.

 

Paraffin blocks from which many slides have been previously cut often appear to contain sufficient quantity of tissue, however, the specimen is often very thin and less than 2 mg in weight.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Brandhagen DJ, Fairbanks VF, Baldus W: Recognition and management of hereditary hemochromatosis. Am Fam Physician. 2002;65:853-860, 865-866

2. Summers KM, Halliday JW, Powell LW: Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index. Hepatology. 1990;12:20-25

3. Ludwig J, Batts KP, Moyer TP, et al: Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm. Mayo Clin Proc. 1993;68:263-267

4. Pietrangelo A: Hemochromatosis: an endocrine liver disease. Hepatology. 2007;46:1291-1301

5. Ashley EA, Butte AJ, Wheeler MT, et al: Clinical assessment incorporating a personal genome. Lancet. 2010;375:1525-1535

6. McLaren CE, Barton JC, Eckfeldt JH, et al: Heritability of serum iron measures in the hemochromatosis and iron overload screening (HEIRS) family study. Am J Hematol. 2010;85:101-105

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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 iron concentration is analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) using gallium (Ga) as an internal standard and a aqueous acidic calibration.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

60 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) 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 US 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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83540

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports