Test Catalog

Test Id : LTE4

Leukotriene E4, Urine

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

Evaluating patients suspected of having systemic mastocytosis

 

Identification of aspirin sensitivity in patient respiratory diagnoses

Highlights

Urinary leukotriene (LTE4) is elevated in the urine of patients with systemic mastocytosis (SM).

 

When this test is used in combination with 2,3-dinor-11beta-prostaglandin F2 alpha (2,3 BPG) and N-methyl histamine analyses, the sensitivity for SM detection increases to 90%with a specificity above 60%.

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

When leukotriene E4 testing is performed, urine creatinine will always be performed at no additional charge.

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

LTE4: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

AACT: Enzymatic Colorimetric Assay

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

Leukotriene E4, U

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

Cysteinyl Leukotriene

Mastocytosis

Systemic Mast Cell Activation

Mast Cell Activation Syndrome

LTE4

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

When leukotriene E4 testing is performed, urine creatinine will always be performed at no additional charge.

Specimen Type
Describes the specimen type validated for testing

Urine

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

Submit only 1 of the following specimens:

 

Patient Preparation: Patients taking 5-lipoxygenase inhibitor Zileuton/Zyflo may have decreased concentrations of leukotriene E4 (LTE4) if dosage has not been discontinued for 48 hours. If possible, discontinue for 48 hours before testing.

 

Preferred: 24-hour urine collection

Supplies: Plastic, 5-mL tube (T465)

Specimen Volume: 4 mL

Collection Instructions:

1. Collect urine for 24 hours.

2. Refrigerate specimen during collection, aliquot 4 mL of urine into plastic tube, and send specimen refrigerated.

Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens in Special Instructions for multiple collections.

 

Acceptable: Random collection

Supplies: Plastic, 5-mL tube (T465)

Specimen Volume: 4 mL

Collection Instructions:

1. Collect a random urine specimen. 

2. Refrigerate specimen after collection and send specimen refrigerated or frozen; do not add any preservative.

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

Urine Preservative Collection Options

Note: The addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection.

Ambient

OK

Refrigerate

Preferred

Frozen

OK

50% Acetic Acid

OK

Boric Acid

OK

Diazolidinyl Urea

No

6M Hydrochloric Acid

No

6M Nitric Acid

No

Sodium Carbonate

OK

Thymol

No

Toluene

No

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

1 mL

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
Urine Refrigerated (preferred) 7 days
Frozen 30 days
Ambient 24 hours

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

Evaluating patients suspected of having systemic mastocytosis

 

Identification of aspirin sensitivity in patient respiratory diagnoses

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

When leukotriene E4 testing is performed, urine creatinine will always be performed at no additional charge.

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

Leukotrienes (LT) are eicosanoids generated from arachidonic acid via the 5-lipoxygenase pathway. Leukotriene E4 (LTE4) is the stable end product of this pathway and, therefore, regarded as a biomarker of total cysteinyl leukotriene (cys-LT) production. Assessment of LTE4 in urine allows for noninvasive specimen collection and avoids artifactual formation of LT during phlebotomy. Generation of LTE4 occurs nonspecifically from active mast cells, basophils, eosinophils, and macrophages, and modulated through a variety of mechanisms. Elevated concentrations of LTE4 are associated with inflammatory and accelerated mast cell activation conditions, specifically in patients with systemic mast cell disease.(1)

 

Systemic mastocytosis (SM), or systemic mast cell disease, is a myeloproliferative neoplasm that has infiltrated extracutaneous organs. Release of mast cell inflammatory mediators leads to disease symptoms including those associated with allergic and anaphylactic reactions, while increased mast cell number leads to organ dysfunction. Consensus diagnostic criteria for SM include 1 major criterion: imaging of the multifocal infiltrates; and 4 minor criteria:

1. Identifying morphological features of greater than 25% of mast cells from bone marrow biopsy

2. Detection of the point genetic alteration at codon 816 in the KIT gene

3. CD2 and/or CD25 expression in mast cells

4. Persistently elevated serum tryptase

Diagnosis requires either 1 major plus 1 minor criterion or 3 minor criteria.(2)

 

Measurement of urinary mast cell activation biomarkers can aid in the initial evaluation of suspected cases of systemic mast cell disease, potentially avoiding the need for imaging and bone marrow examination. Patients with SM frequently have elevated urine concentrations of LTE4,(1) N-methylhistamine,(3,4) and 2,3-dinor 11 beta-prostaglandin F2 alpha.(4)

 

Urinary LTE4 has also demonstrated significant utility in patients with asthma and respiratory diseases. In a study of adults with mild to moderate asthma on 5-lipoxygenase inhibitors, urine LTE4 concentrations decreased approximately 40% compared with asthma control subjects, suggesting modest decreases in LTE4 production correlates with clinical improvements in asthma severity.

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.

< or =104 pg/mg creatinine

Interpretation
Provides information to assist in interpretation of the test results

Elevated urinary leukotriene E4 (LTE4) concentrations above 104 pg/mg creatinine are consistent with the diagnosis of systemic mast cell disease when combined with clinical signs and symptoms. Pharmacological treatment with 5-lipoxygenase inhibitors or leukotriene receptor antagonists has been shown to decrease production of LTE4.

 

Urinary LTE4 may be used together with serum tryptase, urinary 2,3-dinor 11beta-prostaglandin F2 alpha, and urinary N-methylhistamine.

 

LTE4 values of 166 pg/mg creatinine were 89% specific for aspirin sensitivity among patients with respiratory diagnoses.

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

Systemic mastocytosis is a heterogenous disease and lack of elevated LTE4 does not exclude the diagnosis of mast cell disease.

 

Increased excretion of LTE4 has also been reported in the following conditions: asthma, eosinophilic pneumonia, respiratory syncytial virus infection, atopic dermatitis, Crohn disease, and rheumatoid arthritis.

 

This assay measures both LTE4 and the 11-trans-LTE4 as markers of mast cell release.

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

1. Divekar R, Hagan J, Rank M, et al: Diagnostic utility of urinary LTE4 in asthma, allergic rhinitis, chronic rhinosinusitis, nasal polyps, and aspirin sensitivity. J Allergy Clin Immunol Pract. 2016;4:665-670

2. Lueke AJ, Meeusen JW, Donato LJ, Gray AV, Butterfield JH, Saenger AK: Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis. Clin Biochem. 2016 Sep;49(13-14):979-982

3. Gotlib J, Pardanani A, Akin C, et al: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013 Mar 28;121(13):2393-2401

4. Heide R, Riezebos P, van Toorenbergen AW, et al: Predictive value of urinary N-methylhistamine for bone marrow involvement in mastocytosis. J Invest Dermatol. 2000;115(3):587

5. Van Gysel D, Oranje AP, Vermeiden I, de Raadt JDL, Mulder PG, van Toorenenbergen AW: Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Dermatol. 1996;35(4):556-558

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

Leukotriene E4 (LTE4) is quantified in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterium-labeled(d5)-LTE4 internal standard and acetonitrile are added to all standards, controls, and specimens that are then positive pressure filtered to remove salts, particulates, and sediment from the urine. Additional sample clean-up is achieved via a mixed mode anion exchange. The LC-MS/MS performs the instrumental analysis. The ratios of the integrated peak areas of LTE4 and its respective internal standard are used to calculate the concentration of the analyte.(Unpublished Mayo method)

 

All LTE4 concentrations are normalized to urine creatinine levels measured using a Roche Cobas enzymatic method. The enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0 03/2019)

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.

Tuesday, 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 7 days

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

14 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.

82542

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