Test Catalog

Test Id : RLTE4

Leukotriene E4, Random, Urine

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

An aid to evaluate patients suspected of having systemic mastocytosis using random urine collections


Systemic mastocytosis is a heterogeneous disorder, including N-methylhistamine and 11 beta-prostaglandin F2 alpha analysis along with this test provides a clinical sensitivity is greater than 90% and specificity is greater than 60%.

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
LTE4R Leukotriene E4, Random, U No Yes
CRETR Creatinine, Random, U No Yes

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

LTE4R: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

CRETR: Enzymatic Colorimetric Assay

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


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

Leukotriene E4, Random, U

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

Cysteinyl Leukotriene


Mast Cell Activation Syndrome


Systemic Mast Cell Activation

Specimen Type
Describes the specimen type validated for testing


Ordering Guidance

A 24-hour urine collection is the preferred specimen type. Order TLTE4 / Leukotriene E4, 24 Hour, Urine.

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

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Container/Tube: Plastic vial

Specimen Volume: 5 mL

Collection Instructions:

1. Collect a random urine specimen. 

2. No preservative preferred.

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

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

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

An aid to evaluate patients suspected of having systemic mastocytosis using random urine collections

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 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 is 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 one major criterion: imaging of the multifocal infiltrates; and 4 minor criteria: 1) identifying morphological features of above 25% of mast cells from bone marrow biopsy, 2) detection of the point alteration at codon 816 in the KIT gene, 3) CD2 and/or CD25 expression in mast cells, and 4) persistently elevated serum tryptase. Diagnosis requires either one major plus one 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/or 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 to 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



> or =18 years old: 16-326 mg/dL

Reference values have not been established for patients who are younger than 18 years of age.

Provides information to assist in interpretation of the test results

Elevated urinary leukotriene E4 (LTE4) concentrations greater than 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 11 beta-prostaglandin F2 alpha, and/or urinary N-methyl histamine.

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

Patients taking 5-lipoxygenase inhibitor zileuton/Zyflo may have decreased concentrations of leukotriene E4 (LTE4) if dosage has not been discontinued for 48 hours.


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.


11-trans-LTE4 interferes with the LTE4 analysis.

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 Jul-Aug;4(4):665-670

2. 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

3. Oranje AP, Mulder PGH, Heide R, Tank B, Riezebos P, van Toorenenbergen AW: Urinary N-methylhistamine as an indicator of bone marrow involvement in mastocytosis. Clin Exp Dermatol. 2002 Sep;27(6):502-506. doi: 10.1046/j.1365-2230.2002.01072.x

4. 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 Oct;35(4):556-558

5. 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

6. Roberts LJ II, Sweetman BJ, Lewis RA, Austen KF, Oates JA: Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med. 1980 Dec 11;303(24):1400-1404

Method Description
Describes how the test is performed and provides a method-specific reference

The specimen and an internal standard are assayed by liquid chromatography-tandem mass spectrometry. The analyte is detected by multiple-reaction monitoring.(Unpublished Mayo 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


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, Thursday

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 6 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


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.

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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.



LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
RLTE4 Leukotriene E4, Random, U 33343-5
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
CRETR Creatinine, Random, U 2161-8
603457 Leukotriene E4, Random, U 33343-5

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

Test Update Resources

Change Type Effective Date
New Test 2022-03-01