Test Catalog

Test Id : NMHR

N-Methylhistamine, Random, Urine

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

Screening for and monitoring of mastocytosis and disorders of systemic mast-cell activation, such as anaphylaxis and other forms of severe systemic allergic reactions using random urine specimens

 

Monitoring therapeutic progress in conditions that are associated with secondary, localized, low-grade persistent, mast-cell proliferation and activation such as interstitial cystitis

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
NMHR1 N-Methylhistamine, Random No Yes
CRETR Creatinine, Random, U No Yes

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

NMHR1: 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.

Yes

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

N-Methylhistamine, Random, U

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

1-Methylhistamine

Histamine Metabolites

Urinary N-Methylhistamine

NMHR

NMH

N-Methylhistamine

Specimen Type
Describes the specimen type validated for testing

Urine

Ordering Guidance

Patients with chronic mast cell activation often have chronically elevated N-methylhistamine (NMH) levels and will sometimes have intermittent NMH elevations. In these cases, a 24-hour urine collection is preferred. See NMH24 / N-Methylhistamine, 24 Hour, Urine.

 

If ordering this test with 23BPR / 2,3-Dinor 11 Beta-Prostaglandin F2 Alpha, Random, Urine, both tests must be ordered under different order numbers. They cannot share an order number.

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

Patient Preparation: Patient must not be taking monoamine oxidase inhibitors (MAOIs) or aminoguanidine as these medications increase N-methylhistamine (NMH) levels.

Supplies: Aliquot Tube, 5 mL (T465)

Container/Tube: Plastic vial, 5-mL

Specimen Volume: 5 mL

Collection Instructions:

1. Collect a random urine specimen within a few hours of symptom onset.

2. No preservative.

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

3 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) 28 days
Frozen 28 days
Ambient 14 days

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

Screening for and monitoring of mastocytosis and disorders of systemic mast-cell activation, such as anaphylaxis and other forms of severe systemic allergic reactions using random urine specimens

 

Monitoring therapeutic progress in conditions that are associated with secondary, localized, low-grade persistent, mast-cell proliferation and activation such as interstitial cystitis

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

N-methylhistamine (NMH) is the major metabolite of histamine, which is produced by mast cells. Increased histamine production is seen in conditions associated with increased mast-cell activity, such as allergic reactions, but also in mast-cell proliferation disorders, in particular mastocytosis.

 

Mastocytosis is a rare disease. Its most common form, urticaria pigmentosa (UP), affects the skin and is characterized by multiple persistent small reddish-brown lesions that result from infiltration of the skin by mast cells. Systemic mastocytosis is caused by the accumulation of mast cells in other tissues and can affect organs such as the liver, spleen, bone marrow, and small intestine. The mast-cell proliferation in systemic mastocytosis can be either benign or malignant. In children, benign systemic mastocytosis tends to resolve over time, while in most, but not all adults, the disease is progressive. Systemic mastocytosis may or may not be accompanied by UP.(1,3) Patients with UP or systemic mastocytosis can have symptoms ranging from itching, gastrointestinal distress, bone pain, and headaches; to flushing and anaphylactic shock.

 

Diagnosis of mastocytosis is made by bone marrow biopsy; however, patients with systemic mastocytosis usually exhibit elevated levels of NMH.(1-5) Other biochemical markers include 11-beta prostaglandin F(2) alpha, a metabolite of prostaglandin D2 (23BPR / 2,3-Dinor 11 Beta-Prostaglandin F2 Alpha, Random, Urine), and alpha or beta tryptase (TRYPT / Tryptase, Serum).

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.

0-5 years: 120-510 mcg/g creatinine

6-16 years: 70-330 mcg/g creatinine

>16 years: 30-200 mcg/g creatinine

Interpretation
Provides information to assist in interpretation of the test results

Increased concentrations of urinary N-methylhistamine (NMH) are consistent with urticaria pigmentosa (UP), systemic mastocytosis, or mast-cell activation. Because of its longer half-life, urinary NMH measurements have superior sensitivity and specificity than histamine, the parent compound. However, not all patients with systemic mastocytosis or anaphylaxis will exhibit concentrations outside the reference range and healthy individuals may occasionally exhibit values just above the upper limit of normal.

 

The extent of the observed increase in urinary NMH excretion is correlated with the magnitude of mast-cell proliferation and activation, UP patients, or patients with other localized mast-cell proliferation and activation, show usually only mild elevations, while systemic mastocytosis and anaphylaxis tend to be associated with more significant rises in NMH excretion (2-fold or more). There is, however, significant overlap in values between UP and systemic mastocytosis, and urinary NMH measurements should not be relied upon alone in distinguishing localized from systemic disease.

 

Up to 25% variability in random-urine excreted levels may be observed, making 24-hour urine collections preferable for cases with borderline results.

 

Children have higher NMH levels than adults. By the age of 16, adult levels have been reached.

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

While an average North American diet has no effect on urinary N-methylhistamine (NMH) levels, mild elevations (around 30%) may be observed on very histamine-rich diets. This problem is more pronounced if random-urine specimens are used and collected following a histamine-rich meal.

 

NMH levels may be depressed in individuals who have an alteration in the histamine-N-methyltransferase gene (HNMT), which encodes the enzyme that catalyzes NMH formation. This alteration results in an amino acid change that decreases the rate of NMH synthesis.

 

When N-acetylcysteine is administered at levels sufficient to act as an antidote for the treatment of acetaminophen overdose, it may lead to falsely decreased creatinine results.

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

1. Roberts LJ II, Oates JA: Disorders of vasodilator hormones: the carcinoid syndrome and mastocytosis. In: Wilson JD, Foster DW, eds. Williams Textbook of Endocrinology. 8th ed. WB Saunders Company;1992:1625-1634

2. Akin C, Metcalfe DD: Mastocytosis. In: Leung DYM, Greaves MW, eds. Allergic Skin Disease: A Multidisciplinary Approach. Marcel Dekker, Inc.;2000:337-352

3. Keyzer JJ, de Monchy JG, van Doormaal JJ, van Voorst Vader PC: Improved diagnosis of mastocytosis by measurement of urinary histamine metabolites. N Engl J Med. 1983 Dec;309(26):1603-1605

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 Lijster de Raadt J, Mulder PG, van Toorenenbergen AW: Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Derm. 1996;35(4):556-558

6. Divekar R, Butterfield J: Urinary 11beta-PGF2a and N-methyl histamine correlate with bone marrow biopsy findings in mast cell disorders. Allergy. 2015 Oct;70(10):1230-1238. doi: 10.1111/all.12668

7. Butterfield J, Weiler CR: The utility of measuring urinary metabolites of mast cell mediators in systemic mastocytosis and mast cell activation syndrome. J Allergy Clin Immunol Prac. 2020 Mar 3;S2213-2198(20)30181-1. doi: 10.1016/j.jaip.2020.02.021

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

N-methylhistamine is extracted from urine using solid-phase extraction. The elute is analyzed using liquid chromatography-tandem mass spectrometry and quantified using a stable isotope labeled internal standard.(Martens-Lobenhoffer J, Neumann HJ: Determination of 1-methylhistamine and 1-methylimidazole acetic acid in human urine as a tool for the diagnosis of mastocytosis. J Chromatogr B Biomed Sci Appl. 1999 Jan 8;721[1]:135-140; 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. doi: 10.1016/j.clinbiochem.2016.02.007)

 

Creatinine:

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, 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.

3 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

82570

LOINC® Information

Test Id Test Order Name Order LOINC Value
NMHR N-Methylhistamine, Random, U 13781-0
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip

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