Test Id : NMH1D
N-Methylhistamine, 24 Hour, 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 as a part of a profile
Monitoring therapeutic progress in conditions that are associated with secondary, localized, low-grade persistent, mast-cell proliferation and activation such as interstitial cystitis
Method Name
A short description of the method used to perform the test
Only orderable as part of a profile. For more information see NMH24 / N-Methylhistamine, 24 Hour, Urine.
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
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
Specimen Type
Describes the specimen type validated for testing
Urine
Ordering Guidance
Random urine collection is preferred for patients with episodic symptoms, eg, in the context of allergic reactions, brought on by specific environmental factors; order NMHR / N-Methylhistamine, Random, Urine.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Only orderable as part of a profile. For more information see NMH24 / N-Methylhistamine, 24 Hour, Urine.
Patient Preparation: Patient must not be taking monoamine oxidase inhibitors (MAOIs) or aminoguanidine as these medications increase N-methylhistamine (NMH) levels.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Container/Tube: Plastic, 5-mL tube
Specimen Volume: 5 mL
Collection Instructions:
1. Collect urine for 24 hours.
2. No preservative.
3. Aliquot into plastic tube and send at refrigerate temperature.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
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 | |
| Ambient | 28 days | ||
| Frozen | 28 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 as a part of a profile
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, particularly 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.
Definitive 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 (23BPT / 2,3-Dinor 11 Beta-Prostaglandin F2 Alpha, 24 Hour, 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.
Only orderable as part of a profile. For more information see NMH24 / N-Methylhistamine, 24 Hour, Urine.
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 years, 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;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, et al. Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Derm. 1996;35(4):556-558
6. Divekar R, Butterfield J. Urinary 11b-PGF2a and N-methyl histamine correlate with bone marrow biopsy findings in mast cell disorders. Allergy. 2015;70(10):1230-1238. doi:10.1111/all.1266
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 Pract. 2020;8(8):2533-2541. doi:10.1016/j.jaip.2020.02.021
Method Description
Describes how the test is performed and provides a method-specific reference
N-methylhistamine (NMH) is removed from urine using solid phase extraction. The eluate is analyzed using liquid chromatography/tandem mass spectrometry and quantified using a stable isotope labeled internal standard, d3-NMH. NMH and d3-NMH are detected in multiple reaction monitoring mode using the specific transitions for m/z 126 to m/z 109, and m/z 129 to m/z 112, respectively.(Unpublished Mayo method)
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, 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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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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. It 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.
CPT codes are provided by the performing laboratory.
82542
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 |
|---|---|---|
| NMH1D | N-Methylhistamine, 24 Hr, U | 44340-8 |
| 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.
|
|---|---|---|
| 605159 | N-Methylhistamine, 24 Hr | 44340-8 |