Test ID: NMHIN
N-Methylhistamine, Urine
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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
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 |
|---|---|---|---|
| NMH | N-Methylhistamine, U | No | Yes |
| NCTU | Creatinine Concentration | No | Yes |
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
NMH/21589: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
NCTU/21600: Enzymatic Colorimetric Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Histamine Metabolites
Urinary N-Methylhistamine
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Plastic, 6-mL tube (Supply T465)
Specimen Volume: 5 mL
Collection Instructions:
1. Collect urine for 24 hours.
2. No preservative.
Additional Information:
1. 24-Hour volume is required.
2. 24-Hour collection is preferred, but random specimen is also acceptable.
3. See Urine Preservatives in Special Instructions for multiple collections.
Urine Preservative Collection Options
| Ambient | Yes |
| Refrigerated | Preferred |
| Frozen | Yes |
| 6N HCl | Yes |
| 50% Acetic Acid | Yes |
| Na2CO3 | Yes |
| Toluene | Yes |
| 6N HNO3 | Yes |
| Boric Acid | Yes |
| Thymol | Yes |
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Urine | Refrigerated (preferred) | 8 days |
| Frozen | 14 days | |
| Ambient | 24 hours |
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 (BPG2/81425 11 Beta-Prostaglandin F(2) Alpha, Urine), and tryptase, alpha or beta (TRYPT/81608 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 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 spot-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
Individuals who are taking monoamine oxidase inhibitors (MAOIs) or aminoguanidine will have increased levels of N-methylhistamine (NMH); results from patients on MAOIs are uninterpretable.
While an average North American diet has no effect on urinary NMH levels, mild elevations (around 30%) may be observed on very histamine-rich diets. This problem is more pronounced if spot urine specimens rather than 24-hour urine specimens are used and the spot urine specimen is collected following a histamine-rich meal.
NMH may be lowered in individuals who are receiving drugs that inhibit diamine oxidase.
NMH levels may be depressed in individuals who have a polymorphism in the histamine-N-methyl transferase gene, which encodes the enzyme that catalyzes NMH formation. This polymorphism results in an amino acid change that decreases the rate of NMH synthesis.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Roberts LJ II, Oates JA: Disorders of vasodilator hormones: the carcinoid syndrome and mastocytosis. In Williams Textbook of Endocrinology. Eighth edition. Edited by JD Wilson, DW Foster. Philadelphia, WB Saunders Company, 1992, pp 1625-1634
2. Akin C, Metcalfe DD: Mastocytosis. In Allergic Skin Disease: A Multidisciplinary Approach. Edited by DYM Leung, MW Greaves. New York. Marcel Dekker, Inc., 2000, pp 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
Method Description Describes how the test is performed and provides a method-specific reference
N-methylhistamine (NMH) is extracted from urine using solid-phase extraction. The elute is analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) 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;721[1]:135-140)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday, Thursday; 1 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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 The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83789
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| NCTU_ | Creatinine Conc | 2161-8 |
| 21589 | N-Methylhistamine, U | 44340-8 |
| TM73 | Collection Duration | 13362-9 |
| VL63 | Urine Volume | 28009-9 |
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