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TEST ID NMHR N-Methylhistamine, Random, Urine

Reporting Name

N-Methylhistamine, Random, U

Specimen Type

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. order 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


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

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Container/Tube: Plastic vial

Specimen Volume: 5 mL

Collection Instructions:

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

2. No preservative.


Specimen Minimum Volume

3 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  14 days

Method Name

NMHR1: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

CRETR: Enzymatic Colorimetric Assay

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Reference Values

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

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

>16 years: 30-200 mcg/g creatinine

Day(s) Performed

Monday, Wednesday, Friday

Report Available

3 to 7 days

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

82542

82570

Useful For

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

Test ID Reporting Name Available Separately Always Performed
NMHR1 N-Methylhistamine, Random No Yes
CRETR Creatinine, Random, U No Yes

Clinical Information

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, urticarial 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 adults, the disease is progressive. Systemic mastocytosis may or may not be accompanied by UP.(1,2) 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 systemic mastocytosis is made by bone marrow biopsy; however, patients with systemic mastocytosis also usually exhibit elevated levels of NMH.(1-5) Other biochemical markers include 11-beta prostaglandin F2 alpha, a metabolite of prostaglandin D2 (23BPR / 2,3-Dinor 11 Beta-Prostaglandin F2 Alpha, Random, Urine) and tryptase, alpha or beta (TRYPT / Tryptase, Serum). Histamine in blood or urine is also sometimes measured, but it generally has less diagnostic value than NMH measurement in urine, in particular if measurements in blood are not undertaken during a spell.

Cautions

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.

Method Description

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)

 

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)