1-Methylhistamine Histamine Metabolites Urinary N-Methylhistamine
N-Methylhistamine, 24 Hr, U
Creatinine, 24 Hr, U
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 24-hour urine collection specimens
Monitoring therapeutic progress in conditions that are associated with secondary, localized, low-grade persistent, mast-cell proliferation and activation such as interstitial cystitis
Patient must not be taking monoamine oxidase inhibitors (MAOIs) or aminoguanidine as these medications increase N-methylhistamine (NMH) levels.
1. Collect urine for 24 hours
2. No preservative
3. Aliquot into plastic tube and send at refrigerate temperature.
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.
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-methyl transferase 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.
NMH1D: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
CRT24: Enzymatic Colorimetric Assay
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. 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. Other biochemical markers include 11-beta prostaglandin F(2) alpha, a metabolite of prostaglandin D2 (23BPG / 2,3-Dinor-11Beta-Prostaglandin F2 Alpha, Urine), and alpha or beta tryptase (TRYPT / Tryptase, Serum).
0-5 years: 120-510 mcg/g creatinine
6-16 years: 70-330 mcg/g creatinine
>16 years: 30-200 mcg/g creatinine
Males: 930-2955 mg/24 hours
Females: 603-1783 mg/24 hours
Reference values have not been established for patients who are less than 18 years of age.
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.