26026 N-Methylhistamine, Urine (NMHIN)

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.

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.

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.

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 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.