Improved diagnosis of mastocytosis by measurement of the major urinary metabolite of prostaglandin D2.
Symptoms of mastocytosis have been attributed to the overproduction of both histamine and prostaglandin (PG) D2. Recently, we developed an assay for the major urinary metabolite of PGD2 (PGD-M), 9 alpha,11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid, and demonstrated that urinary excretion of this compound is markedly increased in patients with mastocytosis. It had been shown previously that measurement of the urinary excretion of histamine metabolites provides a more sensitive biochemical diagnostic indicator of systemic mastocytosis than does measurement of unmetabolized histamine. Therefore, we examined the correlation between the urinary excretion of the histamine metabolite, NT-methylhistamine, and PGD-M in urine samples from patients with mastocytosis. Urinary excretion of NT-methylhistamine and PGD-M was measured in 46 urine samples from 17 patients with histologically documented mastocytosis. Both compounds were quantified by mass spectrometry. In all urine collections showing an increase above normal (2 SD above the mean) in the excretion of NT-methylhistamine, the fold increase above normal in the urinary excretion of PGD-M was substantially greater. Further, in some urine samples from four patients whose excretion of NT-methylhistamine was consistently normal, the excretion of PGD-M was increased above normal by as much as 300%. These data indicate that quantification of the urinary excretion of PGD-M is a more sensitive biochemical diagnostic indicator of mastocytosis than is the quantification of NT-methylhistamine.
Morrow
J D
JD
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Guzzo
C
C
Lazarus
G
G
Oates
J A
JA
Roberts
L J
LJ
D000328:Adult; D003404:Creatinine / Q000652:urine; D005260:Female; D006632:Histamine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008297:Male; D008415:Mastocytosis / Q000175:diagnosis* / Q000652:urine; D008875:Middle Aged; D011457:Prostaglandins D / Q000652:urine*; D012016:Reference Values
D011457:Prostaglandins D; C035860:9-hydroxy-11,15-dioxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid; D006632:Histamine; D003404:Creatinine