Methylated catecholamine metabolites for diagnosis of neuroblastoma

Abstract

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures.

In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity.

“…Using a sensitive HPLC technique similar to ours, Candito et al (29) reported mean plasma concentrations of epinephrine of 135Ϯ36 pg/ml (SE) (range 18-568 pg/ml) in children studied in the same resting conditions as the present subjects. These values are comparable to the basal epinephrine values in our nonobese children (150Ϯ22 pg/ml).…”

“…Plasma concentrations of adolescents in the resting state measured with a radioenzymatic method were lower: 288Ϯ20 pg/ml (31) and 285Ϯ30 pg/ml (32). Our mean norepinephrine value in nonobese children (1,507Ϯ234 pg/ml) are at the upper limit of the normal range of HPLC measurements (29). These relatively high norepinephrine values in normal children were possibly due to a slight degree of unseen agitation in a subset of resting lean children, as discussed (29).…”

“…Our mean norepinephrine value in nonobese children (1,507Ϯ234 pg/ml) are at the upper limit of the normal range of HPLC measurements (29). These relatively high norepinephrine values in normal children were possibly due to a slight degree of unseen agitation in a subset of resting lean children, as discussed (29). In those normal children with the highest basal norepinephrine values, however, basal lipolysis and heart rate were not increased, nor were responses of these variables to epinephrine infusion decreased.…”

“…For additional comparison, other studies of basal plasma epinephrine concentrations in normal adolescents yielded mean values of 440 pg/ml using HPLC (30) and 30-41 pg/ml using a radioenzymatic method (31,32). Mean resting norepinephrine values measured with HPLC were 442Ϯ91 pg/ml (SE) (range 85-1,923 pg/ml) (29) and 580 pg/ml (30) in normal children. Plasma concentrations of adolescents in the resting state measured with a radioenzymatic method were lower: 288Ϯ20 pg/ml (31) and 285Ϯ30 pg/ml (32).…”

Age-related medical decision limits for urinary free (unconjugated) metadrenalines, catecholamines and metabolites in random urine specimens from children

“…Although there was only a limited amount of data for urinary f3MT, this latter test exhibited a very high sensitivity for detection of neuroblastoma as suggested previously. 9 The real advantage of the fNMA test was in the detection of phaeochromocytoma or paraganglioma since this was positive in all 11 cases presenting in childhood (Table 6). Urinary NA showed marginally less sensitivity than fNMA in this small cohort.…”