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Age-specific pediatric reference intervals for plasma free normetanephrine, metanephrine, 3-methoxytyramine and
Mirko Peitzsch1, Anastasios Mangelis1, Graeme Eisenhofer2
1Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Insights
Establishing age-specific reference intervals for catecholamine metabolites is crucial for diagnosing neuroblastoma in children. These new intervals account for significant developmental changes in metabolite levels during infancy and childhood.
Area of Science:
- Biochemistry
- Pediatric Endocrinology
- Oncology
Background:
- Establishing reliable reference intervals for biochemical tests in pediatric patients presents challenges.
- Accurate reference intervals are essential for diagnosing conditions like neuroblastoma, especially in young children.
Purpose of the Study:
- To establish age-specific, continuous reference intervals for catecholamine O-methylated metabolites in children.
- To improve the accuracy of biochemical testing for catecholamine-producing tumors in pediatric populations.
Main Methods:
- Plasma concentrations of 3-methoxytyramine, normetanephrine, metanephrine, and 3-O-methyldopa were measured.
- Liquid chromatography tandem mass spectrometry was used for analysis.
- The study included 533 children aged from 2 days to 18 years.
Main Results:
- Plasma concentrations of normetanephrine, 3-methoxytyramine, and 3-O-methyldopa were elevated in neonates and young infants, decreasing significantly with age.
- Metanephrine concentrations showed a reciprocal pattern, being lower in infants under one year compared to older children.
- These findings highlight significant developmental shifts in catecholamine metabolite levels during early childhood.
Conclusions:
- Reciprocal changes in plasma catecholamine metabolites during early childhood indicate developmental alterations in chromaffin tissues.
- Consideration of these developmental changes is vital for establishing accurate pediatric reference intervals.
- The developed reference intervals enhance biochemical testing for catecholamine-producing tumors in young children.
Background:
Availability of appropriately established reference intervals for biochemical tests can be troublesome in pediatrics. Here we establish age-specific continuous reference intervals for catecholamine O-methylated metabolites in children evaluated for catecholamine producing tumors, particularly younger children with suspected neuroblastoma.
Methods:
Plasma concentrations of 3-methoxytyramine, normetanephrine, metanephrine, and 3-O-methyldopa were analyzed by liquid chromatography tandem mass spectrometry in 533 children aged 2 days to 18 years.
Results:
Concentrations of plasma free normetanephrine, 3-methoxytyramine and 3-O-methyldopa were higher in neonates up until six months of age, but thereafter declined steeply to levels after one year that were <38% those of neonatal concentrations and to further lower concentrations in teenagers that were <23% those in neonates. In contrast, concentrations of plasma free metanephrine showed a reciprocal pattern with 50% lower concentrations in infants below one year compared to later in childhood.
Conclusion:
The dynamic reciprocal changes in plasma concentrations of normetanephrine, 3-methoxytyramine and 3-O-methyldopa compared to metanephrine during early childhood suggest underlying developmental changes in extra-adrenal and adrenal chromaffin tissue that must be considered for pediatric reference intervals, particularly in infants. With such reference intervals at hand, biochemical testing for catecholamine producing tumors in young children is substantially improved.
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