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Pediatric total fractionated metanephrines: age-related reference intervals in spot urine
Laura Roli1, Agnese Veronesi2, Maria C DE Santis2
1Department of Laboratory Medicine and Pathology, AUSL of Modena, Modena, Italy - l.roli@ausl.mo.it.
Insights
This study establishes updated reference intervals for urinary metanephrines in children, crucial for diagnosing conditions like pheochromocytoma. The findings show these levels vary significantly with age, necessitating age-specific pediatric reference ranges.
Area of Science:
- Clinical Chemistry
- Pediatric Endocrinology
- Analytical Chemistry
Background:
- Pediatric reference intervals for metanephrines are inconsistent due to varying methodologies.
- Accurate reference intervals are essential for diagnosing neuroendocrine tumors in children.
Purpose of the Study:
- To establish updated pediatric reference intervals for total fractionated metanephrines in spot urine.
- To standardize measurements using a specific commercial extraction kit and HPLC-ED system.
Main Methods:
- Analyzed 452 pediatric urine samples, excluding those with relevant medical conditions.
- Extracted urinary metanephrine, normetanephrine, and 3-methoxytyramine using a commercial kit.
- Quantified analytes via High-Performance Liquid Chromatography with an Electrochemical Detector (HPLC-ED), reporting as analyte-to-creatinine ratios.
Main Results:
- No significant gender-based differences were observed for the three analytes.
- All three metanephrine fractions showed a statistically significant inverse relationship with age.
- Reference intervals were successfully calculated as a function of age.
Conclusions:
- This study provides age-specific pediatric reference intervals for urinary fractionated metanephrines.
- The established intervals are calibrated to a specific analytical system, enhancing laboratory transferability.
Background:
Sparse metanephrines reference intervals in pediatric populations are available and different study designs and technologies/ assays used in these studies lead to hardly transferable data from a laboratory to another. The aim of this study was to update pediatric reference intervals of total fractionated metanephrines in spot urine samples, using a commercial extraction kit run on a specific high-pressure liquid chromatograph coupled with an electrochemical detector.
Methods:
Four hundred and fifty-two spot pediatric urinary samples previously submitted to urinalysis were consecutively included in the study with the exclusion of children's samples with diagnosis or clinical suspicion of paraganglioma/pheochromocytoma, kidney diseases and arterial hypertension. Urinary metanephrine, normetanephrine and 3-methoxytyramine were extracted with ClinRep® HPLC Complete kit and run on HPLC Prominence liquid chromatograph LC-20AT (Shimadzu Italia S.r.l. Milan, Italy) coupled with Decade II electrochemical detector (Antec Scientific, Zoeterwoude, the Nederlands, provided by Alfatech S.r.l., Genoa, Italy). Results were expressed as the ratio analyte-to-creatinine.
Results:
Any of the three analytes required a repartition by gender (metanephrine P=0.27; normetanephrine P=0.90 and 3-methoxytyramine P=0.18). A significant statistically inversely proportional relation with age was found for metanephrine (P<0.0001; ρ=-0.72), normetanephrine (P<0.0001; ρ=-0.75) and 3-methoxytyramine (P<0.0001; ρ=-0.83). Reference intervals were calculated as function of age.
Conclusions:
This study provides pediatric reference intervals for urinary fractionated total metanephrines in spot urine calibrated on a specific instrumentation and extraction commercial kit.
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