Reference intervals for deconjugated urine metanephrines by Bhattacharya analysis

Area of Science:

• Endocrinology
• Clinical Chemistry
• Diagnostic Medicine

Background:

• Urine metanephrines are crucial for screening phaeochromocytoma or paraganglioma (PPGL).
• Existing reference intervals (RI) lack age and sex stratification, leading to high false positive rates, especially in hypertensive patients.
• This study addresses the need for refined RI in a screening population.

Purpose of the Study:

• To determine age and sex-stratified reference intervals (RI) for urine metanephrine and normetanephrine excretion.
• To establish stratified RI for metanephrine/creatinine and normetanephrine/creatinine ratios.
• To improve the diagnostic accuracy of PPGL screening.

Main Methods:

• Analysis of 24-h deconjugated urine metanephrines from 8221 patients (2936 males, 5285 females) between 2010 and 2022.
• Utilized liquid chromatography with electrochemical detection (LC-ECD) and tandem mass spectrometry (LC-MS/MS).
• Applied Bhattacharya analysis on log-transformed data to derive age and sex-stratified RI.

Main Results:

• Normetanephrine excretion increases with age, with distinct RI for males and females across different age groups (18-30, 30-40, 40+ years).
• Metanephrine excretion remained consistent across adulthood, with specific RI for males and females (18+ years).
• Normetanephrine/creatinine and metanephrine/creatinine ratios increased with age, particularly after early adulthood, with higher ratios observed in females.

Conclusions:

• Established age and sex-stratified RI for urine metanephrine and normetanephrine, and their creatinine ratios.
• These new RI are expected to significantly reduce false positive results in PPGL screening.
• The findings will aid in more accurate identification of patients with PPGL.