Efficacy of Single‐voided Urine Metanephrine and Normetanephrine Assay for Diagnosing Pheochromocytoma

Abstract

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection is not convenient for outpatients. Since 1987 we have utilized "spot" urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every-3-hour urine samples, which were accumulated and then measured as a 24-hour urinary specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/- 9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248, median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean 133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.

Measurement of catecholamines and their metabolites

“…49,148 Whilst random urine samples have also been proposed for diagnosing phaeochromocytoma in adults, 149,150 the measurement of free catecholamines and total metadrenalines has generally been undertaken using 24-h urine samples since this represents an integrated index of catecholamine excretion over the extended collection period. However, the problems associated with completeness of 24-h urine collections has led to proposals for alternative collection strategies involving fractional timed urine collections or volume correction by expressing results as ratios to creatinine.…”

High penetrance of pheochromocytoma in multiple endocrine neoplasia 2 caused by germ line RET codon 634 mutation in Japanese patients

“…The screening examinations depended on the institutions where the patients were assessed, but determination of the absence of PHEO was based on measurements of urinary metanephrine and normetanephrine per mg creatinine levels as a minimum (13). To calculate the penetrance of PHEO in MEN2, the index cases for each family were excluded from the calculation.…”

Different diagnostic cut-off values of urinary fractionated metanephrines according to sex for the diagnosis of pheochromocytoma in Korean subjects

“…In addition, Perry et al reported metanephrine and normetanephrine diagnostic cut-off values for pheochromocytoma of 302 µg/d and 733 µg/d, respectively, as measured by tandem mass spectrometry [17]. However, there are limited data to suggest optimal cut-off values in Asian patients, and whether different cut-off values are necessary according to sex has not been evaluated [18]. Here, we aimed to establish cut-off values for urinary fractionated metanephrines for the diagnosis of pheochromocytoma in Korean patients and to determine cut-off values according to sex.…”