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Plasma methoxytyramine: clinical utility with metanephrines for diagnosis of pheochromocytoma and paraganglioma


Rao, Dipti; Peitzsch, Mirko; Prejbisz, Aleksander; Hanus, Katarzyna; Fassnacht, Martin; Beuschlein, Felix; Brugger, Christina; Fliedner, Stephanie; Langton, Katharina; Pamporaki, Christina; Gudziol, Volker; Stell, Anthony; Januszewicz, Andrzej; Timmers, Henri J L M; Lenders, Jacques W M; Eisenhofer, Graeme (2017). Plasma methoxytyramine: clinical utility with metanephrines for diagnosis of pheochromocytoma and paraganglioma. European Journal of Endocrinology, 177(2):103-113.

Abstract

CONTEXT: Measurements of plasma methoxytyramine, the O-methylated dopamine metabolite, are useful for detecting rare dopamine-producing pheochromocytomas and paragangliomas (PPGLs) and head and neck paragangliomas (HNPGLs), but utility for screening beyond that achieved using standard measurements of normetanephrine and metanephrine is unclear.
OBJECTIVE: Evaluation of the additional utility of methoxytyramine compared to plasma normetanephrine and metanephrine for diagnosis of PPGLs and HNPGLs.
DESIGN: Comparative prospective study.
METHODS: Comparison of mass spectrometric-based measurements of plasma methoxytyramine, normetanephrine and metanephrine in 1963 patients tested for PPGLs at six tertiary medical centers according to reference intervals verified in 423 normotensive and hypertensive volunteers.
RESULTS: Of the screened patients, 213 had PPGLs and 38 HNPGLs. Using an upper cut-off of 0.10 nmol/L for methoxytyramine, 0.45 nmol/L for metanephrine and age-specific upper cut-offs for normetanephrine, diagnostic sensitivity with the addition of methoxytyramine increased from 97.2% to 98.6% for patients with PPGLs and from 22.1% to 50.0% for patients with HNPGLs, with a small decrease in specificity from 95.9% to 95.1%. Addition of methoxytyramine did not significantly alter areas under receiver operating characteristic curves for patients with PPGLs (0.984 vs 0.991), but did increase (P < 0.05) areas for patients with HNPGLs (0.627 vs 0.801). Addition of methoxytyramine also increased the proportion of patients with PPGLs who showed highly positive predictive elevations of multiple metabolites (70.9% vs 49.3%).
CONCLUSIONS: While the benefit of additional measurements of plasma methoxytyramine for the detection of PPGLs is modest, the measurements do assist with positive confirmation of disease and are useful for the detection of HNPGLs.

Abstract

CONTEXT: Measurements of plasma methoxytyramine, the O-methylated dopamine metabolite, are useful for detecting rare dopamine-producing pheochromocytomas and paragangliomas (PPGLs) and head and neck paragangliomas (HNPGLs), but utility for screening beyond that achieved using standard measurements of normetanephrine and metanephrine is unclear.
OBJECTIVE: Evaluation of the additional utility of methoxytyramine compared to plasma normetanephrine and metanephrine for diagnosis of PPGLs and HNPGLs.
DESIGN: Comparative prospective study.
METHODS: Comparison of mass spectrometric-based measurements of plasma methoxytyramine, normetanephrine and metanephrine in 1963 patients tested for PPGLs at six tertiary medical centers according to reference intervals verified in 423 normotensive and hypertensive volunteers.
RESULTS: Of the screened patients, 213 had PPGLs and 38 HNPGLs. Using an upper cut-off of 0.10 nmol/L for methoxytyramine, 0.45 nmol/L for metanephrine and age-specific upper cut-offs for normetanephrine, diagnostic sensitivity with the addition of methoxytyramine increased from 97.2% to 98.6% for patients with PPGLs and from 22.1% to 50.0% for patients with HNPGLs, with a small decrease in specificity from 95.9% to 95.1%. Addition of methoxytyramine did not significantly alter areas under receiver operating characteristic curves for patients with PPGLs (0.984 vs 0.991), but did increase (P < 0.05) areas for patients with HNPGLs (0.627 vs 0.801). Addition of methoxytyramine also increased the proportion of patients with PPGLs who showed highly positive predictive elevations of multiple metabolites (70.9% vs 49.3%).
CONCLUSIONS: While the benefit of additional measurements of plasma methoxytyramine for the detection of PPGLs is modest, the measurements do assist with positive confirmation of disease and are useful for the detection of HNPGLs.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:August 2017
Deposited On:22 Aug 2017 15:45
Last Modified:19 Feb 2018 08:26
Publisher:BioScientifica Ltd.
ISSN:0804-4643
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1530/EJE-17-0077
PubMed ID:28476870

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