Kantonsspital St.Gallen

Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma

Philippe J Eugster, Jonathan Maurer, Céline Vocat, Karim Abid, Maurice Matter, Grégoire Wuerzner, Roman Trepp, Stefan Fischli, Christoph Henzen, Walter Kolb, Stefan Bilz, Sarah Sigrist, Felix Beuschlein, Svenja Nölting, Astrid Reul, Ina Schütze, Scott A Hubers, Nancy J Brown & Eric Grouzmann

abstract Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.
citation Eugster P J, Maurer J, Vocat C, Abid K, Matter M, Wuerzner G, Trepp R, Fischli S, Henzen C, Kolb W, Bilz S, Sigrist S, Beuschlein F, Nölting S, Reul A, Schütze I, Hubers S A, Brown N J, Grouzmann E. Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma. Clin Chim Acta 2022; 534:146-155.
type journal paper/review (English)
date of publishing 26-07-2022
journal title Clin Chim Acta (534)
ISSN electronic 1873-3492
pages 146-155
PubMed 35905838
DOI 10.1016/j.cca.2022.07.018