neuropeptide-y and Paraganglioma

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.

Topics: Adrenal Gland Neoplasms; Healthy Volunteers; Humans; Metanephrine; Neuropeptide Y; Paraganglioma; Pheochromocytoma; Protein Precursors; Tandem Mass Spectrometry

Specific assays for measurements of circulating chromogranin (Cg) A, CgB, CgC and pancreastatin (Ps) have recently been developed. The aim of the present study was to investigate the usefulness of these markers in diagnosing and following the effects of treatment of patients with phaeochromocytoma, and to compare the results with those concerning other biochemical markers. CgA was elevated in 19/21 (90%), CgB in 17/21 (81%), Ps in 9/21 (43%) and neuropeptide Y in 9/21 (43%) of the patients. Urinary noradrenaline was increased in 19/21 (90%) and urinary adrenaline in 17/19 (89%) of the patients. All patients had increased levels of either urinary catecholamines or plasma chromogranins. In one patient levels of CgA, CgB and Ps were measured at frequent intervals before, during and after surgery. The CgA level fell to normal shortly after the tumour was removed, whereas the CgB level decreased towards normal over the course of several days. Significant correlation was observed between the contents of CgA and CgB in the tumour tissue and the plasma levels of CgA and CgB respectively. We conclude that CgA and CgB are sensitive circulating markers for phaeochromocytoma and that measurements of both urinary catecholamines and plasma chromogranins improve the diagnostic sensitivity. Furthermore, measurements of CgA may be useful in assessing the radicality of surgery in the early postoperative period.

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Biomarkers, Tumor; Catecholamines; Chromogranin A; Chromogranin B; Chromogranins; Creatinine; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Pancreatic Hormones; Paraganglioma; Pheochromocytoma; Prognosis; Proteins

Twenty-two neuroendocrine tumours of the larynx were investigated using a panel of immunocytochemical markers. Three were small cell carcinomas, eight were large cell neuroendocrine carcinomas and 11 were paragangliomas. Twenty were positive for protein gene product 9.5, 19 for neuron-specific enolase, 15 for chromogranin A, nine for bombesin, eight for substance P, eight for neuropeptide Y, eight for metenkephalin, seven for somatostatin, five for calcitonin, eight for calcitonin gene-related peptide and one for vasoactive intestinal polypeptide. Bombesin immunoreactivity was largely restricted to the small cell carcinomas and large cell neuroendocrine carcinomas and neuropeptide Y, metenkephalin and substance P to the paragangliomas. This comprehensive immunocytochemical analysis of neuroendocrine tumours of the larynx demonstrates that these tumours represent special entities but have similar patterns of immunostaining to those of neuroendocrine tumours in other sites.

Topics: Adult; Aged; Aged, 80 and over; Bombesin; Calcitonin; Carcinoma; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Enkephalin, Methionine; Female; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Paraganglioma; Phosphopyruvate Hydratase; Somatostatin; Substance P