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ProSAAS peptide of the granin protein family in biochemical diagnostics of pheochromocytoma
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
open access
Abstract
Introduction: Pheochromocytoma is a hormonally active tumour originating from neuroendocrine cells of the adrenal medulla. Chromogranin A (CgA) and peptide proSAAS belong to the family of granins and are present in neuroendocrine cells of adrenal medulla, from where they are released to circulation, along with catecholamines. The aim of this study was to assess the usability of proSAAS peptide assay in patients with adrenal pheochromocytoma.
Material and methods: 23 patients (13 females and 10 males) with adrenal pheochromocytoma (benign in 18 patients and malignant in 5) confirmed by histopathology examination, and 35 blood donors as a control group. Plasma free metanephrines, CgA, and proSAAS peptide levels were measured in all participants.
Results: CgA and proSAAS levels in the group of pheochromocytoma patients vs. the control were: 209 ng/mL and 0.8 ng/mL vs. 59 ng/mL and 0.3 ng/mL (p < 0.001), respectively. The following sensitivity and specificity indexes were obtained from ROC curves for CgA: 83% and 92%, respectively, and for the proSAAS peptide: 39% and 88%, respectively. The combination of 2 parameters: normetanephrine and proSAAS (96% and 100%) had a high diagnostic value, and the value of all determined parameters together (metanephrine, normetanephrine, CgA, and proSAAS) was 100%.
Conclusion: A single determination of the proSAAS peptide level is associated with a rather low diagnostic value. But collective determination of CgA and proSAAS may be an additional, valuable tool in biochemical diagnostics of pheochromocytoma.
Abstract
Introduction: Pheochromocytoma is a hormonally active tumour originating from neuroendocrine cells of the adrenal medulla. Chromogranin A (CgA) and peptide proSAAS belong to the family of granins and are present in neuroendocrine cells of adrenal medulla, from where they are released to circulation, along with catecholamines. The aim of this study was to assess the usability of proSAAS peptide assay in patients with adrenal pheochromocytoma.
Material and methods: 23 patients (13 females and 10 males) with adrenal pheochromocytoma (benign in 18 patients and malignant in 5) confirmed by histopathology examination, and 35 blood donors as a control group. Plasma free metanephrines, CgA, and proSAAS peptide levels were measured in all participants.
Results: CgA and proSAAS levels in the group of pheochromocytoma patients vs. the control were: 209 ng/mL and 0.8 ng/mL vs. 59 ng/mL and 0.3 ng/mL (p < 0.001), respectively. The following sensitivity and specificity indexes were obtained from ROC curves for CgA: 83% and 92%, respectively, and for the proSAAS peptide: 39% and 88%, respectively. The combination of 2 parameters: normetanephrine and proSAAS (96% and 100%) had a high diagnostic value, and the value of all determined parameters together (metanephrine, normetanephrine, CgA, and proSAAS) was 100%.
Conclusion: A single determination of the proSAAS peptide level is associated with a rather low diagnostic value. But collective determination of CgA and proSAAS may be an additional, valuable tool in biochemical diagnostics of pheochromocytoma.
Keywords
pheochromocytoma; proSAAS; chromogranin A; CgA; adrenal tumour
Title
ProSAAS peptide of the granin protein family in biochemical diagnostics of pheochromocytoma
Journal
Issue
Article type
Original paper
Pages
330-335
Published online
2022-04-05
Page views
5334
Article views/downloads
1010
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2022;73(2):330-335.
Keywords
pheochromocytoma
proSAAS
chromogranin A
CgA
adrenal tumour
Authors
Piotr Glinicki
Magdalena Ostrowska
Lucyna Papierska
Wojciech Zgliczyński
- Granberg D, Juhlin CC, Falhammar H. Metastatic Pheochromocytomas and Abdominal Paragangliomas. J Clin Endocrinol Metab. 2021; 106(5): e1937–e1952.
- Lenders JWM, Duh QY, Eisenhofer G, et al. Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(6): 1915–1942.
- Jian M, Huang H, Li K, et al. A 3-min UPLC-MS/MS method for the simultaneous determination of plasma catecholamines and their metabolites: Method verification and diagnostic efficiency. Clin Biochem. 2021; 87: 67–73.
- Helle KB, Metz-Boutigue MH, Cerra MC, et al. Chromogranins: from discovery to current times. Pflugers Arch. 2018; 470(1): 143–154.
- Lee SN, Prodhomme E, Lindberg I. Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS. J Endocrinol. 2004; 182(2): 353–364.
- Eisenhofer G, Deutschbein T, Constantinescu G, et al. Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma. Clin Chem Lab Med. 2020; 59(2): 353–363.
- Raber W, Kotal H, Marculescu R, et al. Measurements of Plasma-Free Metanephrines by Immunoassay Versus Urinary Metanephrines and Catecholamines by Liquid Chromatography with Amperometric Detection for the Diagnosis of Pheochromocytoma/Paraganglioma. J Clin Med. 2020; 9(10).
- Pussard E, Chaouch A, Said T. Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine-producing tumors. Clin Chem Lab Med. 2014; 52(3): 437–444.
- Guillemot J, Thouënnon E, Guérin M, et al. Granins and their derived peptides in normal and tumoral chromaffin tissue: Implications for the diagnosis and prognosis of pheochromocytoma. Regul Pept. 2010; 165(1): 21–29.
- Gupta N, Bark SJ, Lu WD, et al. Mass spectrometry-based neuropeptidomics of secretory vesicles from human adrenal medullary pheochromocytoma reveals novel peptide products of prohormone processing. J Proteome Res. 2010; 9(10): 5065–5075.
- Bartolomucci A, Possenti R, Mahata SK, et al. The extended granin family: structure, function, and biomedical implications. Endocr Rev. 2011; 32(6): 755–797.
- Glinicki P, Jeske W, Kapuścińska R, et al. Comparison of chromogranin A (CgA) levels in serum and plasma (EDTA2K) and the respective reference ranges in healthy males. Endokrynol Pol. 2015; 66(1): 53–56.
- Glinicki P, Jeske W, Bednarek-Papierska L, et al. Chromogranin A (CgA) in adrenal tumours. Endokrynol Pol. 2013; 64(5): 358–362.
- Plouin PF, Amar L, Dekkers OM, et al. Guideline Working Group, French group of Endocrine and Adrenal tumors (Groupe des Tumeurs Endocrines-REseau NAtional des Tumeurs ENdocrines and COrtico-MEdullo Tumeurs Endocrines networks). Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab. 2005; 90(4): 2110–2116.
- Parisien-La Salle S, Provençal M, Bourdeau I. Chromogranin A in a Cohort of Pheochromocytomas and Paragangliomas: Usefulness at Diagnosis and as an Early Biomarker of Recurrence. Endocr Pract. 2021; 27(4): 318–325.
- Grossrubatscher E, Dalino P, Vignati F, et al. The role of chromogranin A in the management of patients with phaeochromocytoma. Clin Endocrinol (Oxf). 2006; 65(3): 287–293.
- Bílek R, Zelinka T, Vlček P, et al. Radioimmunoassay of chromogranin A and free metanephrines in diagnosis of pheochromocytoma. Physiol Res. 2017; 66(Suppl 3): S397–S408.
- Feng Y, Reznik SE, Fricker LD. Distribution of proSAAS-derived peptides in rat neuroendocrine tissues. Neuroscience. 2001; 105(2): 469–478.
- Hoshino A, Helwig M, Rezaei S, et al. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease. J Neurochem. 2014; 128(3): 419–430.
- Wardman JH, Berezniuk I, Di S, et al. ProSAAS-derived peptides are colocalized with neuropeptide Y and function as neuropeptides in the regulation of food intake. PLoS One. 2011; 6(12): e28152.
- Morgan DJ, Wei S, Gomes I, et al. The propeptide precursor proSAAS is involved in fetal neuropeptide processing and body weight regulation. J Neurochem. 2010; 113(5): 1275–1284.
- Hatcher NG, Atkins N, Annangudi SP, et al. Mass spectrometry-based discovery of circadian peptides. Proc Natl Acad Sci U S A. 2008; 105(34): 12527–12532.