pancreastatin and Pheochromocytoma

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

We have reported previously the localization of the 49 amino acid peptide pancreastatin to all identifiable endocrine cells of porcine gut, pancreas and adrenal, thyroid and pituitary glands. In this study, we have investigated the occurrence of pancreastatin in a series of human neuroendocrine tumours using an antibody to whole synthetic porcine pancreastatin. The most consistent immunostaining for pancreastatin was found in carcinoid tumours of ileum (four out of six), rectum (four out of six), ovary (two out of two) and lung (nine out of 10). Radioimmunoassay of tumour extracts showed that the concentrations of pancreastatin in ileal carcinoids were very high (mean 71.6, range 31.0-184.0 pmol g-1). The high rate of positivity in lung carcinoids contrasted sharply with the results of 10 pulmonary small cell carcinomas which displayed no immunoreactivity and contained minimal concentrations of pancreastatin (mean 2.0, range 0-6.0 pmol g-1). Extra-adrenal paragangliomas also contained pancreastatin (seven out of 10), but although radioimmunoassay detected peptide in phaeochromocytomas (mean 29.8, range 8.0-69.0 pmol g-1), immunocytochemistry did not. Porcine pancreastatin shows structural homology with bovine chromogranin A, an observation which has led to suggestions that chromogranin is a precursor for the peptide. More recently, a sequence homologous to porcine pancreastatin has been identified in the human chromogranin A molecule. In this study, immunostaining with an antiserum to human chromogranin gave positive results in most cases of each tumour type except the small cell carcinomas. The lack of consistent relationships between chromogranin and pancreastatin immunoreactivities may reflect the fact that the antiserum to pancreastatin was raised against the porcine peptide. When antibodies to human pancreastatin become available, the peptide may prove to be a more consistent marker for neuroendocrine tumours.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Carcinoid Tumor; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Cross Reactions; Humans; Immunohistochemistry; Lung Neoplasms; Neoplasms; Pancreatic Hormones; Pancreatic Neoplasms; Pheochromocytoma; Radioimmunoassay