cholecystokinin and Malignant-Carcinoid-Syndrome

A procedure for processing-independent quantitation of procholecystokinin (proCCK) and its products has been applied to plasma. The procedure is based on tryptic cleavage after Lys61 and Arg71 with subsequent monospecific radioimmuno-analysis of fragment 62-71 of human proCCK, which again corresponds to fragment 1-10 of CCK-22. The detection limit of the analysis was 0.2 pmol/l. Plasma was extracted with ethanol. In plasma from 13 healthy volunteers the basal concentration with the above-mentioned radioimmunoassay was 1.1 +/- 0.1 pmol/l (mean +/- S.E.M.) before, and 13.7 +/- 0.6 pmol/l after, incubation with trypsin. Two hours after ingestion of a mixed meal, the plasma concentration was 2.0 +/- 0.1 pmol/l before, and 21.7 +/- 1.2 pmol/l after tryptic cleavage. With a conventional CCK radioimmunoassay specific for the C-terminally amidated and O-sulfated bioactive epitope, the concentration was 1.0 +/- 0.1 pmol/l in the basal state and 4.2 +/- 0.4 pmol/l 2 h after a meal. Tryptic cleavage did not increase the concentrations of amidated, bioactive CCK peptides. In plasma from 37 patients with the carcinoid syndrome, the basal concentration of proCCK and its products was 14.1 (2.8-150.4) pmol/l (median (range)), compared with 0.3 (0-18.8) pmol/l for carboxyamidated CCK. Only two patients had significantly elevated CCK concentrations. We conclude that processing-independent analysis is useful for quantitation of proCCK and its products in plasma, since it quantitates CCK cell secretion more accurately than conventional CCK assays.

Topics: Adult; Cholecystokinin; Chromatography, Gel; Duodenum; Female; Humans; Hydrolysis; Intestinal Mucosa; Intestinal Neoplasms; Male; Malignant Carcinoid Syndrome; Middle Aged; Peptides; Plasma; Protein Precursors; Protein Processing, Post-Translational; Radioimmunoassay; Trypsin

A diffuse peptide microcarcinoidosis was observed both in a 56-year-old man with chronic atrophic gastritis and in a 33-year-old female with chronic atrophic gastritis and pernicious anaemia. Besides hyperplasia of endocrine cells at the base of gastric fundus and corpus mucosa with infiltration of the mucosal muscular layer multiple macro- and micropolyp carcinoids were present. In both cases serotonin was demonstrated immunohistochemically in the intestinal metaplastic mucosal changes, in the microcarcinoidosis foci and in the carcinoids. However, no appropriate clinical symptomatology was observed. The diagnosis can already be made by biopsy which must be deep enough and include gastric mucosa containing the mucosal muscular layer. Should gastric carcinoid be established histologically the other macroscopically normal mucosa must also be biopsied for exclusion of diffuse microcarcinoidosis as intermediate form of a multiple carcinoid. In such a case treatment consists of total gastrectomy.

Topics: Adult; Anemia, Pernicious; Cholecystokinin; Female; Gastrectomy; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Humans; Hyperplasia; Male; Malignant Carcinoid Syndrome; Middle Aged; Serotonin; Somatostatin; Stomach Neoplasms

Topics: Achlorhydria; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Cholecystokinin; Diarrhea; Endocrine System Diseases; Humans; Hypokalemia; Malignant Carcinoid Syndrome; Neoplasms; Pancreatic Diseases; Paraganglioma; Paraneoplastic Endocrine Syndromes; Peptides; Prostaglandins E; Somatostatin; Syndrome; Thyroid Neoplasms; Vasoactive Intestinal Peptide