gastrins and Adenoma--Islet-Cell

Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

Topics: Adenoma, Islet Cell; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Islet Cell; Catheter Ablation; Chemoembolization, Therapeutic; Evidence-Based Medicine; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Quality of Life; Somatostatin; Survival Analysis; Treatment Outcome

The authors review clinical applications of gut-derived peptides as diagnostic and therapeutic agents.. An increasing number of gut peptides have been evaluated for clinical use. Earlier uses as diagnostic agents have been complemented more recently by increasing application of gut peptides as therapeutic agents.. The authors conducted a literature review.. Current experience with clinical use of gut peptides is described. Initial clinical applications focused on using secretomotor effects of gut peptides in diagnostic tests, many of which have now fallen into disuse. More recently, attention has been directed toward harnessing these secretomotor effects for therapeutic use in a variety of disorders, and also using the trophic effects of gut peptides to modulate gut mucosal growth in benign and malignant disease. Gut peptides have been evaluated in a variety of other clinical situations including use as adjuncts to imaging techniques, and modification of behaviors such as feeding and panic disorder.. Gut peptides have been used successfully in an increasing variety of clinical conditions. Further refinements in analogue and antagonist design are likely to lead to even more selective agents that may have important clinical applications. Further studies are needed to identity and evaluate these new agents.

Topics: Adenoma, Islet Cell; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Motilin; Pancreatic Polypeptide; Secretin; Somatostatin

Topics: Achlorhydria; Acromegaly; Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Calcium; Cushing Syndrome; Diarrhea; Female; Gastric Acid; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Hypoglycemia; Hypokalemia; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Polypeptide; Pancreatitis; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Thyroid Diseases; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Humans; Insulin; Insulin Secretion; Insulinoma; Pancreatectomy; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Cytoplasmic Granules; Gastrins; Glucagon; Humans; Insulin; Multiple Endocrine Neoplasia; Neoplasms, Hormone-Dependent; Pancreatic Neoplasms; Proinsulin; Somatostatin

Gastrointestinal hormones (GI hormones) have received growing interest in endocrinology, gastroenterology and neuroendocrinology. Because of new methodological techniques, they can be measured in plasma and therefore be related to different pathophysiological conditions. In childhood, our present knowledge is as yet limited to the physiological rôle of gastrin at different ages and in some diseases (gastrinoma; Verner-Morrison syndrome) caused by humoral dysfunction. The present review relates the clinical important GI hormones to chemically classified families. The diagnostic value of determining endogenous hormone concentration in plasma and the validity of function tests carried out by administration of exogenous hormones are pointed out. Particular emphasis is given to the trophic action of GI hormones in the development and function of the gastrointestinal tract during childhood. More speculatively, GI hormones are involved in the complex function of the central nervous system, thus making food intake a trophotropic action in a broader sense.

Topics: Adenoma, Islet Cell; Bombesin; Ceruletide; Child; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Motilin; Neurotensin; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Female; Gastrins; Humans; Insulin; Insulin Secretion; Male; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Apudoma; Dehydration; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Parathyroid Neoplasms; Pheochromocytoma; Postgastrectomy Syndromes; Somatostatin; Syndrome; Thyroid Neoplasms; Zollinger-Ellison Syndrome

The pathology and cell biology of endocrine pancreatic tumors are reviewed. It is probable that all these tumors are "functioning" in the sense that they elaborate hormones that cause more or less conspicuous clinical syndromes. Identification of such secretory products is essential for an optimal diagnosis, localization, treatment, and follow-up. Recent data indicate that endocrine pancreatic tumors evolve from progenitor cells of ducts. This histogenetic mechanism may explain the occurrence not only of mixed or multihormonal tumors but also of tumors producing hormones that are absent from the adult human pancreas. In addition to their clinically apparent effects, many endocrine pancreatic tumors affect the surrounding endocrine pancreas in a characteristic way. The mechanisms behind and the potential diagnostic usefulness of these changes are discussed.

Topics: Adenoma, Islet Cell; Adult; Animals; APUD Cells; Child; Gastrins; Glucagon; Humans; Infant, Newborn; Islets of Langerhans; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Somatostatin

Topics: Adenoma, Islet Cell; Cholecystokinin; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Neoplasms; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Precancerous Conditions; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adolescent; Adult; Aged; Carcinoid Tumor; Child; Dehydration; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Hyperplasia; Hypokalemia; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Precancerous Conditions; Serotonin; Somatostatin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Amines; Carboxy-Lyases; Dehydration; Endocrine Glands; Fluorescent Antibody Technique; Gastrins; Glucagon; Humans; Hyperplasia; Intestinal Neoplasms; Intestinal Secretions; Intestines; Male; Multiple Endocrine Neoplasia; Neurosecretory Systems; Pancreas; Paraneoplastic Endocrine Syndromes; Peptides; Zollinger-Ellison Syndrome

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable elect

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Chromaffin System; Digestive System; Duodenal Ulcer; Endocrine System Diseases; Enterochromaffin Cells; Esophagitis, Peptic; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Intestinal Mucosa; Metabolic Diseases; Serotonin; Somatostatin; Stomach Neoplasms; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adenoma, Islet Cell; Animals; Binding Sites; Blood Glucose; Diabetes Mellitus; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Secretory Rate; Somatostatin; Thyrotropin

Topics: Adenoma, Islet Cell; Animals; Diabetes Mellitus; Diarrhea; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; Pancreatic Hormones; Pancreatic Neoplasms; Peptic Ulcer; Somatostatin; Transplantation, Homologous

The Verner-Morrison Syndrome is a clinically defined entity caused by an islet cell tumor of the pancreas. More than 60 cases have been described so long. The syndrome is characterized by diarrhea, hypokalemia and hypochlorhydria. In addition to a diabetic disposition, raised calcium levels and skin alterations may be present. The diagnosis is a clinical one. A pancreatic tumor should be searched for and removed. Morphologically a benign and a maligne islet cell tumor or a diffuse hyperplasia of the islets of Langerhans can be found. Until now identification of the tumor cells has not been possible. There seems no doubt that the tumor cells produce a peptide hormone. Secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide and combinations of hormones are discussed. The results are contradictory. Theories concerning the formal and causal pathogenesis are only incomplete and unproved up to now.

Topics: Achlorhydria; Adenoma, Islet Cell; Adolescent; Adult; Aged; Diarrhea; Female; Gastrins; Glucagon; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Pancreatic Neoplasms; Peptides; Pregnancy; Secretin; Syndrome

Topics: Adenoma, Islet Cell; Diagnosis, Differential; Diarrhea; Gastrins; Germany, West; Glucagon; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Malignant Carcinoid Syndrome; Pancreatic Neoplasms; Syndrome; Zollinger-Ellison Syndrome

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.

Topics: Adenoma, Islet Cell; Adult; Female; Gastrectomy; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Streptozocin; Zollinger-Ellison Syndrome

The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.

Topics: Achlorhydria; Adenoma, Islet Cell; Angiography; Calcium; Diagnosis, Differential; Diarrhea; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperinsulinism; Hyperparathyroidism, Secondary; Neoplasm Metastasis; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Biogenic Amines; Carcinoid Tumor; Decarboxylation; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Histocytochemistry; Intestinal Mucosa; Islets of Langerhans; Pancreatic Neoplasms; Serotonin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Diarrhea; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neurosecretory Systems; Pancreatic Hormones; Paraneoplastic Endocrine Syndromes; Prostaglandins; Serotonin; Syndrome; Vasoactive Intestinal Peptide; Werner Syndrome; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Diabetes Mellitus; Gastrins; Glucagon; Growth Hormone; Humans; Hypoglycemia; Neoplasms; Pancreatic Neoplasms; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely.

Topics: Adenoma, Islet Cell; Age Factors; Celiac Disease; Diagnosis, Differential; Diarrhea; Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Hormones; Pancreatic Neoplasms; Preoperative Care; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Calcium; Endocrine System Diseases; Gastrins; Humans; Insulin; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pheochromocytoma; Pituitary Neoplasms; Radioimmunoassay; Syndrome; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Duodenal Neoplasms; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Peptic Ulcer; Radiography; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cholecystokinin; Dehydration; Diarrhea; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypercalcemia; Hypokalemia; Kidney Diseases; Male; Pancreatic Neoplasms; Protein Precursors; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Amino Acid Sequence; Animals; Catecholamines; Dehydration; Diarrhea; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Intestinal Mucosa; Peptic Ulcer; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastric Acidity Determination; Gastrins; Glucagon; Humans; Islets of Langerhans; Pancreatic Neoplasms; Syndrome; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Angiography; Antacids; Celiac Disease; Diarrhea; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pancreatic Neoplasms; Physical Examination; Radioimmunoassay; Radionuclide Imaging; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Diagnosis, Differential; Gastrins; Glucose Tolerance Test; Humans; Hyperparathyroidism; Insulin; Pancreatic Neoplasms; Parathyroid Neoplasms; Radioimmunoassay; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Female; Gastrectomy; Gastrins; Humans; Male; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Acute Disease; Adenoma, Islet Cell; Cholecystokinin; Chronic Disease; Gastrins; Humans; Methods; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin; Transplantation, Homologous; Zollinger-Ellison Syndrome

Topics: 5-Hydroxytryptophan; Adenoma; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Calcitonin; Catecholamines; Corticosterone; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Kinins; Pancreas; Pancreatic Neoplasms; Peptides; Prostaglandins; Secretin; Thyrotropin; Vasopressins; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Diarrhea; Digestive System; Fasting; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Hypoglycemia; Hypokalemia; Leucine; Pancreatic Neoplasms; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastric Mucosa; Gastrins; Histocytochemistry; Hormones, Ectopic; Humans; Intestinal Mucosa; Microscopy, Electron; Secretory Rate; Zollinger-Ellison Syndrome

Although patients with neuroendocrine tumors typically exhibit an indolent clinical course, the pace of disease accelerates and the prognosis deteriorates once objective progression of disease begins. Thirty-four patients with advanced neuroendocrine tumors were treated with octreotide as antineoplastic therapy. This treatment was begun only after documentation of clear objective progression of disease.. A Phase II trial was performed at a tertiary comprehensive cancer center.. The median survival for this patient population from the start of octreotide therapy has not been reached, with a median follow-up of 29 months (range, 1-47 months). No major objective tumor regressions were seen. Seventeen patients (50%) experienced a computed tomography-documented stabilization of disease that was maintainable for a minimum of 2 months (median, 5 months; range, 0-27 months). Of the 34 patients, 20 patients received octreotide as their first antineoplastic therapy. The median survival for these 20 patients has not been reached, with a median follow-up also of 29 months (range, 12-41 months).. Octreotide may influence the natural history of neuroendocrine tumors. The survival in patients treated with octreotide, as measured from the time of progression of disease, compares favorably with that of historical controls. Proof of a survival advantage for patients treated with octreotide would require a multicenter, randomized trial.

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Female; Gastrins; Humans; Male; Middle Aged; Neoplasm Staging; Octreotide; Pancreatic Neoplasms; Survival Analysis

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by non-beta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion,multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.

Topics: Adenoma, Islet Cell; Diarrhea; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Phenotype; Zollinger-Ellison Syndrome

The major phenotypes of multiple endocrine neoplasia type 1 (MEN 1) consist of three lesions characterized by hyperparathyroidism, pituitary tumors, and endocrine pancreatic tumors. The endocrine pancreatic tumors are a significant cause of disease-related mortality in MEN 1. Although symptomatic pancreatic tumors such as insulinoma and gastrinoma should be resected, the management of asymptomatic pancreatic tumors is not established. In asymptomatic pancreatic tumors, the most important factor is the propensity for malignant transformation of the tumors. Although there are no means to foresee it, the size of the pancreatic tumors might be predictive of malignant development in MEN 1. We report here a patient with MEN 1 who had a large asymptomatic pancreatic tumor. The patient (72-yr-old man) was diagnosed with primary hyperparathyroidism and underwent a total parathyroidectomy. Genetic examination showed a germline mutation of the MEN1 gene (E45G). Abdominal magnetic resonance imaging revealed a large (>6 cm) tumor with a heterogeneous pattern in the tail of the pancreas. No metastases of the tumor were evident. Serum levels of insulin, gastrin, and glucagon were normal, and the patient had no symptoms. Operative resection was performed, and microscopic examination revealed that the tumor was an islet cell tumor stained with multiple hormones. This is a case indicating that asymptomatic pancreatic tumors associated with MEN 1 might be indolent independent of their size.

Topics: Adenoma, Islet Cell; Aged; Angiography; Gastrins; Germ-Line Mutation; Glucagon; Humans; Hyperparathyroidism; Immunohistochemistry; Insulin; Magnetic Resonance Imaging; Male; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Parathyroidectomy; Serotonin; Spleen

A nongastrin acid-stimulating peptide (NGASP) has been found in ulcerogenic pancreatic tumor syndrome without hypergastrinemia. The mechanism of gastric acid hypersecretion by NGASP was investigated in rats.. In vivo, gastric acid secretion and in vitro histamine release from enterochromaffin-like (ECL) cells in responses to tumor extract (TE) and synthetic human gastrin-17 I or pentagastrin (PG) were studied. Whether the 2 secretagogues potentiate each other was determined.. TE dose-dependently stimulated histamine release, which was not blocked by a cholecystokinin (CCK)-B receptor antagonist. When TE was incubated with trypsin, the activity was abolished but was not affected by antibody. However, when rats were pretreated with antigastrin serum or CCK-B receptor antagonist, the acid secretion by TE was virtually abolished. The dose response of acid secretion to TE in the rats receiving PG in a threshold dose was significantly greater than that achieved by TE alone. Similarly, the dose response to PG combined with a threshold dose of TE was significantly greater than that produced by PG alone.. NGASP stimulates histamine release from ECL cells, but the release is not mediated via CCK-B/gastrin receptor. NGASP and gastrin may potentiate each other to produce acid hypersecretion in ulcerogenic pancreatic tumor syndrome.

Topics: Adenoma, Islet Cell; Animals; Enterochromaffin Cells; Gastric Acid; Gastric Mucosa; Gastrins; Histamine Release; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pentagastrin; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Tissue Extracts

Gastrin is expressed in the gastric antrum and in fetal pancreatic islets but not in adult islets. We have now identified the hepatobiliary tract as another, previously unknown, potential site of gastrin gene expression. Two human gastrin simian virus 40 large tumor antigen (SV40 T antigen) fusion genes containing 1.5 kb of 5' flanking sequence and 10.5 kb that included 5.5 kb upstream, 1.5 kb downstream, and the entire transcribed region were used to generate transgenic mice. Analysis of several transgenic lines, derived from both fusion genes, revealed development of transmissible hepatobiliary tract tumors and pancreatic islet cell tumors. Analysis of each of the tumor cells demonstrates expression of SV40 T antigen but no expression of gastrin. Of the two fusion genes, only the 10.5-kb sequence induces hyperplasia of gastrin-producing cells in the antrum. Analysis of these cells demonstrates expression of SV40 T antigen and gastrin, suggesting that the 10.5-kb sequence is sufficient for gastrin cell hyperplasia in the antrum. These data raise the possibility that gastrin is transiently expressed in the hepatobiliary tract.

Topics: Adenoma, Islet Cell; Animals; Antigens, Viral, Tumor; Biliary Tract Neoplasms; Gastric Mucosa; Gastrins; Hyperplasia; Hypoglycemia; Mice; Mice, Nude; Mice, Transgenic; Pyloric Antrum; Recombinant Fusion Proteins; Simian virus 40

We previously established pluripotent transformed rat islet cell lines, MSL-cells, of which certain clones have been used to study processes of islet beta-cell maturation, including the transcriptional activation of the insulin gene induced by in vivo passage. Thus, successive sc transplantation in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (< 0.3% of total body weight), and the observed weight loss parallels that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor necrosis factor (cachectin) was not produced by any of the tumors. Proglucagon was processed as in the fetal islet to products representative of both pancreatic alpha-cell and intestinal L-cell phenotypes, with glucagon and Glp-1 (7-36)amide as the major extractable products. In contrast to the administration of cholecystokinin, neither glucagon, Glp-1 (7-36)amide, nor their combination, affected feeding behavior in fasted mice, suggesting the presence of a hitherto unidentified anorectic substance released from the glucagonoma. We conclude 1) that glucagonomas and insulinomas can be derived from a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported in animals carrying tumor necrosis factor-producing experimental

Topics: Adenoma, Islet Cell; Animals; Anorexia; Base Sequence; Blotting, Northern; Cholecystokinin; Eating; Gastrins; Gene Expression; Glucagon; Hormones; Hypoglycemia; Molecular Sequence Data; Neoplasm Transplantation; Pancreatic Neoplasms; Protein Precursors; Rats; Tumor Cells, Cultured; Weight Loss

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Bombesin; Calcitonin; Carcinoid Tumor; Carcinoma, Small Cell; Chromatography, Gel; Corticotropin-Releasing Hormone; Gastrin-Releasing Peptide; Gastrins; Humans; Hypothalamus; Lung Neoplasms; Neoplasms; Neuroblastoma; Pancreatic Neoplasms; Peptides; Pheochromocytoma; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.

Topics: Adenoma, Islet Cell; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Carcinoma; Cisplatin; Etoposide; Female; Gastrins; Glucagon; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Remission Induction; Survival Rate

In 98 patients with histologically proved pancreatic islet cell carcinoma who were studied between 1950 and 1987, 55 had functioning tumors and 43 had nonfunctioning tumors. Both patient groups were compared in regard to age at presentation, metastases, and survival. Mean age at diagnosis was 51.1 years for the 55 men and 47 years for the 43 women. At diagnosis, 51 of the patients had regional disease and 47 had distant metastases. When matched for age, sex, and extent of disease, survival did not differ significantly in cases of functioning and nonfunctioning tumors. The patients' ages and the extent of disease at presentation were the most significant factors in prognosis and survival.

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Hormones; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Survival Analysis

The insulinoma is the most common pancreas tumour with endocrine activity, with more than 2,000 cases being described in the literature worldwide. The first successful extirpation was performed by Graham in 1928. Clinical appearance is characterized by severe paroxysmal hypoglycaemia together with inadequately increased serum insulin levels. Surgery is indicated in such situations because of limited effectiveness of medicamentous therapy. Surgical approach and long-time results are discussed in this paper, with reference being made to 13 cases of the authors.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Follow-Up Studies; Gastrins; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulinoma; Male; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Reoperation

In two patients with malignant gastrinoma and the Zollinger-Ellison syndrome, we were able to use selective arterial stimulation with secretin as a technique to localize the lesions accurately, allowing resection. The technique of selected arterial secretin stimulation is one of measuring variations in gastrin levels in both the hepatic vein and a peripheral artery at specified times after injection of secretin into a specific artery. When the criteria for localization have been met, one can plot the presence of the gastrinoma within the blood supply of the injected artery and, using angiograms, thus accurately localize the lesion. This method promises to be a valuable additional tumor-localizing procedure, particularly when gastrinomas are extrapancreatic.

Topics: Adenoma, Islet Cell; Angiography; Drug Evaluation; Female; Gastrinoma; Gastrins; Hepatic Veins; Humans; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Secretin; Time Factors; Zollinger-Ellison Syndrome

The occurrence of transthyretin (TTR) in 25 endocrine pancreatic tumors was investigated by immunohistochemical methods using both polyclonal and monoclonal antibodies. All malignant insulinomas were strongly TTR immunoreactive, more so than their benign counterparts, which in some cases were TTR negative. All glucagonomas and nonfunctioning tumors were TTR immunoreactive, whereas gastrinomas and VIPomas were TTR negative. TTR, chromogranin A, and the argyrophil reaction (Grimelius' silver technique) had similar distributions among the cells in many, but not all, tumors. Coexistence of TTR with glucagon, insulin, or pancreatic polypeptide in tumor cells was demonstrated. TTR was also quantitated in preoperative serum samples by electroimmuno assay in some cases. Although one patient with a glucagonoma had a markedly increased serum TTR level, five other patients with endocrine tumors, including two patients with glucagonoma, had TTR levels in serum that were within or below the reference range.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Immunohistochemistry; Immunologic Techniques; Insulin; Pancreatic Neoplasms; Prealbumin; Staining and Labeling; Tissue Distribution

Topics: ACTH Syndrome, Ectopic; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Combined Modality Therapy; Female; Gastrins; Humans; Hydrocortisone; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes

Although part of pancreatic endocrine tumors may be multihormonal by immunohistochemical study, the clinical manifestations are often related to hypersecretion of only one type of peptide hormone. Only a few cases have shown two or more syndromes simultaneously or transition of one type of syndrome to another with the passage of time. The case reported here is an islet cell carcinoma with liver metastases. The clinical manifestations changed from Zollinger-Ellison syndrome to hypoglycemic syndrome with the secretion of gastrin, insulin and serotonin. The immunohistochemical study confirmed multihormonal production. The elevation of growth hormone with acromegaly was also noted in this case. It remains to be seen if the excessive production of growth hormone was due to growth hormone-releasing hormone secreted by the endocrine pancreatic tumor or to the possible presence of a pituitary microadenoma as a component of the multiple endocrine neoplasia type I syndrome.

Topics: Adenoma, Islet Cell; Gastrins; Growth Hormone; Hormones; Humans; Male; Middle Aged; Pancreatic Neoplasms

Ten patients with metastatic pancreatic endocrine tumours were treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13-54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour-related hormones were reduced. Worsening of symptoms and rising levels of tumour-related hormone concentrations occurred a median of 5 months (range 1-6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6-16 months). However, after a median of 13 months (range 5-34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Liver Neoplasms; Octreotide; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide

Topics: Adenoma; Adenoma, Islet Cell; Adrenal Cortex; Female; Gastrins; Glucagon-Like Peptides; Humans; Hydrocortisone; Hyperplasia; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Peptides; Thyroid Gland; Thyroid Hormones

As part of a study to manage islet cell tumors in patients with multiple endocrine neoplasia (MEN), patients with MEN I and Zollinger-Ellison syndrome (ZES) underwent surgery if a pancreatic islet cell tumor was identified on imaging studies. Patients with MEN I and either insulinoma or vasoactive intestinal polypeptide tumor (VIPoma) underwent surgery whether or not a tumor was identified. Each patient underwent preoperative portal venous sampling (PVS). Nine patients with MEN I and one with MEN II underwent surgery; seven had ZES, one had insulinoma, one had VIPoma, and one had both insulinoma and ZES. Eight of the nine patients with MEN I had an identifiable hormone gradient on PVS. Islet cell tumors were removed from the pancreas of each patient; two patients also had duodenal wall tumors, and three patients had malignant islet cell tumors. No patient with ZES and MEN I was cured of ZES despite the fact that islet cell tumor was removed from the region of the gastrin gradient in five of six patients. The single patient with MEN II and ZES and the three additional patients with MEN I and either insulinoma or VIPoma were cured by islet cell tumor resection. The results indicate that islet cell tumors in patients with MEN I can be both extrapancreatic and malignant. In patients with MEN I and ZES, ZES cannot be cured by tumor resection, and PVS cannot be used to select patients for curative surgery. It appears that gastrinoma in patients with MEN II, as well as either insulinoma or VIPoma in patients with MEN I, can be cured by islet cell tumor resection.

Topics: Adenoma, Islet Cell; Adult; Biomarkers, Tumor; Fasting; Female; Follow-Up Studies; Gastrins; Humans; Insulin; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prospective Studies

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Topics: Adenoma, Islet Cell; Adult; Aged; Gastrins; Gastrointestinal Hemorrhage; Glucagon; Glucagonoma; Hormones; Humans; Insulinoma; Middle Aged; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

Signs and symptoms of Cushing's syndrome developed rapidly after total gastrectomy in a 37-yr-old man with a metastatic gastrin-secreting islet cell carcinoma. Argyrophilic tumor cells in a lymph node removed during operation immunostained for gastrin and ACTH. Treatment for more than 6 months with the somatostatin analog SMS 201-995 (300 micrograms/day) greatly reduced serum gastrin levels and normalized plasma ACTH and cortisol levels and urinary cortisol excretion, and the signs and symptoms of Cushing's syndrome disappeared. The size of the primary tumor in the head of the pancreas, which had grown rapidly before SMS 201-995 therapy, stabilized after 6 months of treatment with the analog. We conclude that SMS 201-995 can reduce ACTH as well as gastrin secretion from islet cell carcinomas as well as control tumor growth.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Gastrins; Hormones, Ectopic; Humans; Hydrocortisone; Male; Neoplasm Metastasis; Octreotide; Pancreatic Neoplasms

Acute effects of somatostatin analog (SMS 201-995) on pancreatic hormones were studied in two patients with malignant islet-cell carcinoma. Before and after subcutaneous injection of somatostatin with a doses of 50 micrograms, blood glucose (BG), serum growth hormone (hGH), C-peptide immunoreactivity (CPR), plasma immunoreactive glucagon (IRG) and gastrin were assayed, and changes in elution patterns of IRG and gastrin were also analyzed on Bio-Gel P-30 column chromatography. In Patient 1 with glucagonoma syndrome and hypergastrinemia, a prompt and remarkable decrease in plasma IRG and gastrin was observed after the injection of SMS 201-995 in association with a decrease in blood glucose, and then IRG and gastrin increased gradually. The suppressive effect continued for at least 6 hours. On gel filtration of the plasma obtained before the injection of the analog, three major peaks, greater than 20000, 9000 and 3500 molecular-weight (mol wt) fractions, were seen in IRG fraction. The decrease in plasma IRG observed at 1 hour after the injection was mainly due to a marked decrease in the 3500 molecular weight fraction. In addition, a slight decrease in the 9000 mol wt fraction was seen. At 4 hours after the injection, the 3500 mol wt peak returned to the previous level, while the 9000 mol wt peak decreased further. On the other hand, the gastrin elution pattern of plasma obtained before the injection revealed three major gastrin peaks, greater than 20000, 7000 and 5000 mol wt fraction. The changes in the gastrin elution pattern after the injection were similar to those of the IRG elution pattern. In Patient 2 with Zollinger-Ellison's syndrome, the plasma gastrin level decreased gradually for 5 hours after the injection. On gel filtration of the plasma obtained before the injection, two major gastrin peaks, 7000 and 5000 mol wt fraction, of which the large-molecular fraction was more prominent than the small-molecular fraction, were observed. After the injection, a marked decrease in the small-molecular fraction and a gradual decrease in the large-molecular fraction were observed for 4 hours, accompanied by a decrease in plasma gastrin. At 7 hours after the injection, the smaller fraction was augmented again. The serum CPR and hGH was slightly suppressed after the injection in both patients. The adverse effects of slight nausea and vomiting were noticed only in Patient 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adenoma, Islet Cell; Adult; Blood Glucose; C-Peptide; Depression, Chemical; Female; Gastrins; Glucagon; Growth Hormone; Humans; Middle Aged; Octreotide; Pancreatic Hormones; Pancreatic Neoplasms

The symptoms resulting from the hyperinsulinemia of severe refractory metastatic insulinoma were palliated using self-administered divided doses of a long-acting minisomatostatin analog, octreotide. The substance was well tolerated and the attributable side effects were minimal (primarily gastrointestinal complaints). There were significant improvements in peripheral edema, ascites, and serum electrolytes throughout therapy. Serum insulin and glucagon levels were largely unchanged. Computed tomography scans performed during therapy showed stabilization of pancreatic and hepatic disease. Severe, recurrent hypoglycemic episodes due to hyperinsulinemia were reduced both in number and severity for almost a three-month period. This allowed the elimination or reduction of other chronic, supportive medications and improved quality of life.

Topics: Adenoma, Islet Cell; Antineoplastic Agents; Drug Resistance; Female; Gastrins; Glucagon; Humans; Insulin; Insulinoma; Middle Aged; Neoplasm Metastasis; Octreotide; Pancreatic Neoplasms; Somatostatin

A case of multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I (MEN I) is reported. The patient was a 41-year-old woman who had a past history of thyroid cancer (papillary carcinoma) and hyperparathyroidism due to parathyroid adenoma. Later, a nonfunctional pituitary tumor and five nonfunctional pancreatic tumors were found simultaneously and the patient was finally diagnosed as having MEN I. Following surgical enucleation, the pancreatic tumors were histopathologically diagnosed as benign islet cell tumors. One of them (tumor 3) exhibited a solid nodular pattern while the others showed gyriform patterns. They were divided histochemically and immunohistochemically into three types: two (tumors 1 and 2) produced a single hormone (glucagon), one (tumor 3) produced five (insulin, glucagon, somatostatin, gastrin and pancreatic polypeptide) and the remaining two (tumors 4 and 5) produced two (glucagon and pancreatic polypeptide). Electron microscopically, three types of endosecretory granules were found in the tumor cells of tumor 3 but only one type was found in tumor 4. However, in the tumor 4 extract, glucagon, pancreatic polypeptide, C-peptide, somatostatin, vasoactive intestinal peptide and growth hormone releasing factor were detected by radioimmunoassay. These findings suggest that these pancreatic tumors were both multicellular and multihormonal.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Gastrins; Glucagon; Growth Hormone-Releasing Hormone; Humans; Immunohistochemistry; Insulin; Microscopy, Electron; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Somatostatin; Vasoactive Intestinal Peptide

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.

Topics: Adenoma, Islet Cell; Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; Drug Evaluation; Etoposide; Female; Gastrins; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Thyroid Neoplasms

A tissue specimen taken from the pancreatic tumor of a patient suffering from Zollinger-Ellison syndrome associated with a concurrent Cushing's syndrome was investigated both morphologically and immunohistochemically. Histologically, the tumor cells were found to be arranged in a cord or ribbon pattern. An immunohistochemical study revealed that the tumor nodule contained both gastrin and ACTH. Further, double stainings of the same section disclosed that the same tumor nodule possessed both hormones simultaneously, thus confirming the concurrent presence of Zollinger-Ellison syndrome and Cushing's syndrome. An electron micrograph of the tumor cell showed the presence of numerous endocrine-type granules in the cytoplasm. These findings substantiate the concurrent presence of the two characteristic clinical syndromes.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Gastrins; Humans; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Three antisera to the C-terminally extended form of gastrin or the C-terminal flanking peptide of progastrin were used in an attempt to investigate the post-translational processing of progastrin at the cellular level by light and electron microscopical immunocytochemistry. In the normal human gastric antrum, the G-cell secretory granules were found to contain both gastrin and the C-terminal progastrin determinants (progastrin 87-93, 87-95 and 93-101). Immunostaining of serial sections at the light microscopical level revealed that duodenal gastrin-containing cells also express the C-terminal progastrin determinants, as well as gastrin-34. In foetal tissue, cells containing C-terminal gastrin and the C-flanking peptide of progastrin were first seen at 8 weeks of gestation, in the duodenum. They were not found in the stomach until the 11th week. In hyperplastic G-cells and in gastrin-producing tumour cells, the level of C-terminal peptide immunoreactivity was variable and often lower than that seen in normal antrum and only minimal immunoreactivity could be detected using electron immunocytochemistry. This was interpreted as representing altered post-translational processing of progastrin in modified G-cells.

Topics: Adenoma, Islet Cell; Duodenum; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Immune Sera; Immunohistochemistry; Peptide Fragments; Protein Precursors; Pyloric Antrum; Stomach

Immunocytochemical studies of the distribution of glucagon, gastrin, insulin, and somatostatin in normal canine pancreatic islets and 20 canine islet cell tumors were done using the peroxidase-anti-peroxidase (PAP) technique. In the normal adult canine pancreas, islets typically consisted of clusters of 20-30 cells, but smaller foci and even individual cells were identified. Alpha cells (glucagon) were often peripherally located, beta cells (insulin) were centrally located and most numerous, and delta cells (somatostatin) were the least numerous and randomly located. Both juvenile and adult canine pancreases did not stain for gastrin. Of the 20 tumors examined, 18 had positive immunoreactivity for insulin, nine for glucagon, 14 for somatostatin, and one for gastrin. Two tumors were uninterpretable due to autolysis. Three tumors were pure insulinomas, but no pure somatostatinomas, glucagonomas, or gastrinomas were identified. Most tumors and metastases had mixed positive immunoreactivity; one neoplastic cell type predominated with lesser numbers of other cell types. Metastatic sites (liver and lymph node) stained for insulin and somatostatin, only. Foci of non-neoplastic islet cell tissue (nesidioblastosis), often located at the pancreatic-mesenteric junction, stained strongly positive for insulin, glucagon, and somatostatin but not for gastrin. The tumor staining pattern did not consistently correlate with tumor function, as determined by blood glucose and serum insulin assays. The PAP technique works well on paraffin-embedded, formalin-fixed tissue using rabbit or guinea pig antisera as the primary antibody. Staining occurred on sections of paraffin blocks stored for up to 7 years.

Topics: Adenoma, Islet Cell; Animals; Dog Diseases; Dogs; Female; Gastrins; Glucagon; Immunoenzyme Techniques; Insulin; Islets of Langerhans; Male; Pancreatic Neoplasms; Retrospective Studies; Somatostatin

A patient with metastatic islet cell carcinoma demonstrated multiple clinical syndromes simultaneously with secretion of ACTH, gastrin, glucagon, and serotonin. Hepatic arterial embolization resulted in an initial decrease in all secretory products, which was sustained for glucagon and serotonin. Recrudescence of the Cushings and Zollinger-Ellison syndrome was managed by surgical extirpation of the primary tumor and regional metastases as well as bilateral adrenalectomy. Electron microscopy and immunocytochemistry of the primary tumor and the metastatic lesions revealed the presence of multiple types of granules within single cells and, different patterns of secretory profiles in different tumor sites.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Gastrins; Glucagon; Humans; Liver Neoplasms; Microscopy, Electron; Neoplasm Metastasis; Pancreatic Neoplasms; Tomography, X-Ray Computed

Between 1971 and 1983, 31 males and 13 females were found to have peptic ulceration associated with hypergastrinaemia. An antral G-cell lesion was present in 11 (25 per cent) and a gastrinoma in 14 (32 per cent). There were 11 patients with multiple endocrine adenomatosis (MEA) (25 per cent) and 4 (9 per cent) with primary hyperparathyroidism. Four patients (9 per cent) were unclassified. Length of history and level of gastrin did not differentiate between the groups and an average of 2.5 operations was performed per patient, while the overall mortality was 27.3 per cent. The patients with G-cell lesions were significantly younger than all the other groups (P less than 0.01). Partial gastrectomy adequately treated G-cell hyperplasia. Total gastrectomy was required to treat pancreatic gastrinomata but additional pancreatic resection did not improve the outcome. In MEA, parathyroidectomy did not influence the treatment of a gastrinoma. This is the first recorded experience of surgery for hypergastrinaemia in the United Kingdom and the outcome of such a retrospective study may be a guide to the future management of these conditions.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatectomy; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Female; Gastrins; Humans; Insulinoma; Male; Octreotide; Pancreatic Neoplasms; Somatostatin; Vipoma; Zollinger-Ellison Syndrome

Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger-Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Octreotide; Pancreatic Neoplasms; Somatostatin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Insulinoma; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

A 30-year-old man presenting with watery diarrhea, hypokalemia, and hypochlorhydria (Verner-Morrison syndrome, WDHH syndrome) had raised plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), calcitonin, and gastrin, as well as high urinary excretion of vanillylmandelic acid. A right adrenal pheochromocytoma was found and excised. The neoplastic cell population was immunohistochemically shown to contain VIP, SRIF, and calcitonin. Gross, histologic, and immunohistochemical evaluation of the pancreas revealed no abnormalities, whereas a marked hyperplasia of the gastrin-producing cells of the gastric antral mucosa was demonstrated. Postoperatively, the patient recovered from his symptoms and the plasma hormone levels returned to normal values. The clinical and histogenetic implications of this most unusual tumor of neural crest derivatives are discussed.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Calcitonin; Gastrins; Histocytochemistry; Hormones, Ectopic; Humans; Immunoenzyme Techniques; Male; Pheochromocytoma; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

A patient presenting clinically with the glucagonoma syndrome had high plasma glucagon levels (1920 ng/l) and at laparotomy, a pancreatic islet cell tumour was removed. The tumour was dispersed and placed in culture where it remained viable for 63 days. The tumour cells secreted immunoreactive (IR) glucagon at levels up to 2400 ng/l as detected by a C-terminal glucagon specific antibody and 85 400 ngequiv./l as measured by an N-terminal glucagon specific antibody. The difference between these two levels was attributed to the presence of different molecular forms of glucagon measured with the N-terminal specific antibody. IR insulin (up to 302 mU/l) and IR somatostatin (up to 2500 ng/l) were also detected. There was no direct or inverse correlation between different hormone levels. Small but significant levels of N-terminal and C-terminal vasoactive intestinal peptide (VIP) were detected in some cultures but there was no evidence of gastrin or ACTH. Glucagon and somatostatin secretion persisted for the duration of the culture (63 days) but insulin concentrations declined. Incubation of cultures with somatostatin (1 ng/ml) caused a 75% decrease in glucagon levels, while insulin (1000 mU/l) produced a 70% inhibition of somatostatin.

Topics: Adenoma, Islet Cell; Cells, Cultured; Female; Fluorescent Antibody Technique; Gastrins; Glucagon; Glucagonoma; Humans; Immunoenzyme Techniques; Insulin; Insulin Secretion; Kinetics; Middle Aged; Neurotensin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

We studied a patient with a very small somatostatinoma that arose from the prominence of the orifice of the duct of Santorini. The patient presented clinically with epigastric discomfort, marked loss of weight, diarrhea, exertional dyspnea, and chest pain. He flushed intermittently and had occasional tachycardia and hypertension. Levels of serum serotonin and urinary 5-hydroxyindoleacetic acid were normal. A small ampullary tumor was resected and identified by immunohistochemical staining to be a somatostatinoma. The patient had gained 6.75 kg and was essentially free of symptoms 16 months after surgery.

Topics: Adenoma, Islet Cell; Gastrins; Humans; Male; Middle Aged; Neoplastic Stem Cells; Pancreatic Ducts; Pancreatic Neoplasms; Serotonin; Somatostatin; Somatostatinoma

A patient with a calcifying chronic pancreatitis was found to have a neuroendocrine islet cell tumour (a previously unreported association). The tumour secreted both gastrin and ACTH leading to clinical manifestations of both the Zollinger-Ellison syndrome and Cushing's syndrome.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Aged; Calcinosis; Chronic Disease; Gastrins; Humans; Male; Pancreatic Neoplasms; Pancreatitis; Zollinger-Ellison Syndrome

One hundred twenty-seven insulinomas from 95 cases (1 malignant and 94 benign) were studied pathologically. Thirty-six tumors (35 cases) were examined by electron microscopy. Typical beta-cell secretory granules of crystalloid-form cores and/or atypical secretory granules were discerned in all tumors examined. A new type of secretory granule, with high electron-dense crystalloid-form cores and moderate electron-dense granular substance filling the space between the core and the limiting membrane, were observed in two cases. Among 68 insulinomas (67 cases) subjected to immunocytochemical investigations with ten peptide hormones (insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, motilin, secretin, vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and neurotensin), 42 were found to be multihormonal, varying from two to four peptides secreted. The hormones contained were insulin, glucagon, PP, somatostatin, and gastrin in different combinations. One patient had hyperinsulinemia and hypergastrinemia concurrently, and two islet tumors were excised at an interval of 10 months. Both electron microscopy and immunocytochemistry confirmed the presence of beta- and alpha-cells in the first tumor, whereas the second tumor revealed only G-cells by electron microscopy, and G- and beta-cells on immunocytochemical staining. The morphologic and immunocytochemical characteristics of the insulinomas in this series are discussed.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Cytoplasmic Granules; Female; Gastrins; Hormones; Humans; Immunoenzyme Techniques; Insulin; Insulinoma; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.

Topics: Adenoma, Islet Cell; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastrins; Humans; Middle Aged; Pancreatic Neoplasms; Streptozocin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Dacarbazine; Gastrins; Glucagon; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

A young woman with acromegaly and Zollinger-Ellison syndrome associated with a GH-releasing factor (GRF)- and gastrin-secreting metastatic islet cell carcinoma was studied by means of specific antisera which recognize various regions of the GRF molecule. Using specific immunohistochemical techniques, the tumor cells were shown to contain GRF, gastrin, and gastrin-releasing peptide, but not GH. During a 4-h period, plasma GRF levels averaged 5.6 +/- 1.4 ng/ml (+/- SD), while GH levels averaged 148 +/- 71 ng/ml. GH secretion was pulsatile and increased after TRH administration. GRF RIAs may be useful in establishing the diagnosis of acromegaly secondary to the ectopic secretion of GRF.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

37 patients suffering from apudomas of the pancreas are reported (18 insulinomas, 6 isletcell-hyperplasias, 9 Zollinger-Ellison syndroms, 1 glucagonoma, 3 without hormone production). In preoperative localization computerized tomography and angiography were the best with 65% positive findings. Insulinomas were enucleated, all free of recidives. 50% of operated isletcell hyperplasias had a postoperative resisting hyperinsulinism. Either gastrectomy or tumour enucleation was performed in the Zollinger-Ellison syndrome. The five-years survival rate was 43%.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Female; Follow-Up Studies; Gastrectomy; Gastrins; Glucagon; Humans; Hyperplasia; Insulin; Insulinoma; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Stomach Neoplasms; Zollinger-Ellison Syndrome

Four cases involving cystic endocrine neoplasms of the pancreas and liver are reported. Because of their rich collateral blood supply, islet cell tumors of the pancreas, even if large in size, rarely undergo central or cystic degeneration. However, failure to appreciate that a small percentage of these neoplasms may mimic benign pancreatic pseudocysts by their clinical and radiological appearance can lead to inappropriate surgical therapy. Ultrasound, computerized tomography, and/or angiography are rarely helpful in distinguishing between benign and neoplastic cysts. The definitive diagnosis can be made with assurance only by obtaining a generous biopsy of the cyst wall or any intracystic excrescences for histologic examination. Functional cystic tumors of the pancreas or liver should be excised totally whenever possible, and efforts should be made to remove as much of the tumor mass as possible even when a curative resection cannot be accomplished. Internal drainage may be acceptable as palliation for large, unresectable tumors.

Topics: Adenoma, Islet Cell; Adult; Cysts; Diagnosis, Differential; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Cyst; Pancreatic Neoplasms; Tomography, X-Ray Computed

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Glucagon; Humans; Hyperplasia; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Serotonin; Somatostatin; Staining and Labeling; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Exploratory laparotomy and a search for gastrinomas was performed in 52 patients with the Zollinger-Ellison syndrome (ZES). Gastrinoma tissue was resected in 11 patients (21%), 6 (12%) of whom appear to have been cured. After surgery, serum gastrin levels in these six patients have remained normal from 10 months to 10 years. In the 46 other patients, tumor was unresectable because of metastases or multiple primary tumors (21 patients; 40%) or inability to find the tumor at laparotomy (21 patients; 40%). Multiple pancreatic islet cell adenomata were found in six of seven patients with multiple endocrine neoplasia (MEN), indicating that patients with this condition usually have diffuse involvement of the pancreas. The results of CT scans correlated with findings at laparotomy in 13 of 16 patients. The smallest tumor detected by CT scans was 1 cm in diameter. CT technology is more accurate in finding gastrinomas now than in the past and has a useful role in preoperative evaluation. The possibility of resection should be seriously considered in every patient with Zollinger-Ellison syndrome. Abdominal CT scans, transhepatic portal venous sampling, and laparotomy should be used to find the tumor and to determine whether it is resectable. Using presently available methods, it should be possible to cure about 25% of patients with gastrinomas who do not have MEN and over 70% of those without MEN who appear to have a solitary tumor. Total pancreatectomy may be necessary to cure some patients with MEN, but that operation is rarely justified. The morbidity and mortality of surgical attempts at curing this disease have become minimal; we have had no deaths or serious complications following such operations in over 10 yrs. Total gastrectomy and indefinite use of H2-receptor blocking agents are the therapeutic options for patients with unresectable gastrinomas. Because H2-receptor blocking agents fail to control acid secretion in many patients after several yrs of therapy, total gastrectomy is indicated in a large proportion of patients whose tumors cannot be resected. Total gastrectomy in patients with ZES is also safe using current techniques; our last death following this operation for ZES occurred 15 yrs ago.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Postoperative Complications; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Use of commercial immunoperoxidase kits for the study of gastrin, glucagon, insulin, and somatostatin production in 13 islet-cell tumors was assessed. Kits save time in preparation and technic, are convenient and easy to use, and are economical for occasional tests. Results are reproducible, with crisp immunostain, minimal background staining, and high sensitivity so that interpretation is easy. The relevant hormone was specifically identified in seven symptomatic tumors. Of six asymptomatic tumors, five showed strongly positive glucagon immunostain and one somatostatin. Nine tumors, in addition, contained somatostatin. Three tumors produced a third hormone. Use of kits can prove expensive for large numbers of tests. Reagents supplied were of unknown dilution and usually insufficient to run negative controls concurrently. Fading of immunostain was noticed after six months of storage.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Immunoenzyme Techniques; Insulin; Pancreatic Neoplasms; Reagent Kits, Diagnostic; Retrospective Studies; Somatostatin

Immunocytochemical stains for various pancreatic hormones were performed on 77 pancreatic endocrine tumors from 59 patients [17 with hypoglycemia, three with glucagonoma syndrome, 18 were Zollinger-Ellison syndrome, six with WDHA (watery, diarrhea, hypokalemia, and achlorhydria) syndrome and 15 without endocrine symptoms]. In all tumors that caused either hypoglycemia or glucagonoma syndrome, insulin and glucagon were respectively identified. On the other hand, only 10 tumors from 18 patients with Zollinger-Ellison syndrome were positive for gastrin, and only four of six patients with WDHA syndrome had a vasoactive intestinal peptides-positive tumor. Ten of 15 clinically silent tumors contained hormone-producing cells but without a consistent pattern. Ten neoplasms were negative for all hormones tested. Twenty-six tumors showed positively for more than one hormone and usually one cell type predominated. Four patients had multiple tumors which showed variation in the architecture and cellular composition. The tumors were classified into three major histopathologic groups: solid, gyriform, and glandular. The correlation between the pattern of growth and the hormonal production was generally poor. However, a pure gyriform pattern was often associated with insulin production, and glandular differentiation was commonly seen in tumors associated with Zollinger-Ellison syndrome. This study demonstrates the reliability of the immunocytochemical method for the specific identification of cell types in pancreatic endocrine tumors.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Female; Gastrins; Glucagon; Hormones; Humans; Immunoenzyme Techniques; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Somatostatin; Vasoactive Intestinal Peptide

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Topics: Adenoma, Islet Cell; Anemia; Body Weight; Dermatitis; Gastrins; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Syndrome

Percutaneous transhepatic sampling of blood in the portal venous system (TPVS) was used to; (1) localize hormone secreting tumors and help in differentiating tumors from diffuse disease (nesideoblastosis and hyperplasia with adenomata) in 9 patients with fasting hypoglycemia and hyperinsulinism, and (2) study the concentration an distribution of the immunoreactive peptides: insulin (IRI), gastrin (IG), glucagon (IRG), pancreatic polypeptide (hPP), and somatostatin (SRIF-LI), in the venous drainage of the uninvolved portion of the pancreas and GI tract. Localized elevations of IRI (64-920 microunits/ml) predicted tumor localization in 6 patients with single tumors that were not demonstrable angiographically. In one patient with nesideoblastosis and another with islet cell hyperplasia with adenoma, elevated IRI concentrations at multiple locations suggested a diffuse or multicentric process. Elevations of SRIF-LI in the same region as IRI elevations in one patient and of IRG in another patient suggested that these tumor produced two hormones. Some problems in the interpretation of portal venous insulin concentrations are discussed. The locations of maximum portal venous system plasma concentrations and portal-arterial gradients (mean +/- SE pg/ml) in five patients with small single insulinomas were: IG, gastrocolic trunk (126 +/- 27, 46 +/- 22); IRG, proximal splenic vein (130 +/- 30, 47 +/- 13) and gastrocolic trunk (131 +/- 23, 60 +/- 13); hPP, portal vein (164 +/- 48, 49 +/- 22); SRIF-LI, superior mesenteric vein (186 +/- 50, 57 +/- 20) and gastrocolic trunk (178 +/- 59, 55 +/- 21). It is concluded; (1) TPVS can be used successfully to localize single insulin-secreting tumors of the pancreas and to help distinguish them from diffuse disease but problems in such differentiation do occur, (2) circulating SRIF-LI and IRG are derived from both the pancreas and the gut, IG predominantly from the proximal gut and hPP from the head of the pancreas, and (3) The data provide new information for the interpretation of portal insulin concentrations in patients with organic hyperinsulinism and of hormone concentrations for localization of peptide-producing tumors of the pancreas other than insulinomas.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Female; Gastrins; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Portal Vein; Somatostatin

A 61-year-old man with a malignant endocrine pancreatic tumour, so-called "non-functioning" islet cell tumour, is described. The tumour consisted of enterochromaffin-like cells with positive immunocytochemistry for gastrin, glucagon and VIP, but neither of these or other peptides were elevated in the circulation. Elevated serum levels of HCG-alpha and HCG-beta subunits were found. They seemed to be valuable tumour markers during cytotoxic therapy.

Topics: Adenoma, Islet Cell; Antineoplastic Agents; Chorionic Gonadotropin; Female; Gastrins; Glucagon; Humans; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Insulinoma, glucagonoma, gastrinoma (Zollinger-Ellison syndrome), vipoma, somatostatinoma and a tumor that secretes human pancreatic polypeptide are the primary endocrine-secreting tumors of the pancreas. hormones are produced by specific tumor cell types and cause a variety of dramatic clinical pictures. Diagnosis often requires hormone assays. Computerized tomography may be helpful. Definitive surgical treatment is possible, but metastases may be present.

Topics: Adenoma, Islet Cell; Apudoma; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

An islet cell carcinoma of the pancreas is described in a 68-year old woman which clinically produced Zollinger-Ellison syndrome and, later in its course, Cushing syndrome. The tumor was found to contain gastrin, ACTH, alpha-endorphin, somatostatin and calcitonin, by the immunoperoxidase technic. Electron microscopy revealed a single tumor cell type containing secretory granules of variable size, morphology and electron density. It appears that a single tumor cell population produced all five hormones and caused a transition in clinical symptomatology, while undergoing no change in morphology.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Aged; Calcitonin; Cushing Syndrome; Endorphins; Female; Gastrins; Hormones, Ectopic; Humans; Immunoenzyme Techniques; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Somatostatin; Zollinger-Ellison Syndrome

The main clinical signs of three dogs with Zollinger-Ellison syndrome were vomiting, diarrhoea, poor appetite and weight loss. The diagnosis was confirmed by histological examination and by gastrin immunocytochemistry. Gastrin was extracted from pancreatic tumours of two dogs. Gastrin-component III predominated in one dog while gastrin-component II and gastrin-component III were demonstrated in almost equal amounts in the other dog. In one dog serum gastrin concentration was high. Postmortem examination revealed pancreatic tumours in all three dogs and metastases in the regional lymph nodes and liver in two. The pancreatic tumours contained three patterns of growth: solid, trabecular and acinar. Electron microscopy of liver metastases showed cells with secretory granules. In all three dogs there was an erosive oesophagitis and thick gastric mucosa caused mainly by glandular proliferation. Two dogs had erosions and ulcers in the duodenum, one also in the first part of the jejunum. Villous atrophy and cellular infiltration of the duodenal mucosa were found in all dogs.

Topics: Adenoma, Islet Cell; Animals; Dog Diseases; Dogs; Esophagus; Female; Gastrins; Intestines; Male; Pancreatic Neoplasms; Stomach; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Pancreatic Hormones; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Humans; Radioimmunoassay; Secretin

A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypergastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had unresectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long-term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperatively to control the gastric hypersecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives.

Topics: Adenoma, Islet Cell; Cimetidine; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Jejunal Diseases; Pancreatectomy; Pancreatic Neoplasms; Peptic Ulcer; Vagotomy

The effect of intravenous secretin on plasma immunoreactive gastrin is presumed to improve diagnostic accuracy in patients with a gastrinoma. To investigate this further, the secretin provocation test was performed in control patients (n = 10), patients with a primary duodenal ulcer (n = 10), patients who had previously had surgery for a duodenal ulcer (n = 20), patients with symptomatic recurrent peptic ulceration (n = 50) and 2 patients with a histologically proved gastrinoma. It was found that the secretin test gave a false positive result in 3 out of 10 symptomatic duodenal ulcer patients, 2 out of 20 patients who had had previous duodenal ulcer surgery and were now asymptomatic and 15 out of 50 patients with recurrent peptic ulceration. Both gastrinoma patients had positive secretin tests but there were no obvious criteria that separated the gastrin response of a gastrinoma patient from those with primary or recurrent peptic ulceration. It is concluded that the secretin test is probably of little value in both the screening and the diagnosis of a gastrinoma.

Topics: Adenoma, Islet Cell; Diagnosis, Differential; Duodenal Ulcer; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Recurrence; Secretin

It has now been well established that the ulcerogenic syndrome associated with non-beta islet cell tumors of the pancreas is due to excess gastrin release and consequent marked gastric acid hypersecretion. The clinical manifestations may be similar to, but are often more severe and recurrent than, common peptic ulcer. The diagnosis of gastrinoma in patients with this clinical syndrome can be established principally by demonstration of fasting hypergastrinemia, and by application of provocative tests with measurement of serum gastrin in response to intravenous calcium infusion, intravenous secretin injection and feeding of a standard meal. Gastrinomas are usually located within the pancreas, are often multifocal and metastatic, but may be primary in non-pancreatic sites. There is substantial heterogeneity in the molecular forms of circulating and gastrinoma gastrin. Although hypergastrinemia is characteristic of gastrinoma, serum gastrin levels may be increased in disorders other than gastrinoma. Techniques are available to document the presence of gastrin in islet cell tumors and, thereby, to establish these as gastrinomas.

Topics: Adenoma, Islet Cell; Calcium; Diagnosis, Differential; Duodenum; Fasting; Gastrins; Humans; Injections, Intravenous; Pancreas; Secretin; Stomach; Zollinger-Ellison Syndrome

A patient initially showed symptoms of peptic ulcer disease in 1953 and was later found to have hypercalcemia and hyperparathyroidism. Peptic ulcer symptoms persisted after parathyroidectomy, and results of studies provided evidence of the Zollinger-Ellison syndrome. Evaluation of the patient's family showed a classic pattern of multiple endocrine adenomatosis type 1. The patient underwent total gastrectomy and excision of a gastrin cell adenoma in 1971 with relief of symptoms, but with persistent hypergastrinemia. He remained in good health until January 1976, when symptoms of hypoglycemia developed. Results of laboratory studies were compatible with the diagnosis of a pancreatic beta-cell adenoma. At the time of operation, an adenoma of the head of the pancreas was found. The tumor was excised; no other metastatic tumors were found. The tumor was compatible with a beta-cell adenoma and was found to contain high concentrations of insulin; there was no important amount of gastrin. Symptoms of hypoglycemia have entirely disappeared.

Topics: Adenoma; Adenoma, Islet Cell; Gastrins; Humans; Hypoglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Hypoglycemia; Pancreatic Neoplasms; Skin Manifestations; Zollinger-Ellison Syndrome

A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Diarrhea; Endocrine System Diseases; Gastrins; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Parathyroid Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Conventional or electron microscopy can contribute significantly to the diagnosis of pancreatic endocrine tumours. These techniques, however, are of limited value for the classification of the tumours, which should take both clinical and morphological findings into account. In this paper a classification based on both the clinical features and on the content of peptide hormone-producing cells in the tumours is presented.

Topics: Adenoma, Islet Cell; Cushing Syndrome; Gastrins; Glucagon; Humans; Malignant Carcinoid Syndrome; Pancreatic Neoplasms; Somatostatin; Zollinger-Ellison Syndrome

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Intestinal Neoplasms; Motilin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

The role of human pancreatic-polypeptide in endocrine tumours of the pancreas is reviewed. Pancreatic-polypeptide may be involved in 3 different ways: 1. In cases with pure PP producing tumours. 2. In mixed endocrine tumours containing PP cells. 3. In cases with PP cell hyperplasia in normal pancreatic tissue associated with endocrine pancreatic tumours as VIP-omas, insulinomas, and glucagonomas. PP does not seem to serve as a general marker for endocrine tumours of the pancreas, but PP determinations are useful in patients wbith watery diarrhoea syndromes, because such syndromes may be associated with tumours that contain PP cells. Large molecular forms of PP occur in plasma from patients with endocrine tumours and high PP concentrations, but may also be found in other groups of patients. It is suggested that an atropin-suppression test could be of diagnostic value in revealing patients with increased serum concentrations of PP from other causes than vagal stimulation of normal PP cells.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrins; Glucagon; Humans; Hyperplasia; Molecular Weight; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Syndrome; Zollinger-Ellison Syndrome

Gastro-entero-pancreatic (GEP) and bronchial endocrine tumours have been studied by immunohistochemistry using specific antisera against a variety of hormonal and neuronal peptides. In gastrinomas numerous tumour cells were found to contain GH-like immunoreactivity. These cells were identical with those storing gastrin. Gastrinomas as a rule were extremely heterogeneous containing a variety of minority cell populations, including CCK immunoreactive cells and neurotensin immunoreactive cells. Glucagonoma cells were found to store GIP-like material in addition to glucagon. In some insulinomas calcitonin-like material was encountered in the insulin producing tumour cells. In both glucagonomas and insulinomas other pancreatic endocrine cell types constituted minority cell populations. One intestinal somatostatinoma contained gastrin cells as a minority cell population. Bronchial endocrine tumours contained scattered cells displaying ACTH-like or enkephalin-like immunoreactivity. Two such tumours in addition contained cells displaying neurophysin immunoreactivity.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Cholecystokinin; Enkephalins; Fluorescent Antibody Technique; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Neurophysins; Pancreatic Neoplasms; Serotonin; Somatostatin; Stomach Neoplasms; Zollinger-Ellison Syndrome

A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumors, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrectomy; Gastrins; Glucagon; Histamine H2 Antagonists; Humans; Neoplasm Metastasis; Pancreatectomy; Pancreatic Neoplasms; Statistics as Topic; Syndrome; Zollinger-Ellison Syndrome

A patient is described who had a malignant pancreatic islet cell apudoma secreting corticotrophin (ACTH) and melanocyte-stimulating hormone (MSH), both of which were clinically active, and very large quantities of immunoreactive gastrins, which were biologically active but clinically silent (normal gastric acid secretion and no peptic ulceration). The presence of parietal cell antibodies, with no increase in the plasma concentrations of hormones which can inhibit gastric acid secretion (secretin, GIP and VIP), suggests that many of the of the parietal cells may have been blocked by the autoantibodies.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Apudoma; Gastrins; Humans; Male; Melanocyte-Stimulating Hormones; Pancreatic Neoplasms

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Hormones, Ectopic; Humans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide

Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from "insulinoma" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Diagnostic Errors; Female; Gastrins; Humans; Hypoglycemia; Male; Middle Aged; Pancreatic Neoplasms; Proinsulin; Time Factors

Topics: Adenoma, Islet Cell; Adult; Aged; Female; Gastrins; Glucagon; Humans; Infant; Insulin; Insulin Secretion; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Somatostatin

Topics: Adenoma, Islet Cell; Gastrins; Humans; Pancreatic Neoplasms; Secretin

Thirty pancreatic islet cell tumours were histologically classified and analysed for their possible peptide hormone content using the immunohistoperoxidase method. Seven tumours contained insulin, six tumours contained gastrin and eight tumours contained glucagon. One tumour contained all three hormones. In the insulin and gastrin-containing tumours, the cells were usually arranged in solid nests of cells, with tubular and acinar formations in about half the cases. In the glucagon-containing tumours the cells were mainly arranged in anastomosing ribbons consisting of one of two layers of small cells. Most of the hormone-containing tumours were argyrophilic using Grimelius' silver reaction. All but one of the glucagon-containing tumours were incidental findings at autopsy. About half of the other tumours had metastasized. It is concluded that a relation exists between the histological pattern of growth and immunohistochemically defined endocrine function of pancreatic islet cell tumours.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Immunoenzyme Techniques; Insulin; Neoplasm Metastasis; Pancreatic Neoplasms

Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumours, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.

Topics: Adenoma, Islet Cell; Gastrins; Germany, West; Glucagon; Insulin; Pancreatic Neoplasms

To evaluate its potential as an alternative to angiography in the diagnosis of pancreatic tumors, we performed selective vein catheterization for hormone assay on 11 patients with islet cell tumors and islet cell hyperplasias. In all patients, the abnormal pancreatic tissue was correctly localized preoperatively by this method.

Topics: Adenoma, Islet Cell; Aged; Catheterization; Female; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Phlebography

Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Bromocriptine; Gastrins; Growth Hormone; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas.

Topics: Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Antigen-Antibody Reactions; Carcinoma; Female; Gastrins; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreas; Pancreatic Hormones; Proinsulin; Tolbutamide

A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.

Topics: Adenoma, Islet Cell; Female; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by "active" or "Stem cell" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.

Topics: Adenoma, Islet Cell; Animals; Cats; Cell Differentiation; Dogs; Gastrins; Glucagon; Guinea Pigs; Humans; Insulin; Islets of Langerhans; Microscopy, Electron; Pancreatic Neoplasms; Serotonin; Somatostatin; Swine

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Carcinoma, Small Cell; Gastrins; Gastrointestinal Neoplasms; Glucagon; Humans; Intestinal Mucosa; Islets of Langerhans; Neurosecretory Systems; Paraneoplastic Endocrine Syndromes; Peptides

Topics: Adenoma, Islet Cell; Aged; Dehydration; Diarrhea; Female; Gastrins; Humans; Hypercalcemia; Hypokalemia; Indomethacin; Prostaglandins E; Prostaglandins F; Syndrome

A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged.

Topics: Adenoma, Islet Cell; Adult; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Pancreatic Neoplasms; Remission, Spontaneous; Secretory Rate; Zollinger-Ellison Syndrome

In 33 patients studied with endocrine neoplasms of the pancreas more than half the tumours contained pancreatic polypeptide (P.P.) producing cells, and a high radioimmunoassayable concentration of P.P. was found in the tumour extracts. Plasma was available from 28 patients, and very high circulating P.P. concentrations were found in 18. The presence of P.P. in hepatic and lymphnode metastases indicates that its production by the primary neoplasm cannot be ascribed to incidental adherence of normal P.P. cells. Measurements of plasma P.P. levels should be a new aid to diagnosis of pancreatic tumours.

Topics: Adenoma, Islet Cell; Gastrins; Gastrointestinal Hormones; Glucagon; Histocytochemistry; Humans; Insulin; Insulin Secretion; Pancreas; Pancreatic Hormones; Pancreatic Neoplasms; Peptides; Radioimmunoassay; Tissue Extracts

In a first step of our investigation the staining characteristics, especially the argyrophilia and metachromasia, of immunohistologically identified endocrine cells of the pancreatic islets and of the gastroduodenal mucosa were tested. These staining characteristics were then examined on insulinomas and gastrinomas. Contrary to normal B cells which generally react positively with aldehyde fuchsin and pseudoisocyanine but not argyrophilic with the Grimelius method, the neoplastic B cells give inconsistent results with conventional staining methods. Yet neoplastic B cells often show argyrophilic structures. Immunohistologically, most benign insulinomas are rich in insulin-containing cells, whereas in malignant types such cells are rare. The carcinomas, however, show a typical and distinct Grimelius argyrophilia. The tumor cells of gastrinomas are Grimelius argyrophilic and slightly metachromatic, as normal G cells, yet, contrary to A1 cells, they are only exceptionally stainable with the Hellerström method. Despite the great number of Grimelius positive tumor cells, generally only a few reacted with antigastrin serum. Nevertheless, the immunohistology is the most reliable method for the diagnosis of gastrinomas. Electron microscopic results are often difficult to interpret, since gastrinomas, as well as undifferentiated or malignant insulinomas, may predominantly contain atypical secretion granules.

Topics: Adenoma, Islet Cell; Duodenum; Gastric Mucosa; Gastrins; Humans; Immunologic Techniques; Insulin; Intestinal Mucosa; Microscopy, Electron; Staining and Labeling; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Peptides

What is considered to represent the fourth case of perforated jejunal ulcer in association with the Zollinger-Ellison syndrome reported in the literature is discussed. Although documented in the original paper by Zollinger and Ellison, this remains a notably rare complication. Generalized peritonitis and related pathophysiological phenomena make initial definitive correction of the ulcer diathesis an extremely riskly undertaking and ill-advised. We submit that primary ulcer resection followed by total gastrectomy when the patient becomes a more suitable operative risk is the preferred method of management. The literature would appear to support this clinical view.

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Gastrectomy; Gastrins; Humans; Jejunum; Male; Middle Aged; Peptic Ulcer Perforation; Zollinger-Ellison Syndrome

As streptozocin has a toxic effect on gastrin producing cells in some patients with gastrinomas, the action of the drug upon normal gastrin release was evaluated in patients with carcinoid tumours (n=6) and malignant insulinomas (n=2). No acute effects were recorded in 22 instances where gastrin levels were followed during the first 24 hours after infusion of streptozocin. When gastrin levels were compared throughout a course of repeated infusions during months a significant increase was noted. Concentrations were doubled after 6 g streptozocin given during a four months period, and tripled after 10 g in nine months period. One patients developed bleeding duodenal ulcer after a total dose of 6 g. It is concluded that streptozocin does not damage normal G cells, but by some action seems to stimulate gastrin relase. Peptic ulceration may be an important side effect during a long term treatment.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Female; Gastrins; Humans; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Stomach Neoplasms; Streptozocin

A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal "carcinoid-islet cell tumor." Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. "Carcinoidislet cell tumors," like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques.

Topics: Adenoma, Islet Cell; Aged; Carcinoid Tumor; Duodenal Neoplasms; Gastrins; Humans; Male; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Dog Diseases; Dogs; Gastrins; Male; Pancreatic Neoplasms; Peptic Ulcer

Topics: Adenoma, Islet Cell; Animals; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Zollinger-Ellison Syndrome

Angiographic findings in one giant cell carcinoma, one cystadenocarcinoma, one poorly vascularized mucinous cystadenocarcinoma, as well as in two avascular (gastrin- and glucagon-producing) islet-cell tumors of the pancreas are described. Two hypervascularized islet-cell tumors are presented for comparison and a case of tumorous chronic pancreatitis in a child is reported because ot its rarity. The aggressiveness of the giant cell carcinoma of the pancreas was demonstrated by its expansive growth. In the case of cystadenocarcinoma angiography revealed the tumor with hepatic metastases not diagnosed at explorative laparotomy. The relative hypovascularity in the case of mucinous cystadenocarcinoma was unusual. Both avascular islet-cell tumors simulated a pancreatic pseudocyst and the final diagnosis was made only by immunoassay. Chronic pancreatitis in a child presented with marked hypervascularization.

Topics: Adenoma, Islet Cell; Adult; Aged; Angiography; Carcinoma; Celiac Artery; Chronic Disease; Contrast Media; Cystadenoma; Diagnosis, Differential; Female; Gastrins; Glucagon; Hepatic Artery; Humans; Male; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatitis; Zollinger-Ellison Syndrome

The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Diarrhea; Female; Gastrins; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.

Topics: Adenoma, Islet Cell; Fasting; Fluorouracil; Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Postgastrectomy Syndromes; Prognosis; Stomach Neoplasms; Streptozocin; Tubercidin

After removal of two large pancreactic insulinomas, although the presenting spontaneous hypoglycaemia was eliminated, severe and persisting haematemesis and melaena supervened with a rise in serum gastrin. The patient had multiple endocrine adenopathy (pituitary, parathyroids and islet cells), but no evidence of a pancreatic gastrin-producing tumour. After emergency gastric operation for the bleeding, the serum gastrin remained high until the hypercalcaemia and hyperparathyroidism had been corrected by subtotal parathyroidectomy. Immunofluorescence studies showed gastrin in the parathyroid tissue.

Topics: Adenoma, Islet Cell; Endocrine System Diseases; Fluorescent Antibody Technique; Gastrins; Glucose Tolerance Test; Hormones, Ectopic; Humans; Hyperparathyroidism; Hypoglycemia; Male; Middle Aged; Pancreatic Neoplasms; Parathyroid Glands

Topics: Adenoma, Islet Cell; Depression, Chemical; Female; Gastrins; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Middle Aged; Pancreatic Neoplasms; Somatostatin

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Dehydration; Female; Gastrins; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Syndrome; Zollinger-Ellison Syndrome

Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cell Transformation, Neoplastic; Cytoplasmic Granules; Dehydration; Female; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Intestines; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Peptides; Syndrome

The neurosecretory cells of the hypothalamus, and the cells of the pituitary gland and the pineal, are here grouped together as a central neuroendocrine division of the APUD series. The larger, peripheral division comprises the remainder of the original series. All the cells are proven or presumptive derivatives of neuroectoderm so that, with the present exception of the parathyroid gland and its products, peptide hormone endocrinology becomes neuroendocrinology. It follows that the pathology of the APUD cell series must be regarded as neuroendocrine and it is suggested that it can best be expressed by the term neurocristopathy (Bolande, 1974). Tumours of the series, properly neurocristomas, are preferably called apudomas because their common cytochemical (APUD) and ultrastructural characteristics provide the pathologist with a ready means of diagnosis.

Topics: Adenoma, Islet Cell; Amines; Animals; Biological Evolution; Calcitonin; Carcinoid Tumor; Cushing Syndrome; Dehydration; Ectoderm; Endocrine System Diseases; Ganglia; Gastrins; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neoplasms, Multiple Primary; Neurosecretory Systems; Paraneoplastic Endocrine Syndromes; Peptide Biosynthesis; Secretin; Terminology as Topic; Vertebrates; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Diarrhea; Female; Gastric Juice; Gastrins; Glucose; Humans; Hypercalcemia; Male; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin.

Topics: Adenoma, Islet Cell; Asparaginase; Gastrins; Humans; Hypoglycemia; Insulin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms

Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.

Topics: Acromegaly; Adenoma, Islet Cell; Administration, Oral; Blood Glucose; Female; Gastrins; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Male; Pituitary Neoplasms; Prolactin; Somatostatin; Time Factors

Topics: Adenoma, Islet Cell; Adult; Gastrins; Humans; Male; Pancreatic Neoplasms; Time Factors; Zollinger-Ellison Syndrome

In a healthy subject infusions of either secretion or glucagon caused no diarrhea. A combinations of gastrin and glucagon induced severe watery diarrhea immediately after the end of the 3 hour infusion. No diarrhea occurred from the combination of secretin and gastrin.

Topics: Adenoma, Islet Cell; Adolescent; Dehydration; Diarrhea; Drug Combinations; Gastrins; Glucagon; Humans; Secretin

Topics: Adenoma, Islet Cell; Adult; Aged; Dehydration; Diagnosis, Differential; Diarrhea; Female; Fluorescent Antibody Technique; Gastrins; Humans; Hypokalemia; Islets of Langerhans; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Radioimmunoassay; Staining and Labeling; Syndrome; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Age Factors; Calcium; Child; Fasting; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Diarrhea; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Administration, Oral; Aged; Gastrectomy; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Insulin Secretion; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Antibodies; Gastrins; Humans; Molecular Weight; Pancreatic Neoplasms

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Diarrhea; Female; Gastrins; Humans; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenocarcinoma; Adenoma, Islet Cell; Calcium; Child; Duodenal Diseases; Gastric Juice; Gastrins; Humans; Lymphatic Metastasis; Male; Pancreatic Neoplasms; Radiography; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Asparaginase; Child; Child, Preschool; Cushing Syndrome; Female; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Phenytoin; Secretin; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Follow-Up Studies; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hyperplasia; Lymph Node Excision; Lymphatic Metastasis; Male; Methods; Pancreatic Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Calcium; Chlorides; Diarrhea; Follow-Up Studies; Gastric Juice; Gastrins; Humans; Lymph Nodes; Male; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Potassium; Sodium; Stimulation, Chemical; Syndrome; Time Factors

Topics: Adenoma, Islet Cell; Adult; Blood Urea Nitrogen; Calcium; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Angiography; Carcinoid Tumor; Celiac Artery; Cytoplasmic Granules; Duodenal Neoplasms; Female; Gastrins; Humans; Insulin; Insulin Secretion; Male; Mesenteric Arteries; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Serotonin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Radioimmunoassay; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Aminoglutethimide; Gastrins; Glucagon; Hormones, Ectopic; Humans; Male; Metyrapone; Microscopy, Electron; Neoplasm Metastasis; Radioimmunoassay; Streptozocin

Topics: Adenoma, Islet Cell; Calcium; Endocrine Glands; Gastric Acidity Determination; Gastrins; Humans; Hyperparathyroidism, Secondary; Pancreatic Neoplasms; Secretory Rate; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Acidosis; Adenoma, Islet Cell; Adult; Autopsy; Diarrhea; Female; Fluorescent Antibody Technique; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hypokalemia; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Peptides; Radioimmunoassay; Secretin; Syndrome

Topics: Adenoma, Islet Cell; Adult; Duodenal Neoplasms; Female; Gastrectomy; Gastrins; Humans; Lymphatic Metastasis; Male; Middle Aged; Radioimmunoassay; Veins; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Calcium; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism; Hyperplasia; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Calcium; Diagnosis, Differential; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Aged; Biopsy; Carcinoid Tumor; Female; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Microscopy, Electron; Middle Aged; Pedigree; Pituitary Neoplasms; Prospective Studies; Pyloric Antrum; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Biological Transport, Active; Diarrhea; Gastrins; Glucagon; Hormones, Ectopic; Humans; Jejunum; Peptides; Secretin; Water-Electrolyte Balance

Topics: Adenoma, Islet Cell; Diarrhea; Fluorouracil; Follow-Up Studies; Gastrectomy; Gastrins; Glucagon; Humans; Immunoassay; Insulin; Insulin Secretion; Neoplasm Metastasis; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Streptozocin

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Diazoxide; Female; Gastric Mucosa; Gastrins; Glucagon; Glucose Tolerance Test; Humans; Hypercalcemia; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pedigree; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Diarrhea; Female; Gastrins; Humans; Hyperglycemia; Hyperinsulinism; Hypokalemia; Insulin; Insulin Secretion; Kidney Diseases; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Adenoma; Adenoma, Islet Cell; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Child; Child, Preschool; Female; Gastrins; Humans; Infant; Insulin; Insulin Secretion; Male; Melanocyte-Stimulating Hormones; Middle Aged; Pancreatic Neoplasms; Serotonin; Zollinger-Ellison Syndrome

A patient with a multiple-hormone-producing islet cell carcinoma, who had previously been successfully treated with streptozotocin, was given three further infusions of this drug because of the redevelopment of gastric hypersecretion. Although some evidence of damage to the gastrinsecreting cells was obtained, the fasting plasma gastrin was not significantly altered and the patient died from a perforated duodenal ulcer. Serum insulin levels were considerably reduced and the patient became mildly diabetic but the main complication of treatment was a severe though reversible renal tubular defect. At necropsy considerable quantities of gastrin, but low levels of insulin and glucagon were extracted from a tumour metastasis.

Topics: Acetoacetates; Adenoma, Islet Cell; Antibiotics, Antineoplastic; Autopsy; Blood Glucose; Diabetes Insipidus; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Glucagon; Glucosamine; Humans; Insulin; Kidney Tubules; Lactates; Liver Neoplasms; Middle Aged; Mutagens; Neoplasm Metastasis; Nitroso Compounds; Nitrosourea Compounds; Peptic Ulcer Perforation; Pyruvates; Urea

Topics: Adenoma; Adenoma, Islet Cell; Adult; Calcium; Gastrectomy; Gastrins; Humans; Hyperparathyroidism; Male; Pancreatic Neoplasms; Parathyroid Glands; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Cross Reactions; Duodenal Ulcer; Fasting; Gastrins; Humans; Peptides; Pheochromocytoma; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Bile Acids and Salts; Dietary Fats; Enzyme Repression; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Jejunum; Lipase; Lipid Mobilization; Male; Middle Aged; Pancreas

The clinical data are presented of two women with profound metabolic upset from exceptional water and electrolyte losses in diarrhoea. One had an islet-cell adenoma of the pancreas and the other abnormal islets. Gastric and pancreatic function were abnormal in both, consistent with the subsequent demonstration of a pancreatic and choleretic secretagogue in the tumour tissue and pancreatic and gastric secretagogues in circulating blood (Cleator, Thomson, Sircus, and Coombes, 1970).

Topics: Adenoma, Islet Cell; Adult; Diarrhea; Female; Gastrins; Humans; Hypercalcemia; Hypokalemia; Hyponatremia; Islets of Langerhans; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Peptides; Radionuclide Imaging; Water-Electrolyte Balance

Methods for bio-assay of secretin-like humoral agents in both cat and dog are described. Bio-assay of tumour extracts and of plasma from patients with the pancreatic choleraic syndrome are described. The first patient was found to have choleretic and secretinlike activity in an extract of her pancreatic islet cell tumour and gastrin-like activity in her plasma. The second patient was found to have both secretin and gastrin-like activity in her plasma, as well as choleretic activity. It is concluded that at least part of the profuse, watery electrolyte diarrhoea of the ;pancreatic cholera' syndrome associated with peptide-secreting adenoma of the pancreas is likely to be a reflection of the excessive production of secretin, as well as of gastrin, and possibly also of a choleretic agent.

Topics: Adenoma, Islet Cell; Animals; Bicarbonates; Biological Assay; Cats; Diarrhea; Dogs; Gastrins; Humans; Pancreas; Pancreatic Neoplasms; Rats; Secretin; Water-Electrolyte Balance

Topics: Adenoma, Islet Cell; Diarrhea; Gastrins; Humans; Hypokalemia; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Autopsy; Biopsy; Cytoplasmic Granules; Gastric Mucosa; Gastrins; Glutamates; Histocytochemistry; Humans; Methods; Pancreas; Staining and Labeling; Swine; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Animals; Dogs; Female; Gastric Juice; Gastrins; Humans; Male; Pancreatic Neoplasms; Peptic Ulcer; Rats; Swine; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Angiography; Epinephrine; Female; Gastric Mucosa; Gastrins; Humans; Hydrochloric Acid; Melanocyte-Stimulating Hormones; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Adenoma, Islet Cell; Animals; Biological Transport, Active; Cell Membrane Permeability; Cholecystokinin; Diarrhea; Gallbladder; Gastrins; Gastrointestinal Hormones; Hypokalemia; Rabbits; Secretin; Tissue Extracts

Topics: Adenoma, Islet Cell; Animals; Biological Assay; Cricetinae; Gastrins; Histocytochemistry; Insulin; Insulin Secretion; Microscopy; Microscopy, Electron; Monoamine Oxidase; Neoplasm Transplantation; Secretin; Spectrophotometry

Topics: Adenoma; Adenoma, Islet Cell; Gastrins; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Microscopy, Electron; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Pancreas; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Antibiotics, Antineoplastic; Blood Glucose; Female; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hypoglycemia; Insulin; Insulin Secretion; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Radionuclide Imaging

Topics: Adenoma, Islet Cell; Adult; Carcinoid Tumor; Diagnosis, Differential; Duodenal Neoplasms; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Neoplasms; Peptic Ulcer; Postoperative Complications; Radiography; Serotonin; Tissue Extracts; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Calcium; Gastric Acidity Determination; Gastric Juice; Gastrins; Glucagon; Humans; Hypercalcemia; Insulin; Magnesium; Male; Pancreatic Neoplasms; Stimulation, Chemical; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenal Gland Diseases; Gastrins; Glucagon; Glucose Tolerance Test; Humans; Hypercalcemia; Hyperinsulinism; Immunoassay; Insulin; Insulin Antibodies; Insulin Secretion; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Parathyroid Diseases; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Aged; Biological Assay; Female; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hyperinsulinism; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Peptic Ulcer; Pituitary Neoplasms; Radiography; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Diarrhea; Duodenal Ulcer; Endoplasmic Reticulum; Gastrins; Humans; Hypokalemia; Liver; Microscopy, Electron; Neoplasm Metastasis

Topics: ACTH Syndrome, Ectopic; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Fatal Outcome; Female; Gastrins; Humans; Islets of Langerhans; Melanocyte-Stimulating Hormones; Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms

The production of ACTH-like material by tumours arising in non-endocrine tissue may initiate severe adrenocortical hyperfunction. The pathogenesis and clinical and laboratory features of Cushing's syndrome associated with such tumours are characteristic. The autonomous production by the tumour of ACTH-like material cannot be suppressed by exogenous corticoids. The onset of clinical symptoms is rapid; muscle wasting, general weakness, thirst and peripheral edema predominate, and the classical signs of Cushing's syndrome may be absent. High levels of plasma 17-hydroxycorticosteroids and urinary 17-hydroxycorticosteroids and 17-ketosteroids, usually with normal levels of urinary aldosterone, commonly occur. Hypokalemic alkalosis unresponsive to replacement therapy may cause death. In the case reported herein, the intriguing possibility exists that two hormone-like substances were produced by the primary growth and its metastases: one, ACTH-like, to account for the adrenal hyperplasia and Cushing's syndrome; and another, gastrin-like, giving rise to the ulcerogenic diathesis.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Islet Cell; Adrenalectomy; Adrenocortical Hyperfunction; Autopsy; Carcinoma, Islet Cell; Chloramphenicol; Cushing Syndrome; Drug Therapy; Gastrins; Humans; Hypokalemia; Neoplasm Metastasis; Neoplasms; Pancreatic Neoplasms; Pathology; Spironolactone; Zollinger-Ellison Syndrome

It is suggested that there are two hormonal syndromes associated with noninsulin-secreting islet cell tumours and this case is an example of the non-gastrin-secreting type with watery diarrhoea and hypokalaemia. The patient had histamine-fast achlorhydria and a normal gastric biopsy and no gastrin was recovered from the tumour tissue. The watery diarrhoea was isosmotic with plasma and was increased by an intravenous saline load. There was a dramatic response to steroids.

Topics: Achlorhydria; Adenoma, Islet Cell; Aldosterone; Cortisone; Dexamethasone; Diarrhea; Feces; Gastrins; Humans; Hypocalcemia; Hypokalemia; Neoplasms; Pancreatic Neoplasms; Potassium; Prednisone; Sodium; Surgical Procedures, Operative; Urine; Water-Electrolyte Balance; Zollinger-Ellison Syndrome

Topics: Adenoma; Adenoma, Islet Cell; Gastrins; Hormones; Humans; Neoplasm Metastasis; Neoplasms, Multiple Primary; Pancreas; Pancreatic Neoplasms; Peptic Ulcer

Topics: Adenoma, Islet Cell; Carcinoma, Islet Cell; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Stomach; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Neoplasms; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Black People; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Endocrine Glands; Endocrine System Diseases; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Peptic Ulcer; Ulcer

Topics: Adenoma, Islet Cell; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome