pituitrin and Pancreatic-Neoplasms

A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.

Topics: Adenoma, Islet Cell; APUD Cells; Apudoma; Cushing Syndrome; Endocrine System Diseases; Gastrointestinal Neoplasms; Hormones; Humans; Malignant Carcinoid Syndrome; Neoplasms, Nerve Tissue; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pheochromocytoma; Pituitary Neoplasms; Thyroid Neoplasms; Vasopressins; Zollinger-Ellison Syndrome

Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies.

Topics: Acute Disease; Adenoma, Islet Cell; Adult; Female; Gallium Radioisotopes; Hormones, Ectopic; Humans; Male; Middle Aged; Pancreatic Cyst; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Paraneoplastic Endocrine Syndromes; Radionuclide Imaging; Selenomethionine; Ultrasonography; Vasopressins; 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; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Alkalosis; Cushing Syndrome; Electrolytes; Endocrinology; Humans; Hypernatremia; Hypokalemia; Hyponatremia; Neoplasms; Pancreatic Neoplasms; Vasopressins; Water-Electrolyte Balance

Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity.. To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer.. Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal5-FU instillation 750-1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed.. The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4+/-2.5 and 6.1+/-5.4 mumol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment.. Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Female; Fluorouracil; Hemostatics; Humans; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Middle Aged; Palliative Care; Pancreatic Neoplasms; Survival Rate; Vasopressins

We report the case of a 68-year-old man, who presented in emergency care with inarticulate speech. The patient was diagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) associated with pancreatic cancer. All diagnostic criteria for SIADH were met, and cancer of the pancreatic tail was identified by computed tomography. Standard treatment for SIADH includes water restriction, oral NaCl, continuous intravenous infusion of 3% NaCl, and intravenous infusion of furosemide. However, these treatments have varying effectiveness and are difficult for both patients and medical staff. Furthermore, unless treatment of the underlying disease is successful, continued hospitalization is needed and the patient's quality of life is significantly impaired. In this case, hyponatremia improved with this standard treatment, but ascites and edema developed. We treated the patient with tolvaptan due to decreased cardiac function, and symptoms improved rapidly. Although surgery and chemotherapy could not be performed for pancreatic cancer, the SIADH was treated for 7 months without relapse. In summary, a case of SIADH complicated by pancreatic cancer was difficult to control with standard treatment, but responded rapidly to tolvaptan, and outpatient treatment could be continued for a long period. Tolvaptan is useful for the treatment of SIADH associated with cancer.

Topics: Aged; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Humans; Inappropriate ADH Syndrome; Male; Pancreatic Neoplasms; Quality of Life; Tolvaptan; Vasopressins

Functional pancreatic neuroendocrine tumors (pNETs) rarely produce vasopressin. Here, we reported a case of pNET producing vasopressin in a 78-year-old man with hyponatremia.. The patient presented with anorexia approximately 4 years ago, and the laboratory test results indicated hyponatremia. He was hospitalized 3 times subsequently due to anorexia in the past 4 years, during which laboratory tests consistently indicated severe hyponatremia.. Upon admission, his serum osmolarity, urine osmolarity, urine sodium level, and 24-hour urine sodium level was 277 mOsm/kg H2O, 465 mOsm/kg H2O, 82.5 mmol/L, and 140.25 mmol, respectively. Gallium-68-labeled tetraazacyclododecanetetraacetic acid-Dphel-Tyr3-octreotate positron emission tomography-computed tomography showed a high uptake lesion measuring approximately 1 cm in diameter in the pancreatic body, and the possibility of pNET was considered. Besides, laboratory tests showed that adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone released by the pituitary was insufficient in the case of low levels of cortisol, estradiol, progesterone, and testosterone. Thus, the diagnosis of the syndrome of inappropriate antidiuresis (SIAD) was considered along with hypopituitarism.. The patient underwent surgery, and pNET was confirmed by pathology examination. The immunohistochemical study showed that the tumor cells were positive for somatostatin receptors 2 and vasopressin.. In the last follow-up 17 months after surgery, the patient was in good condition, taking methylprednisolone 4 mg every other day, and had been free of anorexia or hyponatremia episodes.. This case illustrated the potential ectopic production of vasopressin resulting in SIAD in pNETs, highlighting the adoption of gallium-68-labeled tetraazacyclododecanetetraacetic acid-Dphel-Tyr3-octreotate positron emission tomography-computed tomography and vasopressin immunohistochemical staining in the evaluation of the etiology of SIAD.

Topics: Adrenal Cortex Hormones; Aged; Anorexia; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Neuroendocrine Tumors; Pancreatic Neoplasms; Vasopressins

The objective of the study is to report a rare case of pancreatic neuroendocrine tumor (pNET) producing insulin and vasopressin. We describe the clinical presentation and management of a metastatic pNET with refractory hypoglycemia and progressive severe hyponatremia. A 52-year-old patient had abdominal pain leading to the diagnosis of a tumor that was initially presumed to be splenic in origin. Investigations ultimately identified a pancreatic mass that on biopsy proved to be a pNET. Eventually, he developed extensive liver metastases, and with tumor progression, he manifested hypoglycemia and severe hyponatremia. He was managed with multiple therapies including somatostatin analogue, peptide-receptor-radionuclide-therapy (PRRT), diazoxide, and everolimus; none of these therapeutic modalities was successful in controlling functional and structural progression of the tumor. Ultimately, the pNET proved fatal and autopsy confirmed widely metastatic disease that stained strongly and diffusely for vasopressin, a feature not seen in the previous liver biopsy. This case illustrates the challenges of diagnosis and management of aggressive insulin-producing pNETs and highlights the potential concomitant ectopic production of vasopressin leading to refractory hyponatremia.

Topics: Humans; Inappropriate ADH Syndrome; Insulin; Male; Middle Aged; Neuroendocrine Tumors; Neurophysins; Pancreatic Neoplasms; Protein Precursors; Vasopressins

Vasoplegic syndrome is an unusual cause of refractory hypotension under general anesthesia. It is commonly described in the setting of cardiac surgery, but rarely seen in noncardiac setting. We describe successful management of vasoplegic syndrome during Whipple procedure with vasopressin infusion. A high index of suspicion and prompt treatment with vasopressin can be lifesaving in patients with risk factors for vasoplegic syndrome who present with severe refractory hypotension and who respond poorly to fluid administration and routine vasopressor infusion.

Topics: Aged; Anesthesia, General; Humans; Hypotension; Male; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Care; Vasoconstrictor Agents; Vasoplegia; Vasopressins

Multiple lines of evidence support the existence of crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling systems. However, the precise molecular mechanism(s) mediating this interaction is poorly understood. The results presented in this study show that exposure of ductal pancreatic adenocarcinoma BxPc-3, HPAF-II, and PANC-1 cells to insulin for as little as 1 min rapidly enhanced the magnitude and the rate of increase in intracellular Ca2+ concentration produced by the GPCR agonists bradykinin, angiotensin II, vasopressin, neurotensin, and bombesin. The potentiating effect of insulin was dose dependent, and it was produced in response to Gq protein-coupled, but not Gi protein-coupled, receptor agonists. Real-time imaging of single cells showed that treatment with insulin enhances the rate and magnitude of phosphatidylinositol 4,5-bisphosphate hydrolysis and generation of inositol 1,4,5-trisphosphate in response to GPCR stimulation. Short-term treatment with rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, completely abrogated the ability of insulin to increase the rate and magnitude of Ca2+ signaling and production of inositol 1,4,5-trisphosphate in response to bradykinin stimulation, indicating that insulin potentiates Gq protein-coupled receptor signaling through an mTOR-dependent pathway. We propose that the potentiation of GPCR signaling by insulin provides a mechanism by which insulin enhances cellular responsiveness to Gq protein-coupled receptor agonists, including GPCR-mediated autocrine and paracrine loops in cancer cells.

Topics: Angiotensin II; Blotting, Western; Bombesin; Bradykinin; Calcium Signaling; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Hydrolysis; Inositol 1,4,5-Trisphosphate; Insulin; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Microscopy, Fluorescence; Myristoylated Alanine-Rich C Kinase Substrate; Neurotensin; Pancreatic Neoplasms; Phosphatidylinositol 4,5-Diphosphate; Phosphorylation; Protein Kinases; Receptors, G-Protein-Coupled; Sirolimus; TOR Serine-Threonine Kinases; Vasopressins

Topics: Abdomen, Acute; Adult; Aged; Hemostatics; Humans; Liver Diseases; Male; Middle Aged; Multiple Trauma; Pancreatic Neoplasms; Pancreaticoduodenectomy; Rupture, Spontaneous; Vasopressins; Water-Electrolyte Imbalance

We describe a 73-year old man with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) due to an ectopic ADH-producing pancreatic adenocarcinoma. His laboratory findings showed marked hyponatremia, and the water load test showed uncontrolled ADH secretion. The imaging studies revealed pancreatic body cancer. Histological examination revealed an adenocarcinoma of the pancreas, which was positive for ADH immuno-staining. The ADH in the tumor extract was 53.3 pg/g wet weight. In attempt to diagnose ADH-production from the tumor, the ADH in his pancreatic juice was measured and found to be 2.1 pg/ml. We conclude that it is valid to measure the ADH in pancreatic juice to diagnose ectopic ADH production by tumors.

Topics: Adenocarcinoma; Aged; Hormones, Ectopic; Humans; Inappropriate ADH Syndrome; Male; Pancreatic Juice; Pancreatic Neoplasms; Vasopressins

The effect of vasopressin on voltage-sensitive Ca2+ currents in the rat insulinoma cell line RINm5F has been investigated in patch-clamp whole-cell and single-channel current recording experiments. In the whole-cell recording configuration the dominant inward current in the presence of tetrodotoxin was noninactivating and had a high voltage threshold. This current was much enhanced when external Ca2+ was replaced by Ba2+ and was blocked by 1 microM nifedipine. It can therefore be classified as an L-current. Vasopressin enhanced the L-current without changing the voltage threshold of activation or the voltage at which the peak current was observed. Vasopressin effects were seen at concentrations as low as 0.01 nM, and the maximal effect was observed at about 1 nM. In higher concentrations the vasopressin effects were weaker, with effects at 50 nM of about the same magnitude as at 0.01 nM. In single-channel current recording experiments carried out with the cell-attached configuration there were no effects on single L-channel currents when vasopressin was added to the bath solution, but in experiments in which vasopressin (5 nM) was infused into the patch pipette a marked increase in the apparent channel open state probability was observed. We conclude that vasopressin, a peptide that is known to markedly enhance glucose-evoked insulin secretion, stimulates opening of the voltage-sensitive Ca2+ channels in insulin-secreting cells.

Topics: Animals; Barium; Biological Transport; Calcium; Calcium Channels; Dose-Response Relationship, Drug; Electric Conductivity; Electric Stimulation; Insulinoma; Nifedipine; Pancreatic Neoplasms; Rats; Tumor Cells, Cultured; Vasopressins

The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.

Topics: Adrenocorticotropic Hormone; Apudoma; Diagnosis, Differential; Hormones, Ectopic; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Melanocyte-Stimulating Hormones; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Radioimmunoassay; Vasopressins

Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Choriocarcinoma; Culture Media; Diuresis; Female; In Vitro Techniques; Liver; Liver Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Oxytocin; Pancreatic Neoplasms; Pregnancy; Rats; Recurrence; Uterine Neoplasms; Vasopressins

Topics: Animals; Bethanechol Compounds; Cholecystokinin; Female; Glucagon; Humans; Pancreatic Cyst; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Propantheline; Radioisotopes; Radionuclide Imaging; Rats; Selenium; Stomach Ulcer; Vasopressins

Topics: Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Erythropoietin; Gonadotropins, Pituitary; Growth Hormone; Humans; Insulin; Insulin Secretion; Liver Neoplasms; Lung Neoplasms; Malignant Carcinoid Syndrome; Melanocyte-Stimulating Hormones; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Prolactin; Serotonin; Thymus Neoplasms; Vasopressins

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenocorticotropic Hormone; Amino Acids; Animals; Biological Assay; Carcinoma, Bronchogenic; Corticotropin-Releasing Hormone; Dexamethasone; Electrophoresis; Feedback; Hormones, Ectopic; Humans; Lung Neoplasms; Lysine; Metyrapone; Neoplasm Metastasis; Neoplasm Proteins; Pancreatic Neoplasms; Peptides; Rats; Vasopressins

Topics: Adult; Aged; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Pituitary Neoplasms; Polyuria; Vasopressins

Topics: Animals; Dogs; Electrolytes; Hormones, Ectopic; Humans; Hyponatremia; Lung Neoplasms; Lymphoma; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Vasopressins

Topics: Adenocarcinoma; Animals; Biological Assay; Carcinoma, Bronchogenic; Chickens; Humans; Hyponatremia; Lung Neoplasms; Male; Methods; Middle Aged; Neoplasm Metastasis; Neoplasms, Multiple Primary; Osmolar Concentration; Oxytocin; Pancreatic Neoplasms; Pneumonectomy; Rabbits; Radioimmunoassay; Rats; Vasopressins

Topics: Animals; Anura; Biological Assay; Carcinoma, Bronchogenic; Chromatography, Gel; Chromatography, Ion Exchange; Chymotrypsin; Diuresis; Hormones, Ectopic; Humans; Hyponatremia; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Metastasis; Pancreatic Neoplasms; Thioglycolates; Trypsin; Vasopressins

Topics: Aged; Animals; Anura; Bronchial Neoplasms; Carcinoma; Humans; Hyponatremia; Hypopituitarism; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Permeability; Sodium; Urinary Bladder; Vasopressins; Water