c-peptide and Liver-Neoplasms

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Autoimmune Diseases; C-Peptide; Dexamethasone; Diazoxide; Diet, Diabetic; Female; Glucose; Glucose Intolerance; Humans; Hyperinsulinism; Hypoglycemia; Immunosuppressive Agents; Insulin; Liver Neoplasms; Polyethylene Glycols; Proinsulin; Sigmoid Neoplasms

About 8%-15% of the patients with organic hyperinsulinism have an islet cell carcinoma (13% in our series). In addition to a history of complaints of relatively recent onset, the patients present clinically the typical intermittent neurologic-psychiatric symptoms concurrently associated with hypoglycemia. The diagnosis is established biochemically on the basis of hypoglycemia, with inadequate incrementation of the insulin concentration subsequent to suppression and provocation tests. Elevated serum proinsulin and, in most patients, an increased insulin secretion rate are usually found after administration of agents such as glucose or leucine. Localization of the tumors is achieved by selective coeliacography as well as abdominal computerized axial tomography. The islet cell carcinoma is found most frequently in the tail of the pancreas, less frequently in the body and head of the pancreas. Metastatic spread is seen early into adjacent lymph nodes and especially in the liver. The treatment of choice is surgical resection of the tumor. Even in cases with advanced metastatic involvement, surgical intervention appears indicated. Medical treatment includes the administration of diazoxide, long-acting glucagon as well as the cytostatic agent streptozotocin. The average survival time is 30-40 months after diagnosis (in our series 79 months). Thus, the prognosis of patients with islet cell carcinoma appears relatively favorable, especially when compared with adenocarcinoma of the pancreas.

Topics: Adenoma; Adenoma, Islet Cell; C-Peptide; Diagnosis, Differential; Diazoxide; Female; Glucagon; Humans; Hyperinsulinism; Liver Neoplasms; Lymphatic Metastasis; Male; Pancreatic Neoplasms; Prognosis; Proinsulin; Streptozocin

Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A

Topics: C-Peptide; Cohort Studies; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hemoglobin A; Humans; Liver Neoplasms; Male

The aim of the study was to address the origin and natural history of malignant insulinoma.. Retrospective review of medical records of patients diagnosed with insulinoma at Cedars-Sinai Medical Center between 2000 and 2015 was conducted. Hormonal expression in tumor specimens was examined by immunostaining.. All the 9 patients with malignant insulinoma (35% of 26 patients with insulinoma) already had liver metastasis at hypoglycemia presentation with bulky cumulative tumor burden. Six patients had de novo diagnosis, 2 had known metastatic nonfunctioning pancreatic neuroendocrine tumor, and 1 had a known pancreatic mass. Tumor grade at presentation was G1 in 4 patients, G2 in 4, and unknown in 1. Four patients died 2 to 32 months after presentation, all with extensive liver tumor involvement. Tumor expression of proinsulin and insulin was heterogeneous and overall infrequent. The proinsulin levels and proinsulin/insulin molar ratio in patients with malignant versus benign insulinoma were 334 versus 44 pmol/L and 2.1 versus 0.9, respectively.. Malignant insulinoma seems to arise from and behave like nonfunctioning pancreatic neuroendocrine tumor oncologically but with metachronous hyperinsulinemic hypoglycemia. High proinsulin levels and proinsulin/insulin molar ratio may suggest malignant insulinoma.

Topics: Adult; Aged; C-Peptide; Female; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulinoma; Liver Neoplasms; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Proinsulin; Retrospective Studies

Most cases of insulinomas are benign. We report a case of a malignant form of insulinoma. A 46-year-old man presented with behavioural changes associated with hypoglycaemia. Diagnostic work up revealed high serum insulin, high C-peptide and low glucose levels, compatible with endogenous hyperinsulinaemic hypoglycaemia. CT imaging of the abdomen revealed a pancreatic head mass and multiple liver masses. Biopsy of the pancreatic mass revealed a grade three pancreatic neuroendocrine carcinoma. Histological analysis of a liver mass showed that it was identical to the pancreatic mass, confirming its metastatic nature. The patient underwent distal pancreatectomy with en bloc splenectomy. There was persistence of hypoglycaemic symptoms after removal of the pancreatic mass, suggesting that the liver metastases were also functioning. Symptoms were controlled by diazoxide and octreotide long-acting release. The patient is already 1 year postsurgery with no recurrence of severe hypoglycaemia, and he has good functional capacity and has returned to his office job.

Topics: Biopsy; Blood Glucose; C-Peptide; Carcinoma, Neuroendocrine; Diazoxide; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Secretion; Insulinoma; Liver Neoplasms; Male; Middle Aged; Octreotide; Pancreas; Pancreatectomy; Pancreatic Neoplasms

A 67 year old female patient was admitted to our clinic with recurrent hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin, and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the spleen with metastases of the liver, expressing somatostatin receptors. Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma. Since the hypoglycemias could not sufficiently be controlled by subcutaneous administration of octreotide and by oral glucose intake, surgical debulking was performed in a palliative intention. After resection the patient was free of hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine neoplasia) should be considered. Excision of the tumor is recommended in patients with benign solitary insulinomas. If complete excision is impossible, there are several therapeutic options that aim at preventing hypoglycemia. Thus, in contrast to other extended tumors, surgery is reasonable in malignant insulinoma even in case of metastatic disease.

Topics: Aged; Blood Glucose; C-Peptide; Chromogranin A; Diagnosis, Differential; Disease Progression; Female; Humans; Hypoglycemia; Insulin; Insulinoma; Liver Neoplasms; Magnetic Resonance Imaging; Palliative Care; Pancreatic Neoplasms; Recurrence; Ultrasonography

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Topics: Adult; C-Peptide; Diseases in Twins; Growth Hormone; Hemangioendothelioma; Hepatocytes; Humans; Immunosuppressive Agents; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Interleukin-6; Kinetics; Liver; Liver Neoplasms; Liver Regeneration; Liver Transplantation; Living Donors; Male; Models, Statistical; Somatomedins; Time Factors; Transplantation, Isogeneic; Tumor Necrosis Factor-alpha; Twins, Monozygotic

Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the beta-cell function and an insulin clamp combined with [3-(3)H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (P <.05) and insulin deficiency during the OGTT (P <.05). Liver transplantation normalized endogenous glucose production and insulin sensitivity but failed to cure diabetes in 8 of the 24 patients because a markedly low insulin response during the OGTT. Age, body mass index, family history of diabetes, immunosuppressive drugs, and pathogenesis of cirrhosis did not predict in whom liver transplant was going to cure diabetes. On the contrary, a reduced secretory response characterized the patients in whom the transplant would not be curative. In summary, insulin resistance was a primary event complicating cirrhosis but additional beta-cell secretory defects were crucial for development of diabetes. Liver transplantation, lessening insulin resistance, cured hepatogenous diabetes in 67% of cirrhotic-diabetic patients; nevertheless 33% were still diabetics because the persistence of a reduced beta-cell function, which makes these patients eventually eligible for combined islet transplantation.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Carcinoma, Hepatocellular; Diabetes Complications; Diabetes Mellitus; Follow-Up Studies; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Middle Aged

Following a hyperosmolar diabetic coma in a cirrhotic patient with hepatocellular carcinoma undergoing transcatheter arterial chemo-embolization, we assessed the prevalence, severity, causes and prognostic impact of impaired glucose metabolism following transcatheter arterial chemo-embolization.. Plasma glucose, pancreatic and thyroid hormones, cortisol, growth hormone, ACTH and TSH concentrations were determined before and after transcatheter arterial chemo-embolization in 98 patients (70 with a normal fasting glucose, 7 with mild fasting hyperglycaemia and 21 diabetics) undergoing 226 transcatheter arterial chemo-embolization procedures. Child status, body temperature, serum ALT and amylase levels, tumour size, gelfoam embolization and disease aetiology were recorded. Liver function was assessed before and after transcatheter arterial chemo-embolization by measuring monoethylglycinexylidide formation after i.v. lidocaine.. A significant rise in glucose levels (p < 0.0001) was observed in 30/98 patients. Hyperglycaemia was more frequent in diabetics (67%) and patients with mild fasting hyperglycaemia (71%). Glucose concentrations doubled in 12 patients; 4 required long-term insulin. Fever, a previously altered carbohydrate metabolism and raised ALT levels were prognostic factors for hyperglycaemia (p < 0.01). Plasma C-peptide, glucose/insulin and glucose/C-peptide ratios, were increased after transcatheter arterial chemo-embolization (p < 0.05). Transcatheter arterial chemo-embolization was followed by a reduction in the monoethylglycinexylidide formation capacity (p < 0.05), particularly in hyperglycaemia patients (p < 0.02).. Transcatheter arterial chemo-embolization is frequently followed by a derangement in glucose metabolism which is potentially severe, associated with preceding glucose imbalance, fever and a transient deterioration in liver function.

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Fasting; Female; Hormones; Humans; Hyperglycemia; Insulin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

Topics: Adolescent; C-Peptide; Carcinoma, Hepatocellular; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans Transplantation; Liver Neoplasms; Liver Transplantation; Pancreatectomy; Time Factors

Proinsulin is usually targetted to the regulated secretory pathway of beta cells, and converted to insulin in beta granules. Under certain pathological situations, a significant amount of proinsulin becomes diverted to the constitutive pathway. To study the kinetics of proinsulin conversion in the constitutive pathway, FAO (hepatoma) cells, which secrete proteins uniquely via this pathway and not the regulated pathway, were stably transfected with cDNA encoding human, rat I or rat II proinsulin. Products released to the medium of transfected cells were analysed by reversed phase HPLC and radioimmunoassay. For human proinsulin, des 31,32 split proinsulin (the conversion intermediate resulting from cleavage only at the B-chain/C-peptide junction followed by trimming of C-terminal basic residues by carboxypeptidase) was the only detectable conversion intermediate; for rat proinsulin II it was des 64,65 split proinsulin (cleaved and trimmed only at the C-peptide/A-chain junction); for rat proinsulin I, both intermediates were seen. Complete processing to insulin occurred for all three, but was most extensive for rat proinsulin I. When considered with the corresponding proinsulin sequences, these data show that a -4 basic residue (i.e. 4 residues N-terminal to the site of cleavage) facilitates proinsulin conversion in the constitutive pathway, and that arginine is preferred over lysine.

Topics: Amino Acid Sequence; Animals; C-Peptide; Carcinoma, Hepatocellular; Cell Line; DNA, Complementary; Humans; Insulin; Kinetics; Liver Neoplasms; Macromolecular Substances; Molecular Sequence Data; Proinsulin; Protein Processing, Post-Translational; Rats; Substrate Specificity; Transfection; Tumor Cells, Cultured

Furin is a mammalian propeptide-processing endoprotease in nonendocrine cells and has been demonstrated to be present in virtually all nonendocrine cells, including fibroblasts, epithelial cells, and hepatocytes. Furin cleaves the concensus processing site -Arg-4-X-3-Lys/Arg-2-Arg-1 decreases X+1-. Some subunit-containing precursor proteins, including an insulin receptor precursor, possess an additional basic residue at position -3, thus forming a tetrabasic processing site. This implies that a tetrabasic processing site must be easily cleavable in nonendocrine cells. We created a mutant proinsulin DNA with a peptide structure comprised of B- and A-chains linked to the C-peptide by a pair of tetrabasic residues, in the following order: B-chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys-Arg-A-chain. The native proinsulin structure was B-chain-Arg-Arg-C-peptide-Lys-Arg-A-chain. Both the native and mutant proinsulins were expressed in the following four cell lines: a monkey kidney-derived cell line (COS-7), a Chinese hamster ovary-derived cell line (CHO), a human liver cancer-derived cell line (HepG2), and a mouse fibroblast-like cell line (NIH3T3). We used these cell lines because they contain different quantities of furin mRNA, ranking as follows: NIH3T3 > HepG2 > COS > CHO. When mutant insulin was expressed in these cells, the conversion of proinsulin to mature insulin was approximately 85% in NIH3T3, 70% in HepG2, 60% in COS, and 50% in CHO. The conversion correlated well with the furin expression in each cell line as measured by the density of its Northern blot band. Moreover, in CHO, the cell line with the lowest furin expression, coexpression of mutant proinsulin with furin resulted in complete conversion of proinsulin to mature insulin.

Topics: 3T3 Cells; Amino Acid Sequence; Animals; C-Peptide; Cell Line; Chlorocebus aethiops; CHO Cells; Cricetinae; Furin; Gene Expression; Humans; Insulin; Kidney; Liver Neoplasms; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Proinsulin; Subtilisins; Transfection; Tumor Cells, Cultured

Intermittent hepatic dearterialisation is used in palliation of liver malignancy. In rats hepatic dearterialisation is accompanied by glucose intolerance and impaired insulin secretion, but it is not known if similar effects occur in man. Six patients with nonresectable liver malignancy were subjected to an intravenous glucose (50 g) challenge before dearterialisation (control challenge), during a 1-hour dearterialisation period, and in the immediate reperfusion phase after the end of 1-hour dearterialisation. Insulin secretion, as judged by the plasma levels of both insulin and C peptide, was inhibited during the 1-hour dearterialisation, while the glucose elimination rate was delayed (both p less than 0.03). Contrastingly, in the immediate reperfusion phase both insulin secretion and glucose elimination did not differ from values after the control challenge. We therefore conclude that hepatic dearterialisation in patients with liver malignancy is accompanied by inhibited insulin secretion and glucose intolerance, both readily reversible.

Topics: Aged; Blood Glucose; C-Peptide; Constriction; Female; Hepatic Artery; Humans; Insulin; Liver Neoplasms; Male; Middle Aged

We previously found that patients with hypoglycemia due to chronic renal and liver disease had anomalous metabolic responses to glucose and glucagon stimulation. In this study we evaluated the use of glucagon (2 mg, iv) tests in the diagnosis of spontaneous hypoglycemia secondary to hepatocellular carcinoma (HCC) and insulinoma. Twenty-one normal subjects, 45 patients with HCC (11 with hypoglycemia), and 14 patients with insulinoma (all with hypoglycemia) were studied. The fasting blood glucose level was low in all patients with hypoglycemia. The fasting plasma insulin and C-peptide concentrations were high in patients with insulinoma and low in patients with HCC and hypoglycemia. The blood glucose responses to glucagon administration were less than normal in patients with HCC and hypoglycemia and within normal limits in patients with insulinoma. The insulinoma patients had increased plasma insulin and C-peptide responses to glucagon despite having low blood glucose levels. Compared with the HCC patients without hypoglycemia, HCC patients with hypoglycemia had impaired plasma insulin and C-peptide responses. The fasting hypoglycemia, hypoinsulinemia, and impaired insulin/C-peptide responses to glucagon in patients with hepatoma and hypoglycemia presumably reflect the production of insulin-like substances by the hepatoma. We conclude that glucagon administration results in characteristic responses in these groups of patients and can be of use in the diagnosis of spontaneous hypoglycemia secondary to hepatoma or insulinoma.

Topics: Adenoma, Islet Cell; Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Carcinoma, Hepatocellular; Female; Glucagon; Humans; Hypoglycemia; Insulin; Insulinoma; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms

Fourteen normal controls, eleven patients with non-alcoholic cirrhosis, twenty-nine with hepatocellular carcinoma (HCC) and six with HCC and hypoglycemia were studied. The tests performed include iv glucose tolerance test (25 g) and glucagon challenge test (2 mg). In cirrhosis, glucose intolerance and insulin resistance were demonstrated. The fasting hyperinsulinemia in cirrhosis is the result of decreased degradation as shown by the normal fasting C-peptide. The increased insulin responses to glucose, despite a normal C-peptide response, further supports the importance of impaired degradation in the pathogenesis of hyperinsulinemia after challenge. Despite a strong etiological association between cirrhosis and HCC, patients with HCC do not have significant hyperinsulinemia or glucose intolerance. This provides metabolic evidence to support the clinico-pathological observation that HCC occurred when cirrhosis was not advanced or in a precirrhotic stage. In HCC patients with clinically overt hypoglycemia, the fasting glucose, insulin and C-peptide were very low. The C-peptide responses to glucose and glucagon challenges were suppressed despite pharmacologic stimulation. This can be explained by the suppression of insulin secretion by a circulating substance secreted by hepatoma. The results support the pathogenetic importance of insulin-like activities recently detected in HCC patients with hypoglycemia.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Carcinoma, Hepatocellular; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

A woman with a multiple-hormone-producing pancreatic islet cell tumor with hepatic metastases and with recurrent hypoglycemic attacks, was treated with streptozotocin. After this treatment, the elevated serum levels of insulin, C-peptide, glucagon and serotonin fell markedly and the low level of fasting blood glucose returned to normal. In accordance with these hormonal changes, scintiscan and CT scan revealed marked regression of the metastatic tumors in the liver. She is alive at this writing, five years after the streptozotocin treatment. Streptozotocin should thus be considered for treatment of malignant islet cell carcinoma with liver metastases and which is not amenable to surgery.

Topics: Adenoma, Islet Cell; Blood Glucose; C-Peptide; Female; Glucagon; Humans; Insulin; Insulinoma; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms; Serotonin; Streptozocin

One hundred consecutive patients with nonautoimmune chronic active hepatitis (51% HBsAg-positive), 50 patients with cirrhosis (38% HBsAg-positive), 25 patients with chronic persistent hepatitis, and 118 patients with hepatoma who were seen at this hospital were reviewed to determine the prevalence and characteristics of glucose intolerance and diabetes in these conditions. Diabetes (fasting serum glucose greater than 7.8 mmol/L, 140 mg/dl on two separate occasions) was present in 8% of patients with chronic persistent hepatitis and mild chronic active hepatitis, 44% of patients with severe chronic active hepatitis, 40% of patients with cirrhosis, and 15% of patients with hepatoma, compared with 7% of all other patients aged 35 yr or over, undergoing liver biopsy. Compared with this high prevalence of diabetes in liver disease, only 3% of diabetic patients referred to the hospital diabetic clinic had chronic hepatitis or cirrhosis. Glucose tolerance was similar in chronic active hepatitis and cirrhosis and was characterized initially by basal hyperinsulinemia, normal basal glucose levels but elevated serum glucose following glucose loading, and evidence of insulin resistance. We suggest that the high prevalence of diabetes in chronic active hepatitis and cirrhosis in Saudi Arabia is due to the insulin resistance of chronic liver disease acting over many years in a population with a high genetic predisposition to diabetes.

Topics: Adrenal Cortex Hormones; C-Peptide; Carcinoma, Hepatocellular; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Infant; Insulin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

The influence of two sulfonylureas on blood glucose and plasma immunoreactive insulin (IRI) and C-peptide responses to a standardized meal was investigated in a patient with type 2 diabetes and a liver disease with enhanced peripheral levels of liver enzymes. The very high fasting values of plasma IRI and C-peptide were further elevated by the meal. This response to the meal was markedly enhanced by both sulfonylureas, glipizide and glibenclamide. The blood glucose increment after the meal was diminished by sulfonylureas. Sulfonylureas thus seem to have beneficial effects in this diabetic patient, who had a liver disease and markedly elevated basal levels of plasma IRI and C-peptide concentrations.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Food; Glipizide; Glyburide; Humans; Insulin; Liver Diseases; Liver Neoplasms; Sulfonylurea Compounds

A case of somatostatinoma syndrome in a 30-year-old woman is presented. Basal levels of growth hormone and of pancreatic and gastric hormones were reduced and the response of growth hormone, insulin and C-peptide to stimuli such as arginine, glucose, glibenclamide and calcium was virtually abolished. Similarly, gastric acid secretion, pancreatic exocrine function and intestinal absorption were significantly reduced. On the other hand, basal and stimulated levels of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were within the normal range. Plasma somatostatin-like immunoreactivity was increased to 600-2,000 pg/ml (normal: 88-140 pg/ml). Immunocytochemical studies demonstrated the presence of somatostatin immunoreactive material in the primary tumour in the head of the pancreas and in the liver metastases. In spite of two courses of chemotherapy with streptozotocin and 5-fluorouracil the patient died due to liver failure 5 months after the first admission to hospital.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Humans; Insulin; Liver Neoplasms; Pancreatic Neoplasms; Pancreatic Polypeptide; Pituitary Hormones; Somatostatin; Somatostatinoma; Streptozocin; Xylose

The results of clinical endocrine and metabolic studies on a 57-year-old female with surgically and autopsy verified glucagonoma syndrome were presented. All of the clinical manifestations of glucagonoma syndrome so far reported in the literature were noted but there was no evidence indicating the presence of multiple endocrine adenomatosis. The plasma IRG level was always more than 20 times above the normal, and the IRG response to insulin and tolbutamide injection was abnormal and the results of the other endocrinological studies revealed less remarkable features, if any. The surgically removed metastatic tumor of the liver contained an enormous amount of IRG and an appreciable amount of IRI, indicating that the elevated plasma IRG was mainly of tumor origin. These results clearly indicate that in glucagonoma there is some abnormality in glucagon release from the tumor. In addition to these findings, hypocalcemia, cardiac left ventricular hypertrophy and gastrointestinal dysfunction reportedly due to hyperglucagonemia were also seen in this patient.

Topics: Adenoma, Islet Cell; C-Peptide; Endocrine Glands; Female; Glucagon; Glucagonoma; Glucose Tolerance Test; Humans; Insulin; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms; Tolbutamide

Key enzymes of gluconeogenesis in the liver, phosphoenolpyruvate carboxykinase [EC 4.1.1.32] and glucose-6-phosphatase [EC 3.1.3.9], were studied in patients with primary or metastatic hepatic cancer. Liver specimens for enzyme assay were obtained by necropsy performed within four hours after death. It was confirmed that both enzyme activities in rat liver preserved at 4 degrees C remained unchanged within nine hours after the removal of the tissue. Activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase decreased to below ten per cent of the control in neoplastic liver tissue of patients with hepatocellular carcinoma accompanied with liver cirrhosis. These two enzyme activities in cirrhotic tissue of patients with hepatocellular carcinoma were lower than those in patients merely with cirrhosis. In patients with metastatic hepatic cancer both two enzyme activities further decreased and were scarcely detected not only in neoplastic tissue but also in non-neoplastic tissue. These results show that hepatic gluconeogenesis markedly decreases in patients with primary or metastatic hepatic cancer. The biochemical analysis of the blood in hepatic cancer, decreased in blood glucose and release in immunoreactive glucagon, also suggested the suppression of gluconeogenesis.

Topics: Adult; Aged; Animals; Blood Glucose; C-Peptide; Carcinoma, Hepatocellular; Female; Glucagon; Gluconeogenesis; Glucose-6-Phosphatase; Humans; Insulin; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Phosphoenolpyruvate Carboxykinase (GTP); Rats

Topics: Adenoma, Islet Cell; Arginine; Blood Glucose; C-Peptide; Glucagon; Glucose Tolerance Test; Humans; Insulin; Liver Neoplasms; Male; Middle Aged; Somatostatin; Streptozocin

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.

Topics: C-Peptide; Celiac Disease; Cholelithiasis; Diabetes Complications; Glucagon; Hormones, Ectopic; Humans; Hypothalamus; Islets of Langerhans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Pituitary Gland; Radioimmunoassay; Somatostatin; Syndrome