Pancreatic Venous Sampling Research Articles

Clinical and histological heterogeneity of congenital hyperinsulinism due to paternally inherited heterozygous ABCC8/KCNJ11 mutations.

Congenital hyperinsulinism (CHI) has two main histological types: diffuse and focal. Heterozygous paternally inherited ABCC8/KCNJ11 mutations (depending upon whether recessive or dominant acting and occurrence of somatic maternal allele loss) can give rise to either phenotype. However, the relative proportion of these two phenotypes in a large cohort of CHI patients due to paternally inherited heterozygous ABCC8/KCNJ11 mutations has not been reported. The purpose of this study is to highlight the variable clinical phenotype and to characterise the distribution of diffuse and focal disease in a large cohort of CHI patients due to paternally inherited heterozygous ABCC8/KCNJ11 mutations. A retrospective chart review of the CHI patients due to heterozygous paternally inherited ABCC8/KCNJ11 mutations from 2000 to 2013 was conducted. Paternally inherited heterozygous ABCC8/KCNJ11 mutations were identified in 53 CHI patients. Of these, 18 (34%) either responded to diazoxide or resolved spontaneously. Fluorine-18 l-3, 4-dihydroxyphenylalanine positron emission tomography computerised tomography 18F DOPA-PET CT) scanning in 3/18 children showed diffuse disease. The remaining 35 (66%) diazoxide-unresponsive children either had pancreatic venous sampling (n=8) or 18F DOPA-PET CT (n=27). Diffuse, indeterminate and focal disease was identified in 13, 1 and 21 patients respectively. Two patients with suspected diffuse disease were identified to have focal disease on histology. Paternally inherited heterozygous ABCC8/KCNJ11 mutations can manifest as a wide spectrum of CHI with variable 18F DOPA-PET CT/histological findings and clinical outcomes. Focal disease was histologically confirmed in 24/53 (45%) of CHI patients with paternally inherited heterozygous ABCC8/KCNJ11 mutations.

The Value of Radiologic Interventions and 18F-DOPA PET in Diagnosing and Localizing Focal Congenital Hyperinsulinism: Systematic Review and Meta-Analysis

PurposeThis systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and 18F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI).ProceduresThis systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR).Results 18F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy.ConclusionsThis systematic review and meta-analysis found evidence for the superiority of 18F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.

Familial Focal Congenital Hyperinsulinism

Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia. Histologically, there are two subgroups, diffuse and focal. Focal CHI is a consequence of two independent events, inheritance of a paternal mutation in ABCC8/KCNJ11 and paternal uniparental isodisomy of chromosome 11p15 within the embryonic pancreas, leading to an imbalance in the expression of imprinted genes. The probability of both events occurring within siblings is rare. We describe the first familial form of focal CHI in two siblings. The proband presented with medically unresponsive CHI. He underwent pancreatic venous sampling and Fluorine-18-L-dihydroxyphenylalanine positron emission tomography scan, which localized a 5-mm focal lesion in the isthmus of the pancreas. The sibling presented 8 yr later also with medically unresponsive CHI. An Fluorine-18-L-dihydroxyphenylalanine positron emission-computerised tomography scan showed a 7-mm focal lesion in the posterior section of the head of the pancreas. Both siblings were found to be heterozygous for two paternally inherited ABCC8 mutations, A355T and R1494W. Surgical removal of the focal lesions in both siblings cured the Hyperinsulinaemic hypoglycaemia. This is the first report of focal CHI occurring in siblings. Genetic counseling for families of patients with focal CHI should be recommended, despite the rare risk of recurrence of this disease.

Value of18F–fluoro-l-dopa PET in the Preoperative Localization of Focal Lesions in Congenital Hyperinsulinism

To retrospectively compare fluorine 18 ((18)F) fluoro-L-dopa positron emission tomography (PET) and pancreatic venous sampling (PVS) in the preoperative differentiation of diffuse from focal congenital hyperinsulinism (CHI) and localization of focal lesions. This study was approved by the institutional ethical committee, and informed consent for the research study was obtained from the parents of all subjects. Fifty-one patients evaluated for focal CHI between January 1, 1995, and January 31, 2008, were included. Thirty five underwent PVS evaluation alone, and 16 underwent a PET evaluation alone. The sensitivity values of each technique for the diagnosis and localization of focal lesions were compared in regard to results of surgery and pathologic analyses. In each patient, perioperative treatment was reviewed, and the presence of postoperative hypoglycemia was assessed as evidence of incomplete resection. Comparisons of the sensitivity values and recurrence rates were performed by using the Fisher exact test in regard to the number of patients. Comparisons of median age, weight, or number of biopsies were performed with a two-tailed unpaired Mann-Whitney U test. A difference with P < .05 was considered significant. For PVS and PET groups, there was no error in differentiating focal from diffuse forms. PVS was not completed in four of 35 patients. In 27 (87%) of 31 patients in whom PVS was completed and 13 (81%) of 16 patients in whom PET was completed, preoperative localization of the focal lesion was in accordance with the surgical findings (P = .7). Although not significant, the number of biopsies performed before discovering the focal lesion was higher in the PET group compared with the PVS group (P = .06). Inadequate localization occurred in two (6%) patients in the PVS group and five (31%) patients in the PET group at initial preoperative imaging study; these patients underwent repeat surgery for residual CHI (P = .03). (18)F-fluoro-L-dopa PET is equivalent to PVS in the characterization of CHI but does not provide localization of the lesion as precisely as does PVS.

18F]Fluoro-L-DOPA PET/CT in Congenital Hyperinsulinism

Congenital hyperinsulinism can be divided into diffuse or focal form. The treatment and outcome depend on distinguishing between the 2 forms. Pancreatic venous sampling was the only method available to localize the insulin secretion. [F]Fluoro-levodopa, 3,4-dihydroxy-L-phenylalanine positron emission tomography/computed tomography is a noninvasive imaging investigation and increasingly used to determine the type of hyperinsulinism preoperatively. We present a case of diffuse form of congenital hyperinsulinism demonstrated by the [F]levodopa, 3,4-dihydroxy-L-phenylalanine positron emission tomography/computed tomography preoperatively and review the literature.

Simultaneous Presentation of an Insulinoma and Type 2 Diabetes Mellitus

Hypoglycemia in the setting of diabetes mellitus is usually ascribed to the management of diabetes mellitus. Rarely, an additional etiology should be considered. We report a 35-year-old woman who presented with both type 2 diabetes mellitus and an insulinoma. She had a history of diet-controlled gestational diabetes and developed symptomatic fasting and nonfasting hypoglycemia immediately postpartum. She presented for evaluation of hypoglycemia 3 months postpartum. The episodes of hypoglycemia occurred during fasting with the lowest documented blood glucose being 2.16 mmol/L (39 mg/dL), but also occurred between meals and at night. Additionally, she also had many glucose values above 11.1 mmol/L (200 mg/dL) meeting the criteria for type 2 diabetes mellitus. A 72-hour fast led to a documented episode of symptomatic hypoglycemia accompanied by elevated insulin levels after 8 hours (glucose 2.3 mmol/L [42 mg/dL], 69.5 pmol/L [insulin 10 μIU/mL]). Abdominal computed tomography and abdominal ultrasound were normal, but pancreatic venous sampling localized a lesion in the distribution of the splenic artery, and intraoperative ultrasound revealed a 1.5-cm mass abutting the splenic artery. She underwent distal pancreatectomy, and pathology and immunohistochemistry showed an insulin-producing neuroendocrine tumor. After surgery, the hypoglycemia resolved and the patient had persistent hyperglycemia. This case describes the simultaneous presentation of both an insulinoma and type 2 diabetes mellitus before resection of the tumor.

Congenital Hyperinsulinism: Pancreatic [18F]Fluoro-l-Dihydroxyphenylalanine (DOPA) Positron Emission Tomography and Immunohistochemistry Study of DOPA Decarboxylase and Insulin Secretion

Congenital hyperinsulinism (HI) is characterized by hypoglycemia related to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism share a similar clinical presentation, but their treatment is dramatically different. Preoperative differential diagnosis was based on pancreatic venous sampling, a technically demanding technique. Positron emission tomography (PET) after injection of [18F]fluoro-L-DOPA (L-dihydroxyphenylalanine) has been evaluated for the preoperative differentiation between focal and diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]fluoro-L-dopa into dopamine by DOPA decarboxylase. We propose to validate this test by immunohistochemical approach. Pancreatic surgical specimens of four focal and three diffuse HI were studied, using anti-DOPA decarboxylase and proinsulin antibodies. The effect of an inhibitor of DOPA decarboxylase (carbidopa) on insulin secretion was evaluated in vivo and in cultured INS-1 cells. Immunohistochemical detection of DOPA decarboxylase showed diffuse staining of Langerhans islets in the whole pancreas in all diffuse cases, in contrast with dense focal staining in all focal cases. Staining of Langerhans islets outside the focal lesion was diffusely but weakly positive. We correlated the localization of DOPA decarboxylase and proinsulin in normal pancreas and in both diffuse and focal HI tissues. The diffuse PET uptake found before treatment in one child with diffuse HI disappeared completely after carbidopa administration, suggesting in vivo that pancreatic cells can take up amine precursors and contain DOPA decarboxylase. The insulin secretion measured in the supernatant was the same whether INS-1 cells were treated by dopamine or Lodosyn or untreated. We validate PET with as a consistent test to differentiate diffuse and focal HI.

Nouveautés radiologiques dans le dépistage et le diagnostic des erreurs innées du métabolisme

New metabolic diseases are regularly identified by a genetic or biochemical approach. Indeed, the metabolic diseases result from an enzymatic block with accumulation of a metabolite upstream to the block and deficit of a metabolite downstream. The characterization of these abnormal metabolites by MRI spectroscopy permitted to identify the deficient enzyme in two new groups of diseases, creatine deficiencies and polyol anomalies. Creatine deficiency is implicated in unspecific mental retardation. A low peak of creatine at MRI spectroscopy is evocating of creatine deficiency which is treatable by creatine administration. Deficiency of synthesis of polyols, metabolites on the pentose pathway, represent new described metabolic diseases with variable symptoms including a neurological distress, liver disease, splenomegaly, cutis laxa and renal insufficiency. The deficit of ribose-5-phosphate isomerase, one of the enzymes whose diagnosis is evoked in front of the accumulation of ribitol, arabitol and xylitol leads to a leucodystrophy in adults. This new deficit was highlighted by the identification of an abnormal peak in cerebral MRI-spectroscopy corresponding to the abnormal accumulation of polyols in brain. Congenital hyperinsulinism (HI) is characterized by profound hypoglycaemia related to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism share a similar clinical presentation but their treatment is dramatically different. Until recently, preoperative differential diagnosis was based on pancreatic venous sampling, an invasive and technically demanding technique. Positron emission tomography (PET) after injection of [18F]Fluoro-L-DOPA has been evaluated for the preoperative differentiation between focal and diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]Fluoro-L-DOPA into dopamine by DOPA decarboxylase. PET with [18F]Fluoro-L-DOPA has been validated as a reliable test to differentiate diffuse and focal HI and is now a major differential diagnosis tool in infantile hyperinsulinemic hypoglycaemia.

L'hyperinsulinisme congénital du nouveau-né et du nourrisson

Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycaemias requiring aggressive treatment to prevent severe and irreversible brain damage. Several classifications of HI can be attempted, based on: 1) the onset of hypoglycemia in the neonatal period or later in infancy; 2) the histological lesion: focal or diffuse; 3) the genetic transmission: sporadic, recessive, or less frequently dominant. The most common underlying mechanism of HI is dysfunction of the pancreatic ATP-sensitive potassium channel (K + ATP). The 2 subunits of the K + ATP channel are encoded by either the sulfonylurea receptor gene ( SUR1 or ABCC8) or the inward-rectifying potassium channel gene ( KIR6.2. or KCNJ11), both located in the 11p15.1 region. Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. The distinction between the focal and the diffuse HI is very important, because the treatments are different. To distinguish between focal and diffuse HI, transhepatic catheterisation with pancreatic venous sampling was the reference technique, but will likely be replaced by [ 18F] Fluoro-L-Dopa PET scan, which is easier to perform. In absence of response to the medical treatment (diazoxide) a limited pancreatectomy permits to cure focal HI, while a diffuse HI requires a subtotal pancreatectomy with high risk of subsequent diabetes mellitus.

Nesidioblastosis: An Old Term and a New Understanding

Nesidioblastosis is a clinically, pathologically, and genetically heterogeneous disease. Differences between well described forms in neonates with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and rare forms in adults are described. Histopathologic criteria include hypertrophic islets occasionally showing beta cells with pleomorphic nuclei, ductuloinsular complexes, and neoformation of islets from ducts. These changes can be found as diffuse or focal forms of nesidioblastosis. Although most cases occur sporadically, several genetic defects ( SUR1, Kir6.2, GCK, and GLUD1 genes) have been described in neonates. In adults a higher rate of nesidioblastosis is observed in conjunction with multiple endocrine neoplasia type 1. The disease is diagnosed biochemically by a supervised fasting test in adults and in neonates by determining the glucose requirements to maintain normoglycemia, inappropriately high insulin and c-peptide levels, low free fatty acid and ketone body concentrations, glycemic response to glucagons, and the absence of ketonuria. If all highly selective noninvasive imaging techniques fail to identify a tumor, selective arterial calcium stimulation testing for gradient-guided surgery in adults and percutaneous transhepatic pancreatic venous sampling in neonates should be performed. a 95% pancreatectomy is necessary in neonates with a diffuse form of nesidioblastosis, whereas focal forms can be treated by partial pancreatectomy.

Persistent hyperinsulinemic neonatal hypoglycemia caused by focal nesidioblastosis. Preoperative diagnosis by pancreatic venous sampling

A female infant with persistent hyperinsulinemic hypoglycemia is described. Persistent euglycemia could not be achieved by diazoxide, somatostatin and frequent, low protein feeds. Preoperative localization of focal insulin hypersecretion by percutaneous pancreatic venous sampling allowed excision of only a small pancreatic portion which was followed by normalization of blood glucose levels.

Partial elective pancreatectomy is curative in focal form of permanent hyperinsulinemic hypoglycaemia in infancy: A report of 45 cases from 1983 to 2000

Background/Purpose: Permanent hyperinsulinemic hypoglycaemia in infancy (PHHI)I is a severe disease that leads to brain damage. Since 1989, pathologists have identified 2 different forms of the disease: a diffuse form (DiPHHI) and a focal form (FoPHHI). The purpose of this study was to adapt surgical techniques in case of FoPHHI to cure these infants without risk of diabetes. Methods: All patients with PHHI underwent pancreatic venous sampling (PVS) and elective partial pancreatectomy (EPP). Molecular biology and immunohistochemistry were used to ascertain that FoPHHI was a different disease from DiPHHI. Results: 45 EPPs were performed, guided by PVS and peroperative pathology. The lesions were 17 in the head, 4 in the isthmus, 6 in the body, 15 in the tail of the pancreas. Age at surgery ranged from 25 days to 4 years. Two patients already had been operated on elsewhere, and the focal lesion could be found at second operation. All 45 patients except one, were cured with euglycemia at both fasting and hyperglycaemic tests. Molecular biology has shown a specific anomaly in FoPHHI, which never has been encountered in DiPHHI. Conclusions: PHHI is not a homogeneous disease. In one third of cases, only a small amount of endocrine pancreas is abnormal, and conservative surgery is mandatory. The pre- and perioperative conditions to point out the focal pancreatic lesion are described. J Pediatr Surg 37:155-158. Copyright © 2002 by W.B. Saunders Company.

Pancreatic arterial calcium stimulation in the diagnosis and localisation of persistent hyperinsulinemic hypoglycaemia of infancy.

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is often resistant to medical therapy. Surgery is therefore necessary. It is due to focal adenomatous islet-cell hyperplasia treatable by partial pancreatectomy, or diffuse beta-cell hyperfunction, which requires near-total pancreatectomy. Pancreatic venous sampling (PVS) is the reference technique for the preoperative diagnosis and localization of focal forms of PHHI in the pancreas. However, hypoglycaemia is necessary to analyse the results and PVS is technically challenging. Pancreatic arterial calcium stimulation (PACS) is technically easier and does not require hypoglycaemia. To study the accuracy in the diagnosis and localization of PHHI. PACS was performed in 12 patients and correlated with histology. The accuracy of PACS is poor in diffuse lesions since only two of six cases were correctly identified by this test. Five of six focal lesions were correctly recognized and located. PACS is less accurate than PVS in PHHI. Currently, it should be performed only when PVS fails.

Insulinoma and islet cell hyperplasia: value of the calcium intraarterial stimulation test when findings of other preoperative studies are negative.

To evaluate the efficacy of the intraarterial calcium test in localizing sources of hyperinsulinism that remain undetectable at preoperative morphologic studies. Twenty-four patients with clinically proved endogenous hyperinsulinism due to tumorous insulin production were prospectively enrolled. They underwent ultrasound (US), computed tomography, magnetic resonance imaging, endoscopic US, abdominal arteriography, and a calcium test, in which insulin concentrations were measured in hepatic venous blood after selective intraarterial calcium stimulation. The results of the calcium test in seven patients (five women, two men; age range, 30-66 years; mean age, 47 years) with negative findings of morphologic studies are described. Six solitary insulinomas (mean diameter, 0.73 cm) and one nodular hyperplasia were diagnosed after surgery. In all seven cases, calcium test findings allowed accurate localization of the pathologic source of insulin secretion. In three of these seven cases, results of arterial calcium stimulation with hepatic venous sampling (ASVS) affected intraoperative management. An increase in insulin concentration after stimulation in the hepatic artery was not observed, making hepatic metastases unlikely. ASVS, which is procedurally simpler than transhepatic pancreatic venous sampling, is effective for localizing sources of hyperinsulinism not detected with preoperative morphologic studies.

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.

Chronic refractory diarrhoea: a manifestation of endocrine disorders.

Hormonally mediated chronic refractory diarrhoeas constitute a rare but important group which often defy precise diagnosis when conventional routine diagnostic methods are used. Hormonal diarrhoea may occur in carcinoid syndrome, medullary carcinoma of the thyroid, thyrotoxicosis, gastrinoma, VIPoma, glucagonoma, somatostatinoma and systemic mastocytosis. Diagnosis of these conditions depends upon the awareness of clinicians, on clinical features and on documentations of high circulating hormones, if required, by using provocative tests. Precise localization of the tumours may be accomplished by ultrasonography, computerised axial tomography, angiography, percutaneous transhepatic portal and pancreatic venous sampling for the estimation of hormone concentrations. Benign tumours are removed surgically. Malignant neoplasms are treated either by surgery or chemotherapy depending upon the progress of the disease. Diarrhoea usually ceases when hormone levels are normalized following successful treatment.

Localization of small islet-cell tumors. Preoperative and intraoperative ultrasound, computed tomography, arteriography, digital subtraction angiography, and pancreatic venous sampling.

A total of 42 islet-cell tumors were examined between 1972 and 1984. Problems of localization were only encountered in 31 tumors less than 2 cm in diameter. Of 31 small tumors, 27 were correctly localized using a combined diagnostic approach: ultrasound was successful in 12/20 tumors, CT in 9/21, angiography in 20/31, intraarterial digital subtraction angiography in 1/2, and pancreatic venous sampling in 13/16. The smallest tumor found by ultrasound and CT was 7 mm in diameter. Intraoperative ultrasound demonstrated all 9 insulinomas examined. Currently, the most useful techniques for localizing small islet-cell tumors are ultrasound, CT, and angiography. CT is particularly useful for tumor staging. Improvement of non-invasive diagnostic techniques will obviate the need for transhepatic blood sampling.

Localization of neuroendocrine tumors of the pancreas.

The diagnosis of neuroendocrine tumors of the pancreas is based on clinical, biochemical, and ultrastructural data. The different radiological modalities are employed only for localization, except in the case of nonfunctioning neoplasms, for which a differential diagnosis from adenocarcinoma can be suggested based on the radiographic images. Generally, the initial evaluation should consist of the noninvasive studies and should be complemented by angiography and, in cases of functioning neoplasms, with pancreatic venous sampling if the preliminary findings are inconclusive. However, the localizing work-up should be terminated when the information obtained is sufficient to determine the therapy that will follow. If the ultrasonic or computed tomographic findings preclude surgical resection, further work-up is obviously unnecessary.

CT of pancreatic islet cell tumors.

In 41 patients with clinical evidence of pancreatic islet cell tumors, CT detected 21 of 27 tumors that were proved at surgery (sensitivity 78%) and correctly excluded the diagnosis in 14 of 14 patients with no evidence of tumor at long-term follow-up. Using rapid sequence CT scanning and bolus contrast material infusion, a vascular blush was identified in 13 of 16 tumors (81%). Tumors as small as 0.9 cm were localized. CT identified all malignant tumors, and staging accuracy was 100%. CT is useful as the initial imaging procedure for the diagnosis and staging of suspected islet cell tumors. Pancreatic venous sampling and angiography are complementary to CT for the detection of smaller lesions.

Ultrasonic demonstration of small pancreatic islet cell tumors.

AbstractIn three patients real‐time sonography successfully localized small pancreatic islet cell tumors measuring 7, 8, and 17 mm in size. Ultrasound is suggested as the initial radiologic examination for localization of endocrine pancreatic tumors. If ultrasound is negative or equivocal, computerized tomography, arteriography, and pancreatic venous sampling are indicated.