Calcium Stimulation Test Research Articles

Primary Lymph Node Gastrinoma or Occult Duodenal Microgastrinoma With Lymph Node Metastases in a MEN1 Patient

Gastrinoma tissue has been found frequently in lymph nodes located near the duodenum without a known primary tumor. Therefore, it has been suggested that a primary lymph node gastrinoma exists. We report on a 38-year-old woman suffering from multiple endocrine neoplasia type 1 (MEN1) confirmed by menin gene mutation analysis. MEN1 disease started with primary hyperparathyroidism followed by Cushing disease, the detection of tumors of the pituitary, adrenal cortex, and the pancreas and also an elevated serum gastrin level. An octreotide scan revealed 4 tumors in the upper abdomen. A selective arterial calcium stimulation test located the source of the hypergastrinemia to the area of the gastroduodenal and the superior mesenteric arteries. Total pancreatoduodenectomy was performed and conventional histopathologic examination revealed a well-differentiated cystic neuroendocrine tumor of the pancreas expressing glucagon and accompanied by several microadenomas. In addition, 3 suprapancreatic lymph nodes with gastrin-positive endocrine tissue were found. None of the pancreatic microadenomas expressed gastrin and no duodenal endocrine tumor was found despite careful macroscopic examination. Only after complete embedding of the duodenal and pancreatic tissue in 65 paraffin blocks, 2 microgastrinomas (0.45 and 0.8 mm in diameter) were identified in the duodenum. It is concluded that duodenal gastrinomas that give rise to lymph node metastases may be so tiny that they are easily overlooked in a routine examination and that systematic tissue monitoring is required to identify them.

Postprandial Hyperinsulinemic Hypoglycaemia with Positive Selective Calcium Stimulation Test: a case of Idiopathic Reactive Hypoglycaemia.

We report a 48 yo woman admitted for loss of consciousness with a glycaemia of 1.8. Past medical history included vagotomy and Bilroth I procedure for refractory ulcer. BMI was 20. History revealed repetitive postprandial neuroglycopenic symptoms ongoing for several years, with recent syncope. Patient denied alcohol consumption. Several episodes of postprandial hypoglycaemia with hyperinsulinism occurred during hospitalisation, with the lowest two hour postprandial level of 1.9 mmol/L with high insulin 74 pmol/L and C-peptide 1.13 nmol/L values. The venous glycaemia after a forty hour fast was 3,0 mmol/L with low insulin of 2,8 pmol/L. Sulfonylurea screen was negative. Peak Cortisol after cosyntropin stimulation reached 721 nmol/L. Anti-insulin antibodies were negative. An OGTT and nuclear gastric emptying test were normal. Ct scan of the abdomen and endoscopic ultrasonography of the pancreas were normal. Because of the hyperinsulinism, selective intraarterial pancreatic stimulation test was done. Calcium gluconate was injected sequentially in the hepatic, gastroduodenal, superior mesenteric and splenic arteries with measurement of insulin in the hepatic vein between 0 and 120 seconds: strong insulin stimulation was observed only with the splenic artery test, with insulin rising from 12,2 at 0 seconds to 193,2 pmol/L at 60 seconds. Although diazoxide prevented major hypoglycemias, it caused oedema and hirsutism. Partial pancreatectomy of body and tail revealed to be curative with improved quality of life. Pathology report was normal, confirming the idiopathic reactive hypoglycaemia. Long term follow-up will be needed to screen for diabetes or recurrence of hypoglycaemia.

Calcium-stimulation test for the assessment of β-cell function in cats

To assess the potential of an intravenous calcium-stimulation test (CST) as an indicator of insulin secretion in cats, indices calculated from CST results were compared with indices of insulin secretion derived from an intravenous glucose tolerance test (ivGTT) and hyperglycaemic glucose clamp (HGC) in 11 healthy, normal glucose tolerant, conscious cats. Intravenous administration of 2.5 mg/kg Ca 2+ resulted in a significant increase in plasma free Ca 2+ ( P < 0.001) and plasma insulin ( P = 0.047) concentrations but did not affect the plasma glucose concentration. The indices of insulin secretion based on the CST did not correlate significantly with corresponding indices based on the ivGTT and HGC. In conclusion, the CST is not a useful test for assessing insulin secretion in cats. Other indices of insulin secretion, such as fasting insulin concentrations and the homeostasis model assessment of β-cell function (HOMA-B), are easier to obtain and correlate better with indices of insulin secretion derived from the HGC, the gold standard technique for assessing insulin secretion.

PAR‐2 activation regulates IL‐8 and GRO‐α synthesis by NF‐κB, but not RANTES, IL‐6, eotaxin or TARC expression in nasal epithelium

The effects of protease-activated receptor-2 (PAR-2) stimulation on inflammation mechanisms of chronic rhinosinusitis (CRS) are still unknown. PAR-2 receptor expression was investigated by immunohistochemistry and Taqman mRNA analysis in the mucosa of different rhinosinusitis entities. In primary nasal epithelial cell cultures, the function of PAR-2 and its ability to produce CXC, CC chemokines, and IL-6 were measured by calcium mobilization and stimulation tests. Inhibition tests were performed using cortisone, serine protease inhibitors, cysteine protease inhibitors, Pertussis toxin (PTX) and nuclear transcription factor (NF-kappaB) inhibition (BAY 11-7085). Signal transduction pathways were analysed by electromobility shift assays (EMSA) and NF-kappaB binding studies. The expression of PAR-2 was found to be increased in CRS specimens. The activation of PAR by trypsin or PAR-2-specific activating peptide (AP) caused an increase in cytosolic calcium, as well as the release of the CXC chemokines IL-8 and growth-related oncogene (GRO)-alpha, but not the release of CC chemokines or IL-6. AP-induced CXC chemokine was sensitive to PTX and activation of NF-kappaB was inhibited by BAY11-7085. Furthermore, a serine protease inhibitor significantly inhibited chemokine synthesis stimulated by trypsin and culture supernatants of staphylococci, whereas steroids and cysteine protease inhibitors had little effect. PAR-2 plays a role in serine protease-mediated regulation - staphylococcal and non-staphylococcal origin - of IL-8 and GRO-alpha in nasal epithelial cells, but not in the regulation of CC chemokines. PAR-2 may therefore be involved in the pathophysiology of CRS and NP at different sites of activation, namely (i) proteases, (ii) the PAR-2 receptor itself or (iii) the application of novel agents that block NF-kappaB/IkappaB-alpha signalling.

The Role of Intra-Arterial Calcium Stimulation Test with Hepatic Venous Sampling (IACS) in the Management of Occult Insulinomas

Occult insulinomas remain a clinical challenge. Specifically designed protocols are necessary to aid detection and facilitate a focused pancreatic exploration. Seventeen non-multiple endocrine neoplasia (non-MEN) patients referred to this medical center in the past 10 years because of equivocal diagnosis, failure of previous operation or difficulty in localization for insulinomas were studied. A routine intra-arterial calcium stimulation test with venous sampling (IACS test) was done for lesion localization. An exploratory laparotomy with intraoperative ultrasound (IOUS) examinations was performed. Preoperative imaging (sonography, high-resolution computed tomography scan, and magnetic resonance imaging) found six insulinomas, and IOUS found an additional six in the pancreatic regions; all were compatibly indicated by the IACS test. The remaining five patients with occult lesions by IOUS were treated by 40% (1) or 60-70% (4) distal pancreatectomies when insulin gradients were demonstrated on calcium stimulation to the splenic or to the superior mesenteric artery, respectively, and nesidioblastosis was found in each pathology examination. There were no complications related to the arterial stimulation and venous sampling (ASVS) test. No patient had recurrent hyperinsulinism, permanent morbidity, or mortality from surgery. IACS test helps in the diagnosis of equivocal pancreatogenous hypoglycemia, indicating the pancreatic region of priority exploration and guiding a pancreatic resection.

Laparoscopic Spleen-Preserving Distal Pancreatectomy as Treatment for Nesidioblastosis after Gastric Bypass Surgery

Nesidioblastosis is characterized by hyperfunction of pancreatic islets caused by hypertrophic beta cells. Postprandial symptoms of hypoglycemia are the clinical presentation of the disease. A female patient with diabetes mellitus who underwent a Roux-en-Y gastric bypass began to present postprandial symptoms of hypoglycemia. There was no radiologic (MRI) evidence of insulinoma. Selective arterial calcium-stimulation test identified hyperfunction only in the splenic artery. Laparoscopic spleen-preserving distal pancreatectomy was performed. The patient has been entirely free of any postprandial symptoms for 10 months after the partial pancreatectomy.

Intraoperative Ultrasound with Palpation is Still Superior to Intra‐arterial Calcium Stimulation Test in Localising Insulinoma

This study assessed the sensitivities of preoperative localisation modalities such as computed tomography (CT), magnetic resonance imaging (MRI), arteriography and arterial stimulation venous sampling (ASVS) using serum insulin and C-peptide gradients to intraoperative techniques in localising insulin-secreting tumours in our institution. Fourteen patients with proven insulinoma, aged 20-66 years, who presented from 1997 to 2004, were studied retrospectively. All patients underwent ASVS where C-peptide and/or insulin gradients were calculated. The results were compared with the preoperative findings of CT, MRI, arteriography, as well as intraoperative ultrasound and palpation. Intraoperative ultrasound with palpation correctly localised 10 of the 11 tumours with a sensitivity of 91%. Sensitivities of other localisation techniques were lower: 31% by CT, 50% by MRI, and 46% by arteriography. ASVS with insulin gradients alone allowed accurate localisation in 40% of patients while localisation using only C-peptide gradients of more than 2 was 43%. The insulinomas, measuring 10-30 mm, were successfully removed in 13 patients--6 from the body, 4 from the tail, 2 from the head and 1 from the junction of the body and tail. All except 1 were cured by selective surgery and remained free of hypoglycaemia over the next 2-60 months of follow-up. One patient had left lobectomy due to liver metastases from a malignant insulinoma and remained asymptomatic with medical therapy. Intraoperative ultrasound with palpation is a highly sensitive method for the localisation of insulinoma compared with other preoperative localisation techniques.

A Case of Insulinoma Associated with Type 2 Diabetes Mellitus

An insulinoma is an endocrine tumor of the pancreas derived fro m the beta cells with abnormal insulin secretion. An insulinoma is rare, the incidence being estimated at only four per one million person-years. The association of diabetes mellitus and insulinoma is extraordinarily rare, but we should not overlook an insulinoma as a possible cause of hypoglycemia in patients with diabetes mellitus. A 70-year-old diabetic man who had been treated with oral hypoglycemic agents for type 2 diabetes suffered from night sweating for 10 days. Even after he stopped taking h is oral hypoglycemic agents, the night sweating continued. The patient was admitted to evaluate the cause of the recurrent hypoglycemic events. After a 72-hour fasting test and selective arterial calcium stimulation test with venous sampling, he was diagnosed with insulinoma accompanied by type 2 diabetes mellitus. In the course of the study, the patient was also incidentally diagnosed with lung cancer. (J Kor Diabetes Assoc 31:517~519, 2007)

Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)

Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease. Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests. All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation. Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.

Propoxyphene-Induced Hypoglycemia in Renal Failure

To present a case of symptomatic hypoglycemia induced by propoxyphene. The historical features, results of laboratory evaluations, and clinical course of a man with end-stage renal disease in whom hypoglycemia developed during treatment with propoxyphene are described. A 54-year-old man with chronic renal failure had recurrent episodes of hypoglycemia (plasma glucose level, 40 mg/dL). While he continued treatment with propoxyphene, 58 hours into a 72-hour fast the plasma glucose concentration was 38 mg/dL, in conjunction with a beta-hydroxybutyric acid level of 0.9 mmol/L and inappropriately elevated plasma insulin, serum C-peptide, and proinsulin levels. A plasma drug screen was negative for sulfonylureas. A selective arterial calcium stimulation test yielded negative results. A 72-hour fast after discontinuation of propoxyphene therapy resulted in no hypoglycemia, and he experienced no hypoglycemic episodes for at least 2 years after withdrawal of the propoxyphene treatment. The importance of obtaining a thorough medication history in a patient with renal failure and hypoglycemic episodes is highlighted by this case of propoxyphene-induced hypoglycemia. The mechanism of this effect is not known, although non-micro receptor agonism or noncompetitive N-methyl-D-aspartate receptor antagonism may have a role in causing hypoglycemia.

Hyperinsulinemic Hypoglycemia with Nesidioblastosis after Gastric-Bypass Surgery

We describe six patients (five women and one man; median age, 47 years; range, 39 to 54) with postprandial symptoms of neuroglycopenia owing to endogenous hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass surgery. Except for equivocal evidence in one patient, there was no radiologic evidence of insulinoma. Selective arterial calcium-stimulation tests, positive in each patient, were used to guide partial pancreatectomy. Nesidioblastosis was identified in resected specimens from each patient, and multiple insulinomas were identified in one. Hypoglycemic symptoms diminished postoperatively. We speculate that hyperfunction of pancreatic islets did not lead to obesity but that beta-cell trophic factors may have increased as a result of gastric bypass.

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.

Abnormalities of proinsulin processing in functioning insulinomas: clinical implications.

Abnormal proinsulin processing in insulinomas may result in secretory granules containing both insulin and proinsulin, a finding not encountered in healthy beta-cells. The aim of this study was to test whether such abnormalities in the proinsulin to insulin conversion have clinical implications in patients with hypoglycaemic disorders. Case-series. Fifteen patients with histologically confirmed insulinoma and two patients with islet cell hyperplasia were included. The immunohistochemical distribution pattern of proinsulin within the tumour cells was classified as Golgi pattern (predominantly perinuclear immunolabelling) or diffuse pattern (immunolabelling in the periphery of the cells, indicating the presence of proinsulin in secretory granules). Data obtained from the 72-h fast and arterial calcium stimulation and hepatic venous sampling (ASVS) test were related to the morphological classification. Six insulinomas exhibited a diffuse proinsulin distribution pattern, while nine insulinomas and two islet cell hyperplasias disclosed a Golgi pattern. Median proinsulin concentrations at the termination of the fast tended to be higher in patients with the diffuse proinsulin distribution pattern than in patients with the Golgi pattern (86.9 vs. 18.8 pmol/l, P = 0.07). Higher insulin (P < 0.005) and proinsulin (P < 0.05) concentrations were significantly correlated with earlier occurrence of hypoglycaemia during the prolonged fast. During the ASVS test, tumours with the diffuse proinsulin distribution pattern exhibited a higher increase in both insulin (median, 37.3- vs. 10.5-fold, P < 0.05) and proinsulin (6.3- vs. 1.6 fold, P < 0.005) concentrations following calcium stimulation than the tumours with the Golgi pattern. Abnormalities in the proinsulin to insulin conversion in patients with insulinomas and islet cell hyperplasia correlate with impaired regulation of both insulin and proinsulin secretion during the prolonged fast as well as the ASVS test.

Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is related to two main histological pancreas anomalies: focal adenomatous hyperplasia and diffuse beta-cell hypersecretion. Pharmacological tests to measure acute insulin responses (AIR) to peripheral i.v. injections of glucose, calcium, and tolbutamide have been reported as potential means to distinguish between these histological forms. In patients with defects in ATP-sensitive potassium channels, tolbutamide will fail to induce insulin release in affected portions of the pancreas, whereas calcium gluconate will enhance insulin release through spontaneously active voltage-gated Ca(2+) channels. Consequently, in focal CHI patients, calcium should promote AIRs from the lesion, whereas tolbutamide should act to promote insulin secretion from the healthy region of the pancreas (outside the focal hyperplasia). We therefore studied AIRs to calcium and tolbutamide stimulation tests in 16 children with focal (n = 9) or diffuse (n = 7) CHI before pancreatic surgery. We found hypervariable AIRs to glucose and calcium stimulation in both focal and diffuse CHI patients. AIRs to tolbutamide stimulation were found modest in focal CHI patients, which might account for beta-cell quiescence in the healthy portion of the pancreas of these patients. We conclude that AIRs to calcium and tolbutamide stimulation tests are not sufficient to differentiate the focal from the diffuse CHI patients.

Intra-arterial calcium stimulation test for detection of insulinomas: detection rate, responses of pancreatic peptides, and its relationship to differentiation of tumor cells

The selective intra-arterial calcium stimulation test has greatly facilitated the precise regionalization of insulinomas smaller than 2 cm, which noninvasive techniques (ultrasound [US], computed tomography [CT], magnetic resonance imaging [MRI]) often fail to localize. This study examined not only the role of the test in the localization of insulinomas, but also the responsiveness of 3 β-cell peptides (insulin, C peptide, and proinsulin) and their relationship to the degree of differentiation of the tumor cells, using percentage decrease of both proinsulin/insulin (P/I) and proinsulin/C peptide (P/C) ratios after stimulation as indices. Ten consecutive surgically proven insulinoma patients each received an injection of calcium into the arteries supplying the pancreas after standard selective angiography and β-cell peptide levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, and 180 seconds after each injection prior to operation. After surgery, the expressions of the calcium sensing receptor (CaSR) on the resected tumors were assessed by immunohistochemistry. Intra-arterial calcium stimulation with sampling either for insulin or for C peptide correctly predicted the site of insulinoma in 8 of 9 patients or in 7 of 8 patients if the 2 big malignant insulinomas were excluded; thus, the detection rate of this test was 89% and 88%, respectively. Calcium administration stimulated a marked and prompt release of insulin and C peptide simultaneously. Both peaked within 30 to 60 seconds, then declined gradually thereafter, remaining above the baseline at 180 seconds. The magnitude of increase correlated well with the corresponding percentage decrease of P/I and P/C ratios. The response of proinsulin was much less. Immunohistochemistry demonstrated variable membraneous staining for CaSR in normal pancreatic islets and in about 9% of the total normal β cells, whereas staining in tumor cells was only minimally detectable. We conclude that selective intra-arterial calcium stimulation with hepatic venous sampling either for insulin or for C peptide is a highly sensitive method for the preoperative localization of small insulinomas. Calcium injection stimulates a brisk response of insulin, C peptide, and proinsulin simultaneously and the magnitude of increase of both insulin and C peptide appears to be correlated well with the degree of differentiation of the tumor cells. The exact mechanism by which calcium provokes the release of β-cell peptides is less clear and whether the CaSR is involved in the mechanism of its action requires further study.

Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism

Nesidioblastosis in adults has been reintroduced into the differential diagnosis of organic hyperinsulinism by the description of 'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. Pathologic specimens of all adult patients (n = 66) operated on for organic hyperinsulinism were re-examined. Five patients fulfilled the histomorphological criteria of nesidioblastosis. Retrospective review of clinical presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre- and intraoperative localization studies and surgical therapy was performed. In contrast to NIPHS, fasting tests became positive after 8-14 h. Tolbutamide tests were positive and preoperative imaging showed negative results in all patients. At first operation distal pancreatic resections were performed in three patients, resection of the pancreatic body in one patient and biopsy of the pancreatic tail in one patient. Two of three patients with recurrent disease had to be reoperated. One patient showed a coexistence of nesidioblastosis and multiple small insulinomas and is part of a kindred with autosomal dominantly inherited 'familial islet-cell adenomatosis'. Surgical exploration is indicated only after thorough biochemical diagnosis. An aggressive strategy for preoperative localization including selective arterial calcium stimulation testing seems justified. There may be a combination of nesidioblastosis and islet cell tumours. A link between beta-cell hyperplasia and progression to insulinoma based on not yet known genetic causes can be suspected.

Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas.

ObjectiveTo determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas.Materials and MethodsSeven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery.ResultsEight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization.ConclusionSelective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem to be helpful in assessing tumor location, but further study is needed.

67-Year-Old Woman With Recurrent Hypoglycemia

67-Year-Old Woman With Recurrent Hypoglycemia

Noninsulinoma pancreatogenous hypoglycemia syndrome: An update in 10 surgically treated patients

Background. Neuroglycopenia from endogenous hyperinsulinism usually is caused by insulinomas in adults. We recently reported a novel hypoglycemic disorder in 5 patients (patients 1 to 5) with postprandial neuroglycopenia, negative 72-hour fasts, negative perioperative imaging studies, but positive calcium stimulation tests and islet hypertrophy and nesidioblastosis in the gradient-guided resected pancreata. Methods. In this report we compare our experience with 5 additional patients (patients 6 to 10) with this syndrome to that in the original report. Results. The clinical features of patients 6 to 10 were similar to those of patients 1 to 5. Each had positive calcium stimulation testing that guided the extent of the distal pancreatectomy and histologic evidence of islet cell hypertrophy or nesidioblastosis. All 10 patients are alive from 9 to 50 months after operation, 1 of whom had no amelioration of neuroglycopenia. Minor perioperative complications occurred in 3 patients. One patient has experienced repeated bouts of acute pancreatitis, pseudocyst formation, and exocrine insufficiency. Conclusions. We have identified adult patients with severe, postprandial hyperinsulinemic hypoglycemia from diffuse islet cell disease, 80% of whom have been well palliated with surgery. The results in 7 men have been better than those in the 3 women for reasons that are not obvious. (Surgery 2000;128:937-45.)

Non-insulinoma pancreatogenous hypoglycaemia syndrome

Abstract Background The authors have reported a newly recognized hypoglyacemic disorder, non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), which is characterized by postprandial hyperinsulinaemic hypoglycaemia, negative 72-h fast, negative transabdominal and intraoperative ultrasonography, spiral computed tomography and coeliac axis angiography, positive selective arterial calcium stimulation test (SACST), absence of insulinoma but presence of islet hypertrophy and nesidioblastosis, and relief of symptoms from gradient-guided partial pancreatectomy. Experience with the next five patients with this disorder (6–10; 1998–1999) compared with the original five (1–5; 1996–1998) is reported. Results Wide age range, male predominance, postprandial occurrence of symptoms, negative radiological localization, nesidioblastosis/islet hypertrophy, but no insulinoma characterized all ten cases. Response to SACST indicated widespread islet hyperfunction in patients 1 and 5; limitation to distribution of the SPA and GDA in patients 3, 4, 6 and 8, to distribution of the SPA in patients 2, 7 and 9, and to distribution of the SMA in patient 10. Except for patient 5, pancreatic resection to the left of the SMV was performed when only the SPA was positive on the SACST. Patients 5 and 8 have had recurrence of symptoms; they resolved within 3 months for patient 5. Conclusion NIPHS can usually be treated successfully with gradient-guided partial pancreatectomy.