Intra-arterial Calcium Stimulation Test Research Articles

MON-911 Debilitating Neuropsychiatry Symptoms in Pancreatic Insulinoma Co-Secreting Serotonin and IGF-1

Background:Insulinoma is the most common type of functioning pancreatic neuroendocrine tumor (NET). Polyhormonal secretions from the NET, giving rise to distinct clinical symptoms such as carcinoid symptoms are rare. Clinical Case: We report a 68-year-old woman who presented with four months history of recurrent diaphoresis, palpitations, tremors and chest tightness. These were associated with episodic paroxysms of flushing and diarrhoea. The physical examination was unremarkable. She was a well-nourished woman with BMI of 28 kg/m2. Initial laboratory tests ruled out any renal, liver abnormalities with normal cortisol and thyroid function test. Further evaluation confirms insulin mediated hypoglycaemia with low random blood sugar 2.5 mmol/l (4.4-7.8) and failure to suppress C-peptide, 1092 pmol/L (298-2350) and insulin levels, 12.7 mU/L (3-25). Urine 5-HIAA was markedly elevated 2430.37 µmol/day (3.66-42.89) with borderline elevation of serum chromogranin A level 122 ng/mL (27-94). IGF-1 was also raised at 416 ug/L (91-282). Two months later she presented with new onset of delirium, incoherence, agitation and restlessness independent of her hypoglycaemic events. These symptoms deteriorated and fluctuates throughout the day with period of normalcy in between. This has led to requirement of a full time caregiver for her. Cranial CT excluded any brain pathology. We are faced with a diagnostic challenge to localize the primary lesion as radiological imaging so far were normal. GALLIUM-68 PET CT showed physiological uptake in the uncinate process of the pancreas (SUVmax 14.4). Endoscopic ultrasound of the pancreas was normal. An intra-arterial calcium stimulation test with hepatic venous sampling (ASVS) confirms a lesion at the head of pancreas with two times increment of insulin from baseline at the gastroduodenal artery distribution. Despite elimination of hypoglycaemic events with Diazoxide 100mg twice daily, her neuropsychiatric symptoms persisted. We postulate that this might be from excessive peripheral production of serotonin by the pancreatic carcinoid tumour or a niacin deficiency state because of metabolic diversion of its precursor, tryptophan. Conclusion:This case highlights the occurrence of debilitating neuropsychiatry manifestations in a likely neuroendocrine tumour arising from the head of pancreas secreting insulin, serotonin and IGF-1.

Selective intra-arterial calcium stimulation test for the localization of insulinomas: an Australian hospital experience.

Insulinomas are rare tumours of the pancreas and the most common cause of hypoglycaemia in non-diabetic adults. They can be cured by surgery but require precise localization. The aim of this study was to assess the utility of the selective intra-arterial calcium stimulation test (SIACST) in patients with an insulinoma to correctly localize the tumour. Medical records of patients with a diagnosis of insulinoma or who underwent an SIACST were retrospectively reviewed. Localization of lesions by SIACST was compared to endoscopic ultrasound and radionuclide imaging studies and verified against findings at surgery. A total of 24 patients (mean age 58 years, 16 females, 20 with insulinoma) underwent SIACST. The SIACST correctly localized the insulinoma in 17 of 20 patients (85%). Localization rate for computed tomography was 55% and 75% for endoscopic ultrasound and glucagon-like peptide-1 receptor scan. SIACST provided incremental diagnostic information in patients with insulinoma who had equivocal non-invasive imaging preoperatively. This technique remains an essential diagnostic tool when a lesion is not localized by other methods.

ПОВТОРНЫЕ ОПЕРАТИВНЫЕ ВМЕШАТЕЛЬСТВА ПРИ ИНСУЛИНОМАХ

Insulinoma is the most common pancreatic neuroendocrine tumor. Surgical management of insulinomas is considered to be the only curative method. However pancreatic surgery is associated with postoperative complications. The most difficult category of patients is patients previously operated on the pancreas. The aim is to show our experience of treatment patients with reoperated insulinomas. Materials and methods. 201 patients were operated because of insulinoma in the abdominal surgery department of Sechenov University from 1993 to 2019. 18 patients of them were reoperated. The authors describe their treatment experience of this category of patients. Results. The rate of reoperations in pancreatic insulinomas was 9%. Most of the tumors (12 of 18) were located in the head. Six patients were reoperated due to newly developed insulinomas. 12 patients were previously operated in other clinics but the tumors were not detected. This group of patients were the most complicated in imaging so we had to apply selective intra-arterial calcium stimulation test. All reoperated patients developed destructive pancreatitis in the postoperative period, five patients developed pancreatic fistula of classes B and C, two patients died. Conclusion. Accurate preoperative imaging carried out by an experienced team in reference center is an important factor for reducing the level of postoperative complications. Patients who had pancreatic surgery before should be treated by experienced multidisciplinary team.

SUN-313 Insulinoma: Secreting but Not Appearing

Introduction: The diagnosis of an insulinoma requires clinical suspicion and confirmatory biochemical testing. Insulinomas are localized using computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography and if needed selective pancreatic arterial calcium injections with measurements of hepatic venous insulin levels (1). Clinical Case: A 71 year old female with no significant past medical history was referred for evaluation of hypoglycemia. She was noted to have frequent episodes of symptomatic fasting and post-prandial hypoglycemia for two years prior to presentation. Symptoms associated with hypoglycemia included: weakness, diaphoresis, and peri-oral numbness which resolved after treatment with high carbohydrate foods or juice. On several occasions severe hypoglycemia required emergency services assistance. Endocrine evaluation at an outside clinic during an episode of hypoglycemia found a serum glucose of 30 mg/dL, elevated insulin level (20 U/ml, n<3.0 U/mL), C-peptide (4.3 ng/mL, n<0.6 ng/mL), and proinsulin (130 pmol/L, n<5.0 pmol/L) levels. All other laboratory work was normal. CT scan of the abdomen localized a lesion to the tail of the pancreas, but based on radiographic appearance differential diagnosis included a splenule. She underwent an endoscopic ultrasound and magnetic resonance cholangiopancreatography of the abdomen both of which were unable to characterize the lesion. Given high clinical suspicion, an intra-arterial calcium stimulation test was conducted, with inconclusive results. A gallium-68 Dotatate scan showed Dotatate uptake, without further distinction. Given the challenge of identifying the lesion, the decision was made in collaboration with radiology to complete a Tectnetium-99m sulfur colloid single-photon emission computed tomography (SPECT)/CT scan. This imaging modality shows accumulation of sulfur colloid in normal splenic tissue and is expected to show no radiotracer uptake in pancreatic tissue (2). The scan showed no significant accumulation in the area of concern presenting high suspicion for a neuroendocrine tumor. Endocrine Surgery completed a partial pancreatectomy with removal of a 1.4 cm tumor. Pathology was consistent with insulinoma. Post-operatively the patient had complete resolution of her hypoglycemia. Conclusion: This case highlights a diagnostic challenge which required interdisciplinary collaboration to use alternative imaging to localize an insulinoma preoperatively.

Applying Intraoperative Insulin Level Monitoring for Tumor Removal in a Patient With Recurrent Pancreatic Multiple Insulinomas

Pancreatic multiple insulinoma is a very rare disease. Surgical treatment is challenging, as the localization of the tumor lesion is rather complicated. We report a case of a 47-year-old woman with recurrent hypoglycemia after distal pancreatectomy for her insulinoma. Multiple insulinomas were found in the first pathology report. Follow-up abdominal computed tomography (CT) did not show any lesion. One suspected tumor at the pancreatic head was found on abdominal magnetic resonance imaging (MRI), whereas the result of the intra-arterial calcium stimulation (IACS) test suggested diffuse β-cell hyperfunction. Using a quick insulin assay, intraoperative blood insulin monitoring demonstrated a decrease in insulin level after the removal of the main tumor during the second surgery. A 75% subtotal pancreatectomy was also performed, and the patient is well with no hypoglycemic attacks or diabetes reported 15 months after the second operation. In addition to intraoperative sonography and manual palpation, intraoperative insulin quick assay may be another useful guide during surgery. Most insulinomas are small, solitary, benign, and intrapancreatic. Multiple insulinomas are common in multiple endocrine neoplasia type 1 (MEN-1), which accounts for approximately 10% of all patients with insulinoma.1 For recurrent insulinoma, preoperative localization and definite complete resection during surgery are challenging issues. There are many available techniques for localization of the insulinoma, including transabdominal ultrasonography, CT, MRI, endoscopic ultrasonography (EUS), angiography, IACS, somatostatin receptor scintigraphy (SRS), positron emission tomography (PET), intra-operative ultrasonography (IOUS) and intra-operative palpation. We present a case that underwent a second subtotal pancreatectomy for recurrent hypoglycemia due to multiple insulinomas. The surgery was performed successfully using intraoperative insulin level monitoring by a new quick insulin assay (an electrochemiluminescent immunoassay).

Invasive Diagnostik bei Insulinomen des Pankreas

Insulinomas are the most common cause for hypoglycemia with endogenous hyperinsulinism. Insulinomas are the most frequent endocrine tumor of the pancreas and 10% occur as multiple tumors (e.g. multiple endocrine neoplasia type I) or in rare cases as islet cell hyperplasia. A further 10-15% of insulinomas are malignant. Non-invasive imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and somatoreceptor scintigraphy (SRN) show a lower sensitivity for detection and localization of tumors, because in many cases insulinomas are smaller than 2 cm in size. Invasive pre-operative diagnostic procedures, such as transhepatic peripancreatic venous blood sampling (TPVB) and the intra-arterial calcium stimulation test (ASVS) are much more time-intensive compared to CT, MRI and US with an examination time of 2-3 h but achieve a more exact pre-operative detection and localization with sensitivities mostly greater than 95% and are therefore the diagnostic methods of choice.

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.

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.

Insulinoma

Insulinoma is the most common pancreatic islet cell tumor, usually presenting with symptoms of neuroglycopenia. Diagnosis depends on a high index of suspicion, together with the demonstration of endogenous hyperinsulinemic hypoglycemia. Although the requirement for preoperative localization is controversial, the minimally invasive but highly sensitive endoscopic ultrasonography allows for a more focused surgery, shorter exploration time, and the option of laparoscopic surgery. Intra-arterial calcium stimulation test can be considered in persistent or possibly multifocal disease. Intraoperative ultrasonography is also recommended to assist tumor localization and minimize complications. The use of a biostator or rapid insulin assays intraoperatively may be helpful if multiple lesions are present. The surgical cure rate for benign insulinomas approaches 100%. For those with residual or metastatic disease, symptomatic control can be achieved with diazoxide or somatostatin analogues. Multimodality therapy is usually required for metastatic disease: with control of hypoglycemia, prolonged symptom-free survival can be expected.

Intra-arterial calcium stimulation test in the investigation of hyperinsulinaemic hypoglycaemia

OBJECTIVETo investigate the use of a calcium infusion test in the diagnosis and localisation of insulin secreting tumours in children.PATIENTSThree patients with persistent hypoglycaemia of infancy (PHHI).PROCEDUREDuring planned selective coeliac...