Selective Arterial Calcium Stimulation Research Articles

18F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature.

Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).

FRI360 A Protracted Course Of Worsening Adrenergic And Neuroglycopenic Symptoms Due To Delay In Diagnosis Of Insulinoma

Abstract Disclosure: A. Karca: None. W. Lai: None. S. Naidoo: None. L.N. Saladi: None. B.C. Jameson: None. A 33-year-old Hispanic male presented with altered mental status, witnessed seizure and hypoglycemia (capillary BG 40mg/dL). Patient and family reported multiple episodes of symptomatic hypoglycemia and progressively worsening adrenergic and neuroglycopenic episodes with altered mental status requiring hospital admissions and evaluation for endogenous hyperinsulinemia in the past several months prior to admission. Patient was admitted to the ICU. Laboratory workup revealed documented hypoglycemia (venous BG 45mg/dL) and inappropriate insulin (17uU/mL, n3-25uU/mL), c-peptide (2.7ng/mL, n0.8-4.2 ng/mL) and pro-insulin (38.3 pmol/L, n<18.8 pmol/L) levels. Sulfonylurea and meglitinide screens were negative. Patient required continuous dextrose infusion as well as octreotide, with enteral feeding, to maintain BG >70mg/dL. Abdominal US, multiple CT scans, endoscopic US failed to locate source of endogenous hyperinsulinemia. Multi-discipline discussion among ICU team, Endocrinology, Interventional Radiology (IR), and Surgery considered MRI versus IR-guided selective arterial calcium stimulation (SACS) vs PET-CT NETSPOT with Ga-68 Dotatate, which had been ordered, but unable to be arranged prior to this admission. Ultimately, MRI with pancreatic protocol revealed 3.5cm exophytic solid mass arising from the tail of the pancreas and patient underwent laparoscopic hand-assisted distal pancreatectomy and splenectomy, with intraoperative ultrasound to confirm the location of the mass. Histologic examination revealed a well-differentiated neuroendocrine tumor. Chart review revealed documented hypoglycemia as far back as eight years prior to this admission, although no further results were available from that time to confirm endogenous source. Possible explanations for delay in diagnosis include patient health literacy, inaccessibility of outpatient testing, limitations of testing modalities, and access to staff skilled in more specialized testing, like PET-CT NETSPOT and SACS. Localizing techniques are divided into pre-operative and intra-operative, with pre-operative techniques further divided into non-invasive and invasive modalities. First line pre-operative testing includes US and CT, which have widely varying sensitivity depending on size and location of the tumor. MRI can have better sensitivity for smaller and distal tumors. PET-CT NETSPOT with Ga-68 Dotatate, has very high sensitivity and specificity in limited studies. If not localized with non-invasive modalities, SACS is an invasive modality with high sensitivity and specificity. Although insulinomas are a rare neuroendocrine tumor with challenging diagnostic workup, higher clinical suspicion with early biochemical workup, patient education, referral to endocrinology, better accessibility of diagnostic testing will help lead to timely diagnosis and management. Presentation: Friday, June 16, 2023

Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report

BackgroundInsulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis.Case presentationOur patient experienced hypoglycemic coma in the 3rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified.ConclusionsAlthough pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia.

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Role of selective arterial calcium stimulation test in the evaluation of hypoglycaemia post Roux-en-Y gastric bypass

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The use of selective arterial calcium stimulation test in the diagnosis of the hyperinsulinemic hypoglycemia

We examined the patients with hyperinsulinemic hypoglycemia who were performed non-invasive imaging techniques with doubtful or failed results. We compared the performances of the Selective Arterial Calcium Stimulation Test (SACST) and non-invasive imaging techniques. Eight patients with hyperinsulinemic hypoglycemia, performed SACST after evaluating with imaging modalities were examined retrospectively. Three patients were diagnosed with Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS), 4 with insulinoma, and 1 with autoimmune hypoglycemia after SACST. While the concordance between the SACST and surgery-proven pathology for insulinoma was 50% (2/4), the accuracy in the localization of insulinoma was 25%. Although SACST does not have high concordance with surgery-proven pathology and accuracy in the localization of insulinoma, it may be preferred in the differential diagnosis of hyperinsulinemic hypoglycemia in medical centers where other imaging techniques are not available, or in cases where other imaging methods obtain suspicious/inadequate diagnosis.

Nesidioblastosis: an uncommon complication seen post Roux-en-Y gastric bypass.

Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication. Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially. The incidence is 0.1-0.3% of all post Roux-en-Y gastric bypass patients. The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases. Pathological specimen of pancreas will show diffuse hypertrophy of beta cells. Management includes acarbose and total or subtotal pancreatectomy, which can be curative. With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.

Adult-onset nesidioblastosis: a challenging diagnosis revealed by glucagon-like-peptide-1 receptor imaging

A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. 68Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months. Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia. The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different. 68Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia. Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis. Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.

Importance of Selective Arterial Calcium Stimulation with Hepatic Venous Sampling in Management of a Patient with Multifocal Insulinoma

Sri Lanka Journal of Medicine is the official journal of the Kandy Society of Medicine. It is a peer-reviewed journal currently published biannually. Original articles, reviews, brief reports, case reports, points of view, and letters to the editor, in all fields of medical science and practice are accepted for publication.The Sri Lanka Journal of Medicine is now indexed in DOAJ

Occult insulinoma with treatment refractory, severe hypoglycaemia in multiple endocrine neoplasia type 1 syndrome; difficulties faced during diagnosis, localization and management; a case report

BackgroundMultiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation.Case presentationA 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m2.She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3rd decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms.ConclusionsRenal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype.

Case Report: A Case of Adult Nesidioblastosis

Background: Adult nesidioblastosis is an extremely rare cause of hyperinsulinaemic hypoglycaemia, however its diagnosis has been on the rise in recent years. It is characterised by beta-cell hypertrophy and diffused islet hyperplasia. In contrast to infantile nesidioblastosis secondary to a genetic defect, the cause of adult nesidioblastosis is largely unknown. Case report: We report a case of hyperinsulinaemic hypoglycaemia in an 83-year-old man with biochemical derangements consistent with a diagnosis of insulinoma. Preoperative cross-sectional imagings, Dotatate PET, and visceral angiogram all failed to definitively localise a neuroendocrine tumour. Selective arterial calcium stimulation showed a subtle increase in insulin secretion from the tail of the pancreas. After an unrevealing intraoperative ultrasound, a distal pancreatectomy was performed with pathology showing diffused islet hyperplasia consistent with a diagnosis of nesidioblastosis. Postoperative euglycaemia was achieved and persisted to the time of manuscript submission four months later. Conclusion: Clinically and biochemically it is extremely difficult to distinguish nesidioblastosis from insulinoma. The sensitivity of different preoperative localising modalities for insulinoma varies with the gold standard being selective arterial calcium stimulation. In contrast to insulinoma, response to selective arterial calcium stimulation could be subtle in nesidioblastosis, and such subtlety should raise the suspicion for the latter especially in the presence of unrevealing imaging findings. Given reports of coexistence of insulinoma and nesidioblastosis along with other known entities such as multifocal insulinoma and focal nesidioblastoma, we postulate pathological beta cell hyperplasias fall on a continuous spectrum of hyperfunctioning beta cell disorders as opposed to the current dichotomous understanding.

The insulinoma as a diagnostically and therapeutically challenging neoplasm

Introduction and purpose
 An insulinoma is the most common neuroendocrine tumor of a pancreas. This tumor produces insulin, which in excess causes hypoglycemic attacks, provoked by hunger or physical effort. Delays in diagnostic processes of the insulinoma are associated with the misattribution of symptoms to cardiac, psychiatric or neurological disorders. Thus, the suitable diagnostic procedures play a significant role as they ensure quick introduction of treatment. The purpose of this work is to evaluate advances in demanding diagnostically and therapeutically insulinoma.
 A brief description of the state of knowledge
 The used method was a literature review. The basic and the most common method of treating the insulinoma is a surgery. Due to this, finding precise location of the tumor preoperatively is crucial. In the diagnostics of the insulinoma both basic CT and MRI contrast enhanced and an endoscopic ultrasound, a selective arterial calcium stimulation test and the latest molecular imaging are used. In treatment process not only traditional surgical excisions were performed, but also laparoscopic and robotic surgeries turned out to be success.
 Conclusions
 Summing up, the insulinoma is a neoplasm with a wide range of therapeutic and diagnostic solutions, thanks to the progress that has been made in recent years. Although there are many difficulties on a diagnostic path of the insulinoma, new solutions and appropriate aproach make this process easier. Nevertheless, doctor’s diagnostic vigilance is essential, because consideration in the differential diagnosis the insulinoma is an essential step and without this step any further actions can be taken.

The Role of Glucagon-Like Peptide 1 Receptor PET/CT With Ga-68-NODAGA-exendin in Localising an Insulinoma: Lessons From a Clinical Case

We present a clinical case highlighting the diagnostic challenges in a patient with an insulinoma. A 57-year-old lady initially presented with sweating on waking. Investigation documented a fasting blood glucose of 2 mmol/L (3.9-5.4) and the presence of anti-endomysial antibodies. On the basis of a diagnosis of Coeliac disease, the patient was commenced on a gluten free diet with apparent resolution of symptoms for 9 years. Subsequently, she re-presented with recurrent episodes of confusion which resolved with a ‘sugary’ drink. Consequently, she underwent a prolonged supervised fast: glucose 1.9 mmol/L (neuroglycopaenic symptoms), insulin 76 pmol/L (<20), c-peptide 763 nmol/L (<200) and β-hydroxybutyrate (BHB) 131 μmol/L (<2700). A diagnosis of endogenous hyperinsulinaemic hypoglycaemia resulted in radiological investigation (CT thorax/ abdomen/pelvis, MRI pancreas and endoscopic ultrasound [EUS] of pancreas) with no tumor identified. Due to persisting symptoms, in addition to dietary changes, diazoxide and octreotide were commenced. She was referred for a second opinion where a repeat 72-hour fast (at the time of hypoglycaemia symptoms) showed: glucose 2.3 mmol/L, Insulin 51 pmol/L, C-Peptide 513 pmol/L, BHB 1580 μmol/L and proinsulin 31 pmol/L (<10). Insulin antibody and sulphonylurea screens were negative. Her symptoms resolved after carbohydrate ingestion. Further imaging including a Ga-68-DOTATATE PET/CT, selective arterial calcium stimulation and hepatic venous sampling failed to localise an insulinoma. Despite pharmacological treatment hypoglycaemia continued to impede the patient’s quality of life and both octreotide and diazoxide were stopped due to side effects and minimal benefit. A glucagon-like peptide 1 receptor (GLP-1R) PET/CT scan with Ga-68-NODAGA-exendin-4 was performed and revealed uptake in a lesion in the ventral pancreatic body, suggestive of an insulinoma. A further EUS showed a corresponding 10 mm calcified area in the pancreatic body. The surgeon was unable to identify the tumor intra-operatively (macroscopically and ultrasound guided) and therefore performed a distal pancreatectomy which encompassed a 13 mm tumor. Histopathology demonstrated a 13 mm well differentiated, Grade 1 pancreatic neuroendocrine tumor (Ki67 1%) staining positively for AE1/AE3, synaptophysin, chromogranin and insulin (GLP-1R and pro-insulin staining awaited). Post-operatively, there was complete resolution of hypoglycaemia. In summary the learning points are the 9-year interval between initial presentation and confirmation of the diagnosis and the challenge of tumor localisation. There is no published evidence about gluten free diets reducing hypoglycaemia in insulinomas, but our patient described symptomatic improvement. GLP-1R are expressed in >90% of insulinomas and this case underlines the utility of GLP-1R PET/CT in insulinoma localisation.

Essentials of Insulinoma Localization with Selective Arterial Calcium Stimulation and Hepatic Venous Sampling.

Insulinomas are the most common functional pancreatic neuroendocrine tumor. Most insulinomas can be localized non-invasively with cross-sectional and nuclear imaging. Selective arterial calcium stimulation and hepatic venous sampling is an effective and safe minimally-invasive procedure for insulinoma localization that may be utilized when non-invasive techniques are inconclusive. The procedure’s technical success and proper interpretation of its results is dependent on the interventional radiologist’s knowledge of normal and variant pancreatic arterial perfusion. Accurate pre-operative localization aids in successful surgical resection. Technical and anatomic considerations of insulinoma localization with selective arterial calcium stimulation and hepatic venous sampling are reviewed.

Avoiding Pitfalls in Insulinomas by Preoperative Localization with a Dual Imaging Approach

Insulinomas are rare endocrine malignancies of the pancreas that require surgical resection but can be difficult to localize preoperatively. We sought to review and improve the accuracy of preoperative localization techniques at our institution. We retrospectively reviewed all insulinomas that underwent resection at our institution between 1998 and 2016. Localization techniques include selective arterial calcium stimulation (CaStim), CT, MRI, angiography, and somatostatin receptor scintigraphy. Thirty-eight patients had pathologically proven insulinomas on surgical resection. Localization accuracies of CaStim, CT, and MRI were 89 per cent (31/35), 67 per cent (22/33), and 46 per cent (11/24), respectively. When compared with CT alone and CaStim alone, the combination of these two modalities resulted in 100 per cent preoperative localization (30/30), whereas the use of CaStim alone resulted in 80 per cent (4/5) localization and the use of CT alone resulted in 66 per cent (2/3) localization. Four of our patients had both negative CT and MRI. Among these patients, CaStim was 100 per cent localizing and the only positive modality for these patients. These data confirm that CaStim is accurate in preoperatively identifying single and multiple insulinomas; and when combined with CT, this accuracy is increased to 100 per cent. Based on these data, we propose that a dual imaging approach is a superior means of preoperative localization.

Selective arterial calcium stimulation test in two cases with occult insulinoma

Selective arterial calcium stimulation test in two cases with occult insulinoma

SUN-319 Failure Of Pasireotide To Control Hypoglycemia In A Men-1 Patient With Metastatic Insulinoma

Background: Pasireotide appears to be a promising therapeutic approach to refractory hyperinsulinemic hypoglycemia, since hyperglycemia is a frequent side effect when used in the treatment of other neuroendocrine diseases. Clinical case: A 39-year-old woman with MEN1 and severe hypoglycemic episodes was diagnosed with a 5x4 cm lesion in the pancreatic tail in 1999 compatible with insulinoma. The tumor was successfully removed and pathology report described an encapsulated lesion with free margins and low mitotic index. After surgery she became asymptomatic and was regularly followed-up. She started to gradually gain weight from 2004 to 2015, achieving a BMI of 41 kg/m² and decided to undergo a bariatric surgery at another center in 2016. She underwent a gastric bypass and her liver was randomly biopsied. Surprisingly, biopsy revealed a grade I NET. Hypoglycemic symptoms recurred, but she didn't report them immediately, attributing it to the bariatric procedure. An abdominal CT was then performed and showed multiple contrast-enhancing lesions in the pancreatic head, body and tail ranging 0.5-0.8 cm in size, as well as randomly distributed hepatic lesions. A selective arterial calcium stimulation test was performed and identified that both the pancreatic and hepatic lesions were functioning. Short-acting octreotide was prescribed, with worsening of hypoglycemic episodes. Diazoxide was poorly effective and had multiple side effects. Other therapies were considered but due to their toxicity profile, we opted to test pasireotide. After informed consent, a flash glucose monitoring sensor (FreeStyle Libre) was implanted 4 days before starting the drug. In this pretreatment period, her mean glucose was 83 mg/dl. Pasireotide 0.6 mg twice daily was started and she wore the sensor for 10 days. While on treatment her mean glucose was 85 mg/dl. The average 14-day glucose level (including both pretreatment and treatment periods) was 84 mg/dl, the percent of time between 70-140 mg/dl (target range) was 41%, above target 11% and below target 48%. The number of hypoglycemic events was 69 with an average duration of 143 minutes. Although mean glucose levels did not differ during treatment, the patient agreed to undergo another course of treatment, and a new sensor was implanted. In this phase, the patient became progressively symptomatic. This full 14-day treatment period presented an average glucose of 66 mg/dl, the percent of time in range was 28%, above target 6% and below target 66%. The number of hypoglycemic events was 75 with an average duration of 182 minutes. She discontinued the drug after noticing more frequent and severe crises. Conclusion: In contrast to scarce published evidence favoring treatment success, this is the first report of failure to control hypoglycemia in metastatic insulinoma with pasireotide, suggesting that different tumor characteristics may be responsible for adequate response.

MON-328 Twenty-Year Follow-Up of a Patient with a Novel MEN1 Gene Mutation

Background: The multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare autosomal dominant inherited tumor syndrome. Mutations in the MEN1 gene are detectable in approximately 70-90% of kindreds with classic MEN1 syndrome (1). We present the case of a patient with a novel MEN1 gene mutation. Clinical Case: A 41 year old Caucasian male with a diagnosis of MEN1 syndrome has been followed up in our clinic for 20 years. At the age of 21, he had two parathyroid glands resection for hypercalcemia which revealed an adenoma of the right superior parathyroid gland. He had one more parathyroid gland resected 6 months later for persistent hypercalcemia. Around that time, he also had appendectomy for suspected appendicitis and the pathology results showed a carcinoid tumor of the appendix. At the age of 33, he underwent total parathyroidectomy, thymectomy, and auto transplantation of half parathyroid gland in the left forearm for recurrent hypercalcemia. At the age of 39, he developed frequent hypoglycemic episodes with symptoms including confusion. Serum glucose levels of 20-30 mg/dL were documented during the episodes. A 72 hours fasting test showed a plasma glucose level of 53 mg/dL, with insulin level of 25.6 mU/L, proinsulin level of 5.2 pmol/L, C-peptide level of 5 ng/mL and low beta- hydroxybutyrate level. In response to 1 mg glucagon intravenous injection, plasma glucose level improved by 83 mg/dL in 30 minutes. He then had selective arterial calcium stimulation test and the results showed the insulin peak rising after stimulation in the splenic artery suggested that the lesion was in the body and tail of the pancreas. He had partial pancreatectomy for insulinoma, however, the pathology results were consistent with vasoactive intestinal polypeptide- producing tumor (VIPoma) rather than insulinoma. The serum tests also supported a diagnosis of VIPoma: the VIP levels were 96.3 pg/mL preoperatively and 65 pg/mL postoperatively. Notably, he had intermittent abdominal pain after food intake and chronic watery diarrhea 5-7 times a day before pancreatectomy, which resolved after the surgery. The patient underwent genetic screening for MEN1 mutations which revealed the presence of a novel germline deletion mutation in exon 8 (1078delC), resulting in frame shifting of its coded menin protein (Arg360fsX13). Conclusion: We describe a novel MEN1 gene mutation (1078delC) in a patient with typical clinical manifestations of MEN1 syndrome including parathyroid adenomas, appendix carcinoid tumor, VIPoma, and insulinoma. The concurrence of pancreatic VIPoma and insulinoma or the existence of a pancreatic neuroendocrine tumor co-producing insulin and VIP in MEN1 patients has not been reported previously. Reference: (1) Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017;24:T119-T134.

Selective Arterial Calcium Stimulation with Hepatic Venous Sampling in Patients with Recurrent Endogenous Hyperinsulinemic Hypoglycemia and Metastatic Insulinoma: Evaluation in Five Patients

Selective arterial calcium stimulation (SACST) with hepatic venous sampling was performed in 5 patients (3 female, 2 male; age range, 53–73 y) with recurrent endogenous hyperinsulinemic hypoglycemia caused by metastatic insulinoma between January 2004 and December 2014. The biochemical results of SACST confirmed functional hepatic metastases alone (n = 3), peripancreatic lymph-node and hepatic metastases (n = 1), and occult insulinoma in the pancreatic bed (n = 1), thereby helping to guide management. SACST may be useful to determine the extent of functional metastatic insulinoma, particularly within the liver, and may provide clinicians with additional information to help guide the multidisciplinary management of patients with recurrent endogenous hyperinsulinemic hypoglycemia.

68Ga-DOTATATE PET/CT Can Be an Alternative Imaging Method in Insulinoma Patients

Insulinomas are the most common cause of hypoglycemia, resulting from endogenous hyperinsulinism. The diagnosis of insulinoma is established by demonstrating inappropriately high serum insulin concentrations during a spontaneous or induced episode of hypoglycemia. Most insulinomas are islet-cell tumors. They are often small (<2 cm), benign, and difficult to localize with current imaging techniques. Insulinomas can be detected using either noninvasive procedures (e.g., transabdominal ultrasonography, spiral CT, MRI, 111In-pentetreotide imaging, and 18F-l-dihydroxyphenylalanine PET) or invasive procedures (e.g., endoscopic ultrasonography) or a selective arterial calcium stimulation test with hepatic venous sampling. Methods: We performed 68Ga-DOTATATE PET/CT on 3 patients with insulinoma. Results: All patients' insulinomas were shown clearly with 68Ga-DOTATATE PET/CT. Conclusion:68Ga-DOTATATE PET/CT imaging may be a useful noninvasive imaging technique to localize insulinomas preoperatively.