Occult Insulinoma Research Articles

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.

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.

Occult insulinoma after oesophagectomy for oesophageal cancer-diagnostic challenges

Hypoglycaemia in the post-operative period is mainly iatrogenic (related to anti-hyperglycaemic drugs), but can be explained by an endogenous hyperinsulinemic state. In the context of previous gastrointestinal surgery, a form of dumping syndrome can mask hypoglycaemia from an underlying cause, such as an insulinoma. The authors present a clinical case of a male patient who underwent oesophageal surgery for an oesophago-gastric junction adenocarcinoma and developed hypoglycaemic symptoms in the post-operative period, caused by an undiagnosed insulinoma. This case report portraits the diagnostic investigation of a hypoglycaemia state in the post-operative period, narrowing to the workup of an endogenous hyperinsulinemic hypoglycaemia and provides a summary of insulinoma’s treatment. An insulinoma should always be considered in a patient with endogenous hyperinsulinemic hypoglycaemia, even with a history of oesophago-gastric surgery.

Glucagon-like Peptide-1 Receptor as Emerging Target: Will It Make It to the Clinic?

The glucagon-like peptide-1 receptor (GLP-1R) is an emerging target due to its high expression in benign insulinomas as well as in islet cell hypertrophia/hyperplasia (nesidioblastosis) and pancreatic β-cells. In 2008, occult insulinomas were localized for the first time in men using the metabolically stable radiolabeled glucagon-like peptide-1 (GLP-1) agonist [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 (111In-DTPA-exendin-4). Afterward, several radiopharmaceuticals for GLP-1R PET/CT imaging were synthesized and evaluated, for example, [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]-exendin-4 (68Ga-DOTA-exendin-4), [Cys40(MAL-NOTA-68Ga)NH2]-exendin-4 (68Ga-NOTA-exendin-4), and [Lys40(NODAGA-68Ga)NH2]-exendin-4 (68Ga-NODAGA-exendin-4). Several prospective comparison studies provided evidence that GLP-1R PET/CT is significantly more sensitive than contrast-enhanced MRI (ceMRI), contrast-enhanced CT (ceCT), GLP-1R SPECT/CT, somatostatin receptor PET/CT, and SPECT/CT in the detection of benign insulinomas, and insulinomas in the context of multiple endocrine neoplasia type 1. As a result, the European Neuroendocrine Tumor Society guidelines recommend GLP-1R imaging or selective intraarterial calcium stimulation and venous sampling (ASVS) in patients for whom there is a clinical suspicion of having an insulinoma but who have a negative ceMRI/ceCT or negative endoscopic ultrasound. Furthermore, there is growing evidence that GLP-1R PET/CT can visualize and localize adult nesidioblastosis. This is clinically relevant as the distinction between focal and diffuse nesidioblastosis is critical in directing a therapeutic strategy in these patients. Prospective studies have proven the clinical relevance of GLP-1R imaging as it is often the only imaging modality able to localize the insulinoma or nesidioblastosis. It is therefore likely that this noninvasive imaging modality will replace the invasive localization of insulinomas using ASVS. More experimental indications for GLP-1R imaging include the diagnosis of an insulinoma/nesidioblastosis in patients with postprandial hypoglycemia after bariatric bypass surgery and monitoring β-cells in patients with brittle type 1 diabetes after islet-cell transplantation. We believe that these indications and possibly future indications will bring GLP-1R imaging to the clinic.

Insulinoma of Pancreatic Head Localized by Intra-Arterial Calcium Stimulation with Hepatic Venous Sampling

Hypoglycemia is a common medical emergency. Insulinoma, a rare pancreatic endocrine tumour is the most common cause of hypoglycemia in patients without systemic illness. Most insulinomas are small, solitary and benign, which can be treated effectively by surgical removal of the tumour. Diagnosis is based on clinical features, laboratory tests and radiological investigation to localize the tumour. However, small size of this tumour leads to difficulty in localization of the disease, especially in occult insulinoma. Intra-arterial calcium stimulation with hepatic venous sampling can be utilised for preoperative localization of the tumour. We hereby present a case of a 33-year-old woman presenting with history of recurrent hypoglycemic symptoms and morbid obesity. A thorough history, clinical examination and laboratory investigation including prolonged fasting test were conducted and diagnosis of insulinoma was made. Intra-arterial calcium stimulation with hepatic venous sampling was carried out and revealed localization of insulinoma at pancreatic head.
 Bangladesh Journal of Medical Science Vol.20(1) 2021 p.216-219

Superior Diagnostic Performance of the GLP-1 Receptor Agonist [Lys40(AhxHYNIC-[99mTc]/EDDA)NH2]-Exendin-4 over Conventional Imaging Modalities for Localization of Insulinoma.

Insulinomas are the most common functioning neuroendocrine neoplasms of the pancreas, typically diagnosed due to characteristic symptoms. In the vast majority, the treatment is surgical and curative, requiring accurate localization of the tumour; conventional imaging, including somatostatin receptor molecular imaging, is negative in up to 10% of cases. Recently, labelled glucagon-like peptide receptor (GLP-1R) analogues were introduced as a sensitive diagnostic method for localization of insulinomas. The aim of this study was to assess the diagnostic accuracy of a Tc-99m-labelled GLP-1R agonist [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 for localization of occult insulinoma. Eight patients (all females; age range 35-75years) with biochemically proven insulinoma and with negative or inconclusive conventional imaging (consisting of somatostatin receptor scintigraphy, computed tomography, endoscopic ultrasound and magnetic resonance imaging) were enrolled. Whole-body single-photon emission tomography/computed tomography (SPECT/CT) imaging was performed 4h post-injection of 740MBq of [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4. Surgical treatment was performed based on imaging findings. Histology of the removed lesions and biochemical and clinical symptom resolution was considered as the gold standard for analysis of the imaging results. Focal uptake of [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 was found in all patients, leading to successful removal of the offending lesion and complete biochemical and symptomatic resolution. Histological analysis confirmed insulinoma in all included patients. [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 SPECT/CT appears to be an excellent molecular imaging method for preoperative localization of an occult insulinoma, surpassing conventional imaging methods. If routinely available, it could be considered as a method of choice due to its favorable combination of imaging characteristics.

Selective arterial calcium stimulation test in two cases with occult insulinoma

Selective arterial calcium stimulation test in two cases with occult insulinoma

Hypoglycemia Controlled by Prednisone in an Occult Insulinoma or a Nesidioblastosis

Insulinoma is a pancreatic endocrine tumor lower in size than 20 mm in 80% of the cases and his treatment is chirurgical. However, in certain circumstances such as an occult location or circumstances of metastases, medical treatment is called for. Observation: A 29 years old patient with no specific pathological antecedents has presented severe hypoglycemia mainly in the morning. A patient was in a generally good condition. The fasting test revealed an inappropriate secretion of insulin at a venous glycemia of 0.35 g/l; which was corroborated by Turner index and altered glucose insulin index that we calculated. Moreover, the 8 h cortisolemia was normal at 90.13 ng/l, the TSH was normal at 1.44 μui/l, anti-insulin antibodies were negative at 6.7 U/l; the search of hypoglycemic sulfonamides was negative. Morphologically, she had three pancreatic tomodensitometry these were normal. She also had echo-endoscopy which showed a normal pancreas. The surgical exploration with preoperative echo is advised only after surgeon’s assessment when the technical conditions are not put together. The diagnosis of the occult insulinoma or of nesidioblastosis was retained. The medical treatment was retained. Due to the unavailability of diazoxide in our pharmacies and the high cost of analogs of somatostatine, she was provided with prednisone 0.5 mg/kg/24h which was 40 mg/day after common agreement. The evolution was favorable. Conclusion: It should be noticed that medical treatment can be suggested if insulinoma is not localized. This observation proves that the localization of the insulinoma can be unsuccessful. It should also be noticed that our experience is the fourth described in literature, where hypoglycemia in insulinomas is controlled by prednisone.

Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid.

SummaryInsulin autoimmune syndrome (IAS), or Hirata disease, is a rare hypoglycaemic disorder caused by the presence of high titer of insulin autoantibodies (IAA) in patients without previous exposure to exogenous insulin. Even though its pathogenesis is not fully understood, striking evidences link IAS to previous exposure to sulphydryl-containing medications, like alpha-lipoic acid, a widely used nutritional supplement. Although challenging, a careful differential diagnosis from other causes of hyperinsulinaemic hypoglycaemia (such as insulinoma) is mandatory, since these conditions require different therapeutic approaches. In the present study, we report a 35-year-old woman originally from Sri Lanka who was referred to our University Hospital on suspicion of occult insulinoma. Her medical history was positive for endometriosis, treated with estroprogestins and alpha-lipoic acid. The latter supplement was begun 2 weeks before the first hypoglycaemic episode. Our tests confirmed the presence of hypoglycaemia associated with high insulin and C-peptide concentrations. When insulin concentrations were compared using different assays, the results were significantly different. Moreover, insulin values significantly decreased after precipitation with polyethylene glycol. An assay for IAA proved positive (530 U/mL). A genetic analysis revealed the presence of HLA-DRB1*04,15, an immunogenetic determinant associated with IAS. On the basis of clinical data we avoided a first-line approach with immunosuppressive treatments, and the patient was advised to modify her diet, with the introduction of frequent low-caloric meals. During follow-up evaluations, glucose levels (registered trough a flash glucose monitoring system) resulted progressively more stable. IAA titer progressively decreased, being undetectable by the fifteenth month, thus indicating the remission of the IAS.Learning points:Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinaemic hypoglycaemia, whose prevalence is higher in East Asian populations due to the higher prevalence of specific immunogenetic determinants. Nevertheless, an increasing number of IAS cases is being reported worldwide, due to the wide diffusion of medications such as alpha-lipoic acid.Differential diagnosis of IAS from other causes of hyperinsulinemic hypoglycaemia is challenging. Even though many tests can be suggestive of IAS, the gold standard remains the detection of IAAs, despite that dedicated commercial kits are not widely available.The therapeutic approach to IAS is problematic. As a matter of fact IAS is often a self-remitting disease, but sometimes needs aggressive immunosuppression. The benefits and risks of any therapeutic choice should be carefully weighted and tailored on the single patient.

(68)Ga-exendin-4 PET-CT for the localization of occult insulinomas: a prospective cohort study

Objective: To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with (68)Ga-exendin-4. Methods: In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. (68)Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated. Results: A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive (68)Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of (68)Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7. Conclusion: (68)Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.

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.

Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma

Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Histologically, diffuse islet hyperplasia with increased number and size of islet cells is present and confirms the diagnosis. Differentiating NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy is the procedure of choice; however, recurrence of symptoms, although less debilitating, occurs commonly. Medical management with diazoxide, verapamil and octreotide can be used for persistent symptoms. Ultimately, near-total or total pancreatectomy may be necessary. We report a case of a 67-year-old male with hypoglycemia in whom preoperative workup, including computerized tomography abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH instead.

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma.

IntroductionThe aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma.Materials and MethodsForty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions.ResultsPositive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient).Conclusions99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma.

LOCALIZATION OF PANCREATIC INSULINOMAS WITH ARTERIAL STIMULATION BY CALCIUM AND HEPATIC VENOUS SAMPLING - PRESENTATION OF A SINGLE CENTRE EXPERIENCE.

Arterial stimulation and venous sampling (ASVS) is the most sensitive diagnostic method for occult insulinoma localization. We present our experience with this method and modifications used that proved to ensure greater safety and sensitivity with this rare pathology. Relationship between tumour size and changes in peak insulin values and release curves were also tested. Six consecutive patients with biochemically established diagnosis of endogenous hyperinsulinism underwent preoperative non-invasive diagnostic tests with sensitivities calculated and compared for all methods. Certain modifications were used in ASVS procedure that included hepatic vein catheterization, order of arterial stimulation, time intervals between each stimulation, diagnostic insulin gradient level and the time frame for diagnostic rise of insulin. Peak insulin values and insulin gradients were compared with tumour size in each patient. In all patients, calcium stimulation accurately localized the insulinoma, with higher sensitivity than any other method. A more than 4-fold increase in insulin level was observed in all patients, after injection into the tumour feeding artery, while 2 to 4-fold increase was observed in the tumour neighbouring areas. Tumour size showed an inversely proportional correlation to peak insulin values in each artery that correctly located the tumour. ASVS presents the most accurate and safe method for localization of occult insulinomas. A four-fold insulin gradient can be used as a limit for positive preoperative localization in order to secure a higher specificity.

Preoperative localization of an insulinoma: selective arterial calcium stimulation test performance

Preoperative localization of an insulinoma is recommended to improve the cure rate, but non-invasive procedures can fail to detect the tumour. The objective of the study was to assess the performance of a selective arterial calcium stimulation test in the preoperative localization of insulinomas that were not detected by conventional imaging procedures. We conducted a monocenter retrospective case review of 13 patients who had endogenous hyperinsulinism and were treated between 1994 and 2013. Patients were selected on the basis of negative or doubtful non-invasive preoperative imaging. A selective arterial calcium stimulation test was performed by pancreatic and hepatic arteriography with selective intra-arterial calcium stimulation and hepatic venous sampling in order to obtain the plasma insulin measurement. We evaluated the efficacy of the test by comparing the results with an endoscopic ultrasound. Twelve of the 13 patients underwent surgery, and the presence of an insulinoma was proven in 11 patients by pathological analysis of the tumour. An endoscopic ultrasound was consistent with surgery in 71.4 % of cases, while selective arterial calcium stimulation was consistent with surgery in 90.9 % and allowed detection of an insulinoma in two additional patients with a negative endoscopic ultrasound. One false-negative and one false-positive arterial calcium test were observed. No adverse events were recorded except transient skin flush following calcium injection in one patient. The selective arterial calcium stimulation test is a sensitive diagnostic procedure for localizing insulinomas and may be considered when non-invasive radiological imaging does not allow the detection of an occult insulinoma.

Impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation with hepatic venous sampling for preoperative localization of occult insulinoma

To determine the impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation (SACST) with hepatic venous sampling for preoperative localization of occult insulinoma. An institutional review board-approved retrospective review was undertaken of 42 patients with surgically confirmed, occult insulinoma who underwent SACST from January 1996 to March 2014. Location of the insulinoma was predicted initially based on the biochemical results of SACST alone according to Doppman's criteria. Pancreatic arteriograms were reviewed blinded to the biochemical results and the regional perfusion of each artery assessed. The anatomic and perfusion data were combined with the biochemical results to make a second prediction and compared with the surgical findings. The biochemical results were positive in 1, 2, and 3 arterial distributions in 73.8%, 21.4%, and 4.8% of patients, respectively. The celiac trunk and superior mesenteric artery (SMA) anatomy were aberrant in 38.1% and 35.7% of patients, respectively. Clinically significant variations included dorsal pancreatic artery replaced to SMA (21.4%) and celiac stenosis (4.8%). Significant variation and overlap in regional pancreatic perfusion was observed, particularly for the SMA. Sensitivity for insulinoma localization was 54.8% (diagnostic arteriography), 73.8% (biochemical data), 88.1% (biochemical, anatomic, perfusion data), and 92.8% (arteriographic, biochemical, anatomic, perfusion data). Careful review of the pancreatic arterial anatomy and regional perfusion is critical for correct interpretation of the biochemical results of SACST and improves the sensitivity of localization for occult insulinoma, particularly in the presence of pancreatic arterial variants or overlap in regional perfusion.

GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs)

For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging techniques is usually mandatory for primary tumour visualisation, tumour staging and evaluation of treatment. In specific cases, as in patients with occult insulinomas, sampling procedures can provide a clue as to where to localise the insulin-hypersecreting pancreatic NETs. Recent developments in these fields have led to an increase in the detection rate of primary GEP-NETs and their metastatic deposits. Radiopharmaceuticals targeted at specific tumour cell properties and processes can be used to provide sensitive and specific whole-body imaging. Functional imaging also allows for patient selection for receptor-based therapies and prediction of the efficacy of such therapies. Positron emission tomography/computed tomography (CT) and single-photon emission CT/CT are used to map functional images with anatomical localisations. As a result, tumour imaging and tumour follow-up strategies can be optimised for every individual GEP-NET patient. In some cases, functional imaging might give indications with regard to future tumour behaviour and prognosis.

Educational Exhibit Abstract No. 386 - Calcium arterial stimulation venous sampling for preoperative localization of occult insulinomas

Learning Objectives (1) To review the clinical features, diagnosis, and treatment of insulinomas, (2) to discuss the indications and advantages of intra-arterial calcium-stimulated venous sampling (ASVS) vs. portal venous sampling and imaging for preoperative diagnosis of occult insulinomas, (3) to discuss the physiologic rationale of ASVS, technique, and result interpretation. Background Insulinomas cause symptomatic hypoglycemia and are the most common islet cell tumors. Surgical resection is curative. Preoperative localization of an insulinoma is a prerequisite of successful surgical resection. Cross-sectional imaging modalities unreliably detect insulinomas less than 2 cm in size. ASVS is a highly sensitive test for localizing such occult insulinomas. Administration of calcium gluconate into the arterial supply of normal beta cells causes insulin release. The insulin surge from beta cells of an insulinoma is much greater allowing for tumor localization based on site of arterial injection. In the setting of multifocal pancreatic lesions, ASVS can also be used to identify the region that is hormonally most active prior to the resection. Clinical Findings/Procedure Details ASVS is performed in a fasting state. Arteries supplying the pancreas are selected and calcium gluconate is injected. Blood samples are obtained from hepatic veins simultaneously with each injection and evaluated for insulin levels. Location of the insulinoma is determined based on increase in the hepatic venous insulin levels corresponding to the pancreatic arterial territory stimulated. We will discuss the diagnostic algorithm, illustrate the ASVS technique in detail, and interpret the test results. We will also explain the physiologic rationale of the test, angiographic findings of insulinoma and potential use of cone beam CT scan in optimizing localization and identification. Conclusion and/or Teaching Points ASVS is the most accurate method to localize occult insulinomas preoperatively. Familiarity with this technique has the potential to improve clinical outcomes after surgical resection.

A case of occult insulinoma localized by pancreatic dynamic enhanced spiral CT

Insulinomas are the most common category of pancreatic endocrine tumors, with an annual incidence of 1-4 cases per million people. Most are intrapancreatic, benign and solitary. Therefore, they have an excellent prognosis after surgical resection. However, the localization diagnosis of insulinomas still poses a challenge to surgeons and radiologists. In this case, the tumor was occult and could not be found by either abdominal enhanced spiral computed tomography (CT) or ultrasonography. Therefore, we tried a new method of CT scanning and localized the tumor.

Peritoneal Dialysis Masking Symptoms of an Insulinoma Uncovered During the Perioperative Period: A Case Report

A 61-year-old male with a chronic history of renal insufficiency treated with peritoneal dialysis (PD) was discovered to be asymptomatic for an occult insulinoma after peripheral revascularization. The patient's near continuous provision of glucose in the PD fluid acted to conceal symptoms of an insulinoma which was revealed when PD was interrupted. The patient had delayed emergence from general anesthesia resolving with glucose administration, precipitating insulinoma work up.