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BACKGROUND: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon-like peptide-1 receptors enabling positron emission tomography-computed tomography imaging with its radiolabelled analogue; 68 Ga-DOTA-Exendin-4 (Exendin). AIM: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post-gastric bypass hypoglycaemia (PGBH). METHODS: This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report. RESULTS: Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH. CONCLUSION: In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH.

Introduction Inappropriate insulin secretion could be due to several diseases. Nesidioblastosis is characterized by diffuse hyperplasia of pancreatic beta cells, causing organic hypoglycemia. No pancreatic lesions are found on the imaging of patients with this condition. Diazoxide is used as a first-line treatment but can be poorly tolerated because of its side effects, and therapeutic failure is possible. Somatostatin analogues have limited efficacy because of their poor affinity to somatostatin (SST) receptors. Pasireotide is a somatostatin analogue with a much higher affinity to SST receptors, especially SST5, and it could thus be more efficient for treating nesidioblastosis-related hypoglycemia. Observation A 56 years-old diabetic woman had symptoms of hypoglycemia, persistent after treatment's withdrawal. A fasting test authentify an organic hypoglycemia, at 34mg/dL, a plasma insulin level at 6mUI/L above the 5 mU/L threshold, a C-peptide level at 1.9 ng/mL above the threshold of 0.6, and an insulin/C-peptide ratio 0.066, below the threshold of 1. No lesions were found on CT-scan or endoscopic ultrasound. Somatostatin receptor scintigraphy was also negative. Diazoxide and octreotide failed to improve the recurrence of hypoglycemia episodes. With pasireotide LAR, hypoglycemia disappeared and glycemia increased. Hyperglycemia was controlled with sitagliptin. The patient has now been treated with pasireotide LAR for two years, with no more episode of hypoglycemia until now. Discussion We present the first case of nesidioblastosis treatment with pasireotide LAR, with success. Patients diagnosed with nesidioblastosis and diazoxide-resistant hypoglycemia, or who experience difficulties with other treatments, could use pasireotide LAR in conjunction with glycemia monitoring, particularly if they are diabetic.

Octreotide may be useful in noninsulinoma pancreatogenous hypoglycemia syndrome with nesidioblastosis patients who was on hemodialysis. Continuous octreotide subcutaneous infusion can reduce side‐effects and stabilize plasma glucose levels.

A 3‐month‐old male intact Shiba Inu dog was evaluated for a seizure disorder initially deemed idiopathic in origin. Seizure frequency remained unchanged despite therapeutic serum phenobarbital concentration and use of levetiracetam. The dog was documented to be markedly hypoglycemic during a seizure episode on reevaluation at 6 months of age. Serum insulin concentrations during hypoglycemia were 41 U/μL (reference range, 10‐29 U/μL). The dog was transitioned to 4 times per day feeding, diazoxide was started at 3.5 mg/kg PO q8h, and antiepileptic drugs were discontinued. No clinically relevant abnormalities were identified on bicavitary arterial and venous phase contrast computed tomographic imaging. The dog remained seizure‐free and clinically normal at 3 years of age while receiving 5.5 mg/kg diazoxide PO q12h and twice daily feeding. Seizures later occurred approximately twice per year and after exertion, with or without vomiting of a diazoxide dose. Blood glucose curves and interstitial glucose monitoring were used to titrate diazoxide dose and dosing interval. Congenital hyperinsulinism is well recognized in people but has not been reported in veterinary medicine.

Aims/Introduction We aimed to investigate the nationwide incidence, treatment details and outcomes of patients with endogenous hyperinsulinemic hypoglycemia (EHH), including those with transient/persistent congenital hyperinsulinism (CHI), insulinoma, non‐insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata’s disease) in Japan. Materials and Methods A nationwide, questionnaire‐based survey was carried out to determine the number of patients with EHH who were treated for hypoglycemia or hypoglycemia‐related complications in 2017−2018. The questionnaires were sent to all hospitals in Japan with >300 beds, and with pediatric and/or adult clinics likely managing EHH patients. The secondary questionnaires were sent to obtain the patients’ date of birth, sex, age at onset, treatment details and post‐treatment outcomes. Results A total of 447 patients with CHI (197 transient CHI, 225 persistent CHI and 25, unknown histology), 205 with insulinoma (118 benign, 18 malignant and 69 unknown subtype), 111 with non‐insulinoma pancreatogenous hypoglycemia syndrome (33 post‐gastric surgery HH, 57 postprandial HH, 10 nesidioblastosis and 11 unknown subtype) and 22 with insulin autoimmune syndrome were identified. Novel findings included: (i) marked improvement in the prognosis of persistent CHI over the past 10 years; (ii) male dominance in the incidence of transient CHI; (iii) non‐insulinoma pancreatogenous hypoglycemia syndrome emerging as the second most common form of EHH in adults; (iv) frequent association of diabetes mellitus with insulin autoimmune syndrome; and (v) frequent post‐treatment residual hypoglycemia and impaired quality of life. Conclusions The first nationwide, all age group survey of EHH showed the current status of each type of EHH disorder and the unmet needs of the patients., The first nationwide, all age‐group survey of endogenous hyperinsulinemic hypoglycemia showed the current status of each type of endogenous hyperinsulinemic hypoglycemia disorder and the unmet needs of the patients.

Nesidioblastosis is an uncommon cause of organic persistent hyperinsulinemic hypoglycemia in adults. We report a case of adult-onset diffuse β-cell nesidioblastosis in a 49-year-old woman who was status-post Roux-en-Y gastric bypass and distal pancreatectomy for a well-differentiated pancreatic neuroendocrine tumor. While the neuroendocrine tumor was suspected to be an insulinoma, persistent hypoglycemia postoperatively suggested either incomplete resection or a second pancreatic neoplasm. Completion pancreatectomy revealed islet β-cell hyperplasia and nuclear pleomorphism consistent with β-cell nesidioblastosis. The patient’s blood glucose levels normalized after completion pancreatectomy. While β-cell nesidioblastosis and insulinomas can coexist in the same patient, pathologists should be aware of β-cell nesidioblastosis as a potential cause for hyperinsulinemic hypoglycemia and should exclude it in patients who have not shown definitive clinical response after surgical excision of a pancreatic neuroendocrine tumor.

Fabry’s disease is caused by progressive lysosomal accumulation of neutral glycosphingolipids, primarily globotriaosylceramide. It results from deficiency of the enzyme α-galactosidase A, which is encoded by GLA on the X chromosome. Usually it presents in children as the classic variant, and the cardiac variant is extremely rare. Before labeling as cardiac variant in infants and children we should rule out other causes of the cardiac hypertrophy with left ventricular outflow tract obstruction like metabolic causes, hypertrophic cardiomyopathy in infants, Noonan’s syndrome, and nesidioblastosis.We report a case of cardiac variant of Fabry’s disease in a 2-year-old male child. On evaluation he is found to have cardiac hypertrophy with no other features of Fabry’s disease, with low α galactosidase levels with no other systemic and syndromic features, which is an extremely rare presentation.

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.

Context Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Case description A 63-year-old white woman presented at our institution on April 2017 with a history of distal spleno-pancreatectomy for well-differentiated insulinoma in 2013. Hypoglycemic events did not resolve after surgery, and residual nesidioblastosis near the pancreatic resection margins was identified. Hypoglycemic episodes increased in frequency and severity despite high-dose diazoxide (DZX) therapy. On April 2016, octreotide was introduced but soon discontinued for inefficacy. When the patient arrived at our attention, add-on pasireotide was started and glucose levels monitored by subcutaneous sensor. Compared with DZX, 225 mg/d alone, sensor glucose during pasireotide + DZX 75 mg/d showed occurrence of severe hypoglycemia. Pasireotide was discontinued, and the instrumental workup (68Ga-DOTATOC CT/positron emission tomography, 99mTc-nanocolloid scintigraphy and echo-endoscopy + fine-needle aspiration biopsy) identified an insulinoma relapse. Subtotal pancreatectomy was performed without further recurrence of hypoglycemia over 9 months of follow-up. Conclusions Although insulinoma relapses on background nesidioblastosis rarely occur, they should be considered as an alternate diagnosis when medical therapy fails to prevent hypoglycemia. Further studies are warranted to test whether the immunophenotypic signature of nesidioblastosis/insulinoma may provide insights for a tailored use of pasireotide.

INTRODUCCION La nesidioblastosis es una enfermedad poco frecuente en los adultos caracterizada por hiperplasia de los islotes pancreaticos, produciendo hipoglucemia por incremento de la produccion de insulina. Su patogenia es poco conocida. Clinicamente se ha descrito un cuadro de hipoglucemia con valores elevados de insulina y de peptido C sin ninguna lesion tumoral pancreatica detectable. El diagnostico final es histopatologico. CASO CLINICO Mujer de 36 anos que cursa con episodios recurrentes de hipoglucemia sintomatica de predominio posprandial, asociada a elevacion de los valores sanguineos de insulina y peptido C. Los estudios de imagenes (tomografia computarizada trifasica, resonancia magnetica, ecoendoscopia y octreoscan) no mostraron lesiones compatibles con insulinoma. Se le realizo estimulacion intraarterial con calcio, que mostro un incremento de la insulinemia en mas de un segmento pancreatico posestimulacion. La paciente fue sometida a pancreatectomia corporocaudal, cuya evaluacion histopatologica informo de nesidioblastosis. CONCLUSIONES La nesidioblastosis representa menos del 5% de los casos de hipoglucemia hiperinsulinemica en los adultos, por lo que debe considerarse como diagnostico -diferencial en estos pacientes; su diagnostico es dificil y requiere confirmacion histopatologica. BACKGROUND Nesidioblastosis is a rare disease in adults caused by pancreatic islet hyperplasia, producing hypoglycemia due to an increase in insulin production. The pathogenesis is poorly understood, however a clinical picture characterized by hypoglycemia with high levels of insulin and C-peptide without any detectable pancreatic lesion has been described, its final diagnosis is histological. CASE REPORT We report a case of a 36-year-old female patient who presents with recurrent episodes of hypoglycemia symptomatic predominantly postprandial, associated with insulin and C-peptide elevation. Images were made (triphasic computed tomography, magnetic resonance imaging, echoendoscopy and octreoscan), being negative for insulinoma. Subsequent tests included calcium stimulation of the pancreas, revealing marked insulin release in more than one pancreatic segment. The patient was subjected to distal pancreatectomy confirming in the histological study the diagnosis of nesidioblastosis. CONCLUSIONS Nesidioblastosis accounts for less than 5% of the cases of cases of hyperinsulinemic hypoglycemia in adult patients, should be considered as a differential diagnosis in patients with persistent hypoglycemia, the diagnosis is difficult and usually requires histological confirmation.

Prevalence of bariatric surgery is on increasing trend all over the globe due to sustainable weight loss, improvement in quality of life, and comorbidity resolution. Therapies for obesity can be divided broadly into four groups: behavioural (primarily diet and exercise), drugs, devices (intragastric balloon), and surgery. The complications of bariatric surgery include gastrointestinal complications, venous thromboembolism, and nutritional complications. The overall complication rate is low ranging from 0.29% to 0.78% [1], which is similar to most elective abdominal operations like cholecystectomy. The reported common early complications include leak, bleeding, obstruction, venous thromboembolism while the late complications include internal hernias, dumping, nutritional deficiencies, and gastro-oesophageal reflux. In this chapter, we will discuss the common metabolic GI complications specific to each procedure. Hormonal and physiological changes following bariatric surgery are covered in another chapter and therefore, will not be discussed here. The delayed and long-term surgical complications like Internal hernia, obstruction, stenosis etc. will also not be discussed as the focus of the book is on metabolic complications. Additionally, liver complications, nesidioblastosis, and nutritional complications have been discussed in other chapters and will not be discussed.

La hipoglucemia por hiperinsulinismo endógeno suele presentarse en dos situaciones patológicas: la más frecuente es el insulinoma y, en segundo lugar, la nesidioblastosis o síndrome hipoglucémico pancreático no insulinoma. La nesidioblastosis es una causa poco frecuente de hipoglucemia por hiperinsulinismo en adultos. Presentamos el caso de un paciente adulto con cuadros recurrentes de hipoglucemia secundarios a nesidioblastosis.

Introduction: Congenital hyperinsulinism (CHI), or nesidioblastosis, is the most common cause of severe persistent hypoglycemia in neonates. When left untreated, CHI may cause serious brain damage and could eventually even lead to death.1 In case of diffuse hyperinsulinism, when all beta cells are inappropriately over-secreting insulin, a near-total pancreatectomy may be indicated. With the goal of resecting 958 only a small residue of pancreatic tissue between the common bile duct (CBD) and the duodenal wall is left behind.2 To perform an adequate near-total pancreatectomy, the intrapancreatic segment of the CBD has to be safely dissected. Hereby, a feared complication is intraoperative CBD injury, associated with significant morbidity. Intraoperative injury has been reported to occur in up to 16,4 A laparoscopic near-total pancreatecomy is even more technically challenging, especially in the young. Therefore, to date, most near-total pancreatectomies in infants are done by traditional laparotomy. Fluorescence imaging with intravenous administration of indocyanine green (ICG) allows for clear intraoperative observation of the bile duct anatomy, which might ease the technical difficulties inherent to the near-total pancreatectomy, particularly with a laparoscopic approach.5 This video presents a 10-month-old boy, who presented with severe persistent hypoglycemia immediately after birth. Genetic testing was performed and confirmed the diagnosis of diffuse severe CHI based on a pathogenic homozygous ABCC8 mutation. Owing to the severely drug-resistant nature of his CHI, a laparoscopic spleen-preserving distal pancrearectomy was performed at the age of 8 weeks, later followed by a laparoscopic spleen-preserving central pancreatectomy at the age of 7 months. Although after these procedures only one third of the pancreas was left behind, the patient continued to have hypoglycemia despite maximal pharmaceutical treatment with different short- and long-acting somatostatin analogues and a high carbohydrate intake. Therefore, a third near-total pancreatic resection was indicated and was performed at the age of almost 11 months. Materials and Methods: Under general anesthesia, the patient was placed in supine position. A 5 mm trocar was introduced subumbilically with two trocars aside paraumbilically and one trocar positioned in the left flank, more laterally to allow access of the upper right abdomen. First, the stomach was lifted through an earlier placed percutane endoscopic gastrostomy, placed to supply an adequate intake of carbohydrates. After transecting the right gastroepiploic vein and artery, the proximal duodenum was retracted toward the upper right quadrant through a vessel loop exiting next to the most lateral port. Then, the gastroduodenal artery was transected, after placement of clips on the side of the hepatic artery, using the harmonic scalpel. Subsequently, the uncinate process of the pancreas was dissected after the superior mesenteric vein was identified. The pancreatic head was superficially split with harmonic scalpel in such a manner that the CBD with surrounding pancreatic tissue remained intact. Then, 1 mL ICG (0.5 mg/kg) was injected intravenously. After 15 minutes of waiting, the liver appeared as well as the duodenum by drainage through the ampulla of Vater. In between, the CBD was clearly observed. Thereafter, under direct vision of the CBD, the near-total pancreatectomy was continued by dissecting pancreatic tissue from the ventral and left border of the CBD. After the dissection of the pancreatic tissue was completed, the specimen was extracted using an endobag through the subumbilical incision. Results and Conclusions: Approximately 546 minutes and the measured blood loss was 10 mL. There were no perioperative complications and no iatrogenic injury to the CBD occurred. Any bile leakage from the CBD would immediately have been observed by fluorescence imaging, and in this case no leakage was seen during dissection of pancreatic tissue around the CBD. During the postoperative course, there were no surgical complications. The surgical drain was removed after 3 days, as amylase levels remained low. Postoperatively, carbohydrate intake could be reduced, medical treatment with somatostatin analogues was stopped, and the interval between feeding in portions could be extended up to 4 hours without resulting in hypoglycemic episodes. At discharge, just after his first birthday, there were no signs of exocrine pancreatic dysfunction, and glucose levels were acceptable on the current feeding schedule. We conclude that ICG fluorescence imaging may offer a benefit for laparoscopic near-total pancreatectomy in infants for drug-resistant diffuse CHI, as it clearly enhances the observation of the CBD intraoperatively, facilitating a safe and adequate pancreatic tissue dissection with maintenance of the integrity of the intrapancreatic segment of the CBD. No competing financial interests exist. Runtime of video: 4 mins 2 secs

Nesidioblastosis is a very rare adult disorder in the absence of gastrointestinal surgery. Nesidioblastosis is a disorder of the endocrine pancreas causing hyperinsulinemic hypoglycemia. We describe a case of 83 year-old Caucasian male, with a 3-year history of severe refractory hypoglycemia with glucose level below 2.1 mmol/L. Confusion and sleepiness were reported as his neuroglycopenic symptoms. According to his family, his symptoms improved within 30 minutes of drinking orange juice. Hypoglycemia episodes mostly occurred while fasting and post exercise (after playing golf). His work up included low venous plasma glucose levels, high insulin and C-peptide levels that were consistent with an insulinoma. His history is remarkable for chronic kidney disease stage 3, penicillin allergy and atrial fibrillation with loop recorder for cardiac rhythm monitoring, which precluded him from undergoing CT with IV contrast or MRI studies. Abdominal computed tomography with oral contrast did not reveal any lesion. In an attempt to localize the suspected Insulinoma, he had celiac angiogram and portal vein sampling, which were inconclusive. He had a PET scan with dotatate that showed increased amount activity in the uncinate process of the pancreas. He was diagnosed with insulinoma and placed on monthly lanreotide injections, however continued to have severe hypoglycemia episodes. Due to persistent refractory hypoglycemia, patient underwent distal pancreatectomy and splenectomy and the histological findings were consistent with nesidioblastosis. Patient developed hyperglycemia in the post-operative course which was controlled with a carb consistent diet. This case demonstrates that differentiation between insulinoma and nesidioblastosis is very challenging, and in most cases, the diagnosis is made post operatively based on histologic findings.

Background Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a rare syndrome characterized by postprandial hypoglycemia with neuroglycopenic symptoms occurring 1 to 3 h after a meal. Diagnosis can be elusive, as the vast majority of patients have normal fasting blood glucose levels, and onset of hypoglycemic episodes can be a late complication of gastric surgery. Case Report We report the case of a 45-year-old woman presenting to the Emergency Department (ED) with new-onset seizures and hypoglycemia worsened by glucose administration. Surgical history is pertinent for a Roux-en-Y gastric bypass approximately 10 years prior to presentation. Why Should an Emergency Physician Be Aware of This? Although rare, it is important for emergency physicians to be vigilant of this disease process as a traditional treatment approach for hypoglycemia may be detrimental. Although cases of NIPHS have been documented in literature, its presence in emergency medicine-specific literature is seemingly nonexistent. Noninvasive imaging techniques will be normal, and diagnosis is dependent on awareness of this disease entity coupled with a detailed history.

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.

Patient: Male, 32-year-old Final Diagnosis: Nesidioblastosis Symptoms: Hypoglycemia Medication:— Clinical Procedure: Distal pancreatectomy • magnetic resonance image • selective arterial calcium stimulation test with hepatic venous sampling Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Nesidioblastosis is a rare disease that is part of the differential diagnosis of pancreatogenic hyperinsulinemic hypoglycemia (PHH) in patients whose imaging studies do not localize insulinoma. Pancreatic heterotopia is a rare congenital abnormality characterized by pancreatic tissue anatomically separated from the main gland and found in 0.5% of abdominal surgeries. The purpose of this article is to provide a systematic review of the literature on nesidioblastosis in pancreatic ectopic tissue and to describe a case of the co-occurrence of these 2 rare conditions. Case Report: A 32-year-old man presented with adrenergic and neuroglycopenic symptoms, with laboratory-confirmed hyper-insulinemic hypoglycemia. There was no evidence of tumors on abdominal CT scan and MRI. Celiac trunk sampling with a calcium stimulation test was done, which showed an insulin gradient in the gastroduodenal artery. However, the intraoperative ultrasound showed a small nodule located at the pancreatic tail, leading to distal pancreatectomy. The histologic examination showed nesidioblastosis associated with pancreatic heterotopia. The patient remained asymptomatic after distal pancreatectomy. Conclusions: Nesidioblastosis accounts for 0.5%–5% of all cases of PHH, with a histology showing hypertrophy and hyper-plasia of pancreatic islets. Pancreatic heterotopia is a rare congenital anomaly resulting from failure of pancreatic cell migration, and is found as an incidentaloma in imaging or surgeries. Although it is a rare disease, nesidioblastosis should be considered in the investigation of hypoglycemia, even in the rare presentation of nesidioblastosis in patients with pancreatic heterotopy.

Background Congenital hyperinsulinism (CH) is a rare disease, characterized by severe hypoglycemia induced by inappropriate insulin secretion from pancreatic beta-cells in neonate and infant. Hirschsprung’s disease (HD) is also a rare disease in which infants show severe bowel movement disorder. We herein report an extremely rare case of combined CH and HD. Case presentation The patient was a full-term male infant who showed poor feeding, vomiting, and hypotonia with lethargy on the day of birth. He was transferred to tertiary hospital after a laboratory analysis revealed hyperinsulinemic hypoglycemia. The patient showed remarkable abdominal distension without meconium defecation. An abdominal X-ray showed marked dilatation of the large bowel. He was diagnosed with CH (nesidioblastosis) associated with suspected HD. He was initially treated with an intravenous infusion of high-dose glucose with the intermittent injection of glucagon. This was successfully followed by treatment with diazoxide and octreotide (a somatostatin analog). At 8 months of age, HD was confirmed by the acetylcholinesterase staining of a rectal mucosal biopsy specimen, and a transanal pull-through operation was performed to treat HD. At 14 months of age, subtotal pancreatectomy was performed for the treatment of focal CH located in the pancreatic body. His postoperative course over the past 12 years has been uneventful without any neurologic or bowel movement disorders. Conclusions Although it is extremely rare for CH to be associated with HD, associated HD should be considered when a patient with CH presents severe constipation.

Nesidioblastosis is also called hyperinsulinemic hypoglycemia and congenital hyperinsulinism. It is attributed to excessive function of pancreaticbeta cells. The clinical features, diagnosis and aspects of management are discussed.

Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma.Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels (p < 0.0001) and reduction of nocturnal hypoglycemia episodes (p = 0.0002).Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.

Hypoglycemia after Roux-en-Y gastric bypass is a rare and challenging condition. It occurs several months to years after surgery and has been more commonly seen in females. Severe hypoglycemia presents with symptoms of the Whipple’s triad that include signs as perspiration, palpitations, hunger, fatigue, confusion, aggression, tremor, syncope, a low plasma glucose concentration, and resolution of those symptoms after carbohydrate intake. Specific symptoms of hypoglycemia are categorized as autonomic or neuroglycopenic. Autonomic symptoms include anxiety, sweating, tremors, and palpitation. Neuroglycopenic symptoms comprehend confusion, weakness, light-headedness, dizziness, blurred vision, disorientation, and eventually, loss of consciousness, coma, and death.

Severe cases of postprandial hypoglycaemia after bariatric surgery can be a diagnostic and therapeutic challenge. The diagnostic role of 68Ga-DOTA-Exendin-4 PET/CT in postbariatric hypoglycaemia for further treatment decisions is unclear. We present a case of a 50-year-old woman with frequent and severe postprandial hypoglycaemic (≤2.5 mmol/L) episodes starting three years after Roux-Y gastric bypass. Despite strict dietary adherence and several medical therapies, the patient remained severely affected, and 68Ga-DOTA-Exendin-4 PET/CT was performed to exclude atypical presentation of an insulinoma or nesidioblastosis. No pancreatic abnormalities were found, but intensive tracer accumulation in the first and second part of the duodenum was detected, which proved to be hyperplastic Brunner’s glands on histology and were strongly positive for the glucagon-like peptide-1 receptor. This case provides histopathological verification that duodenal 68Ga-DOTA-Exendin-4 uptake is caused by uptake in Brunner’s glands and points to a potential relationship between bariatric surgery and Brunner’s glands.

Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.

espanolIntroduccion: La nesdioblastosis se define como proliferacion de las celulas endocrinas pancreaticas, que comporta alteraciones en su distribucion y diferenciacion. El numero de los islotes de Langerhans es menor de lo normal, encontrandose las celulas endocrinas distribuidas, anarquicamente, por el parenquima pancreatico, en forma de pequenos nidos o cordones1. Objetivo: Describir un caso clinico de nesidioblastosis en una paciente en edad escolar, con historia de convulsiones tonicoclonicas desde 1 ano de edad, tratado con Oxcarbazepina. Presentando hipoglucemias sintomaticas desde 1 ano y medio, por lo que fue referida a la consulta de endocrinologia. Presentacion del caso clinico: Paciente femenina de 7 anos y 5 meses de edad cronologica, referida al departamento de endocrinologia con historia de enfermedad actual, caracterizada diaforesis y mareos; presenta movimientos tonico-clonicos generalizados, retroversion ocular con perdida del estado de conciencia (en 2 oportunidades), es trasladada a centro medico donde evidencian glucemia en 18-11-32-16 mg/dl respectivamente, colocan solucion dextrosa con mejoria momentanea. Permanece por 9 dias sin recuperacion completa y aparecen fiebre de 3 dias de evolucion; Es trasladada al Hospital Infantil Robert Reid Cabral (RRC), donde se estudia y se confirman las hipoglucemias, analiticas que revelan hormonas contrarreguladoras elevadas, niveles de insulina en 2,700 mui/ml. Se estabiliza con octreotide y se decide llevar a cirugia para pancreactectomia, realizandose laparotomia abierta. Biopsia trans-operatoria reporto: hiperplasia de las celulas de los islotes de Langerhans. Por lo que se extirpa un 95% de tejido pancreatico, presenta hiperglicemias y se inicia tratamiento con analogos de insulina de accion lenta (0.14 ud/kg/d), enzimas pancreaticas 10,000ud, 15 min previo a comidas y multivitaminicos. Al mes de la cirugia la paciente vuelve a presentar signos de hipoglicemias, se suspende la insulina y se ingresa, se verifican las hipoglicemias y se realiza una segunda intervencion quirurgica. Tambien se realiza exceresis de 5% de pancrea; segundada porcion del duodeno, con anastomosis terminal. Actualmente responde al tx con insulina analoga. Conclusion: La nesidioblastosis en una causa rara de hipoglucemia por hiperinsulinismo endogeno en el escolar, clinicamente es indistinguible del insulinoma; bioquimicamente es necesario documentar la hipoglucemia hiperinsulinemica durante el ayuno, el tratamiento de eleccion es la cirugia y seguimiento medico a los deficits secundarios a la misma. EnglishIntroduction: Necidioblastosis is defined as proliferation of pancreatic endocrine cells, which involves alterations in their distribution and differentiation. The number of the islets of Langerhans is lower than normal, with the endocrine cells distributed anarchically by the pancreatic parenchyma in the form of small nests or cords1. Objective: To describe a clinical case of nesidioblastosis in a patient of school age, with a history of tonic-clonic seizures from 1 year of age, treated with Oxcarbazepine. Presenting symptomatic hypoglycaemia from 1 year and a half, so it was referred to the endocrinology clinic. Presentation of the clinical case: Female patient of 7 years and 5 months of chronological age, referred to the department of endocrinology with a history of current illness, characterized by diaphoresis and dizziness; presents generalized tonic-clonic movements, ocular retroversion with loss of consciousness (on 2 occasions), is transferred to a medical center where they demonstrate glycemia at 18-11-32-16 mg / dl respectively, place dextrose solution with momentary improvement. It remains for 9 days without complete recovery and fever appears 3 days of evolution and is transferred to the Robert Reid Cabral Children's Hospital, where it is studied and confirmed hypoglycemia, laboratory tests that reveal high counter-regulating hormones, insulin levels in 2,700 mui / ml, stabilizes With octreotide and it is decided to carry out surgery for pancreactectomy, open laparotomy is performed. Trans-operative biopsy reported: hyperplasia of the islet cells of Langerhans. So 95% of pancreatic tissue is removed, presents hyperglycemia and treatment is started with slim-action insulin analogs (0.14 ud / kg / d) pancreatic enzymes 10,000d, 15 min prior to meals, multivitamin. One month after surgery, the patient presented signs of hypoglycemia again, insulin was discontinued and the patient was admitted, hypoglycemia was verified, and second surgical intervention was performed. An excess of 5% of the pancreas and 2nd portion of the duodenum was performed with an end-to-end anastomosis. Currently responding to tx with analogous insulin. Conclusion: Nesidioblastosis in a rare cause of hypoglycaemia due to endogenous hyperinsulinism in the school, clinically is indistinguishable from insulinoma; biochemically it is necessary to document hyperinsulinemic hypoglycaemia during fasting, the treatment of choice is surgery and medical treatment to the deficits 2nd to it.

Context: Insulin autoantibody syndrome (IAAS) is considered to be a rare cause of hyperinsulinaemic hypoglycaemia. Lack of familiarity with the varied clinical manifestations leads to underdiagnosis. Localization techniques aimed at insulin-secreting neoplasms and nesidioblastosis, which are expensive often are ordered when the correct diagnosis is not made. Aims: We describe the myriad of clinical manifestations associated with IAAS based on single centre experience. Settings and Design: Retrospective analysis of patients who got admitted with symptoms suggestive of hypoglycaemia and underwent mixed meal test and prolonged hypoglycaemic test from 2016 to 2019. Subjects and Methods: Retrospective data of 12 patients with IAAS who were diagnosed in the threeyear time period between 2016 and 2019 are included in this analysis. Clinical details, biochemical parameters and imaging modalities were analysed. Statistical Analysis: All analyses were performed with SPSS software (version 17). Results: Total of twelve patients 12 (5 male and 7 females) were identified as IAAS. Median age of presentation was 57 years. Median insulin levels and median C-peptide levels were 300 miu/ml and 18.5 ng/ml respectively. Only 3 (25%) patients had spontaneous resolution. Steroid induced remission occurred by 3 months in the remaining patients. Intermittent hyperglycaemia was seen in 9 (75%) patients. Implicatable drug use preceding the occurrence of the clinical symptoms was observed in five patients. Conclusion: IAAS is not uncommon in India. The diagnosis should be pursued in patients with hyperinsulinaemic hypoglycaemia especially when insulin levels are very high or when there is intermittent hyperglycaemia.

Receptors for the incretin glucagon-like peptide-1 (GLP-1R) have been found overexpressed in selected types of human tumors and may, therefore, play an increasingly important role in endocrine gastrointestinal tumor management. In particular, virtually all benign insulinomas express GLP-1R in high density. Targeting GLP-1R with indium-111, technetium-99m or gallium-68-labeled exendin-4 offers a new approach that permits the successful localization of small benign insulinomas. It is likely that this new non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. In contrast to benign insulinomas, malignant insulin-secreting neuroendocrine tumors express GLP-1R in only one-third of the cases, while they more often express the somatostatin subtype 2 receptors. Importantly, one of the two receptors appears to be always overexpressed. In special cases of endogenous hyperinsulinemic hypoglycemia (EHH), that is, in the context of MEN-1 or adult nesidioblastosis GLP-1R imaging is useful whereas in postprandial hypoglycemia in the context of bariatric surgery, GLP-1R imaging is probably not helpful. This review focuses on the potential use of GLP-1R imaging in the differential diagnosis of EHH.

Objective: Adult nesidioblastosis is characterized by endogenous hyperinsulinemia typically causing post-prandial hypoglycemia, and most commonly occurs post-Roux-en-Y gastric bypass. Methods: We report a unique case of nesidioblastosis occurring in a 67-year-old female. Results: A 5-year history of symptomatic hypoglycemia occurred in a patient with short bowel syndrome and type 2 diabetes mellitus (T2DM) managed previously with a glucagon-like peptide 1 (GLP-1) agonist, which achieved significant weight loss. Continuous glucose monitoring captured 42 hypoglycemia episodes in a 2-week period, and following an oral glucose tolerance test there was the suggestion of a hyperinsulinemia state. She was managed with an open distal pancreatectomy, and subsequently required medical therapy to maintain euglycemia. Conclusion: We present the first case of nesidioblastosis occurring in a patient with short bowel syndrome, pre-existing T2DM managed with a GLP-1 agonist which achieved significant weight loss, all of which we speculate could have predisposed to hypoglycemia and development of nesidioblastosis.

Key Clinical Message Despite growing evidence for GLP‐1R molecular‐based imaging, successful localization of insulinomas may require the use of multiple imaging modalities. Not all benign insulinomas express the GLP‐1R as expected. Our case demonstrates that there is a still an important role for traditional methods for the anatomical localization of an insulinoma.

“Nesidioblastosis”, later renamed as “persistent hyperinsulinemic hypoglycemia of infancy” presents as either focal or diffuse neo-differentiation of pancreatic Langerhans islet cells from the ductal epithelium. Differentiation of focal disease from diffuse involvement is crucial for optimal disease management. The current methods used to differentiate the two forms pre-operatively are invasive techniques. The definite role of imaging modalities to differentiate diffuse versus focal form has not yet been proven. Herein, we report a 15 day-old infant having diffuse nesidioblastosis, successfully demonstrated by Ga-68 DOTATATE positron emission tomography/computed tomography imaging that was histopathologically confirmed.Pankreasın Langerhans ada hücrelerinin duktus epitelinden yeniden farklılaşması olan “nesidioblastosis”, yeni adlandırılmasıyla “yenidoğanın inatçı hiperinsülinemik hipoglisemisi”, fokal ya da diffüz olarak iki şekilde görülebilir. Fokal formun diffüz olandan ayırt edilmesi hastalığın doğru yönetimi için son derece önemlidir. Bu iki formun cerrahi öncesi ayrımında kullanılan güncel metodlar invaziftir. Görüntülemenin diffüz formu fokal olandan ayırt etmedeki rolü tam olarak ortaya konamamıştır. Burada, Ga-68 DOTATATE pozitron emisyon tomografi/bilgisayarlı tomografi görüntüleme ile başarılı bir şekilde gösterilen ve histopatolojik olarak da doğrulanan diffüz nesidioblastosis hastası 15 günlük bir infant olgusunu sunduk.

We present a clinical case of rare and poorly diagnosable mediastinal teratoma containing elements of mature pancreas tissue, nesidioblastosis, and focal hyperplasia of neuroendocrine cells in a somatically healthy 25-year-old male. The main diagnostic difficulties are associated with the asymptomatic clinical course of mediastinal teratomas that are usually incidentally discovered during X-ray for other conditions. The pathology is characterized by pronounced morphological heterogeneity of the tumor; if the morphologist is not sufficiently qualified, this often results in a false-positive conclusion of neuroendocrine carcinoma, which, in turn, leads to an inadequate amount of treatment and a wrong prognosis in the patient. Therefore, for verification of the diagnosis, histological specimens should be examined by experts of institutions experienced in morphological differential diagnosis. In this case, an immunohistochemical study of the tumor for insulin, cytokeratins, and markers of neuroendocrine differentiation as well as measurement of the proliferation index Ki-67 in several areas are the key tests. This pathology is extremely rare, which leads to numerous misdiagnoses.

ObjectiveRoux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized and highly disabling complication of RYGB is postprandial hypoglycaemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like peptide-1 (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments are proposed, including dietary modification, GLP-1 antagonism, GLP-1 analogues and even surgical reversal, with none showing a more decided advantage over the others. A greater understanding of the pathophysiology of PPH could guide the development of new therapeutic strategies.MethodsWe studied a cohort of PPH patients at the Imperial Weight Center. We performed continuous glucose monitoring to characterize their altered glycaemic variability. We also performed a mixed meal test (MMT) and measured gut hormone concentrations.ResultsWe found increased glycaemic variability in our cohort of PPH patients, specifically a higher mean amplitude glucose excursion (MAGE) score of 4.9. We observed significantly greater and earlier increases in insulin, GLP-1 and glucagon in patients who had hypoglycaemia in response to an MMT (MMT Hypo) relative to those that did not (MMT Non-Hypo). No significant differences in oxyntomodulin, GIP or peptide YY secretion were seen between these two groups.ConclusionAn early peak in GLP-1 and glucagon may together trigger an exaggerated insulinotropic response to eating and consequent hypoglycaemia in patients with PPH.

Background. Insulinoma is the most common functional pancreatic neuroendocrine tumor originating from β-cells, with unregulated insulin production and rarely associated with MEN-I syndrome. Diagnosis and treatment of insulinoma are a challenge in the practice of endocrinologist. Aim. To determine on the basis of retrospective analysis the optimal approaches to the management of patients with organic hyperinsulinism. Material and methods. Medical records of 72 patients admitted with suspected organic hyperinsulinism had been screened and medical histories of patients with a confirmed diagnosis of organic hyperinsulinism were included into the analysis. Anamnesis, results of objective, laboratory and instrumental examinations, methods and results of the treatment were analyzed. Results. The diagnosis of insulinoma was confirmed in thirty two cases. Hypoglycemia was achieved within the first 48 hours after the start of the 72-hour fasting test in 100% of cases. Study results showed that in 50% of cases the size of the pancreatic neoplasm was more than 1.4 cm. Inverse correlation between tumor size and plasma glucose concentration at the time of hypoglycemia was found (r=–0.45; р=0.02). Surgical treatment was carried out in thirty out of 32 patients. Surgical enucleation of insulinoma was performed in 12 (40%) cases, distal pancreatectomy — in 18 (60%). Insulinoma was confirmed in 27 cases, while in three patients diagnosis of non-insulinoma pancreatogenous hypoglycemia («nesidioblastosis») was established according to histological findings. Positive clinical result was achieved after all surgeries. In postoperative period patients were discharged within 11—30 days. Patients without post-operative complications were discharged 13.0±1.4 days after surgery. Twelve (40%) patients developed post-operative complications. The duration of hospital stay in these cases was significantly longer 20.1±1.9 (р

Insulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal

Endogenous hyperinsulinism is an abnormal clinical condition that involves excessive insulin secretion, related in 55% of cases to insulinoma. Other causes are possible such as islet cell hyperplasia, nesidioblastosis or antibodies to insulin or to the insulin receptor. Differentiation between these diseases may be difficult despite the use of several morphological examinations. We report six patients operated on for endogenous hyperinsulinism from 1st January 2000 to 31st December 2015. Endogenous hyperinsulinism was caused by insulinoma in three cases, endocrine cells hyperplasia in two cases and no pathological lesions were found in the last case. All patients typically presented with adrenergic and neuroglycopenic symptoms with a low blood glucose level concomitant with high insulin and C-peptide levels. Computed tomography showed insulinoma in one case out of two. MRI was carried out four times and succeeded to locate the lesion in the two cases of insulinoma. Endoscopic ultrasound showed one insulinoma and provided false positive findings three times out of four. Intra operative ultrasound succeeded to localize the insulinoma in two cases but was false positive in two cases. Procedures were one duodenopancreatectomy, two left splenopancreatectomy and two enucleations. For the sixth case, no lesion was radiologically objectified. Hence, a left blind pancreatectomy was practised but the pathological examination showed normal pancreatic tissue. Our work showed that even if morphological examinations are suggestive of insulinoma, other causes of endogenous hyperinsulinism must be considered and therefore invasive explorations should be carried out.

Context. Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults. The diagnosis is further complicated in patients with kidney failure, since impaired renal function can cause hypoglycemia by itself and diagnostic criteria for this clinical scenario have not been developed yet. Case Description. We present the case report of a 36-year-old patient with end stage chronic kidney disease who presented to the emergency department because of hypoglycemia. However, the patient’s hypoglycemia did not respond well to medical treatment; the diagnosis of hyperinsulinemic hypoglycemia was made due to the presence of inappropriately high levels of insulin, proinsulin, and C-peptide during an episode of hypoglycemia. Imaging studies were performed without any conclusive findings; so selective intra-arterial pancreatic stimulation with hepatic venous sampling (SACTS) was done. Based on the results of this study the patient was referred for subtotal pancreatectomy. Classic criteria for the diagnosis of insulinoma with SACTS required a 2-fold increase in insulin levels but newer criteria suggest thresholds that are useful in the differential diagnosis of insulinoma and nesidioblastosis. In our patient, the former criteria were positive; however, the new criteria were not compatible with insulinoma but with nesidioblastosis, which was the final histopathological diagnosis. Conclusion. This seems to be the first case report of a patient with end stage chronic kidney disease and nesidioblastosis, as well as the first case of hyperinsulinemic hypoglycemia in the context of kidney failure diagnosed by SACTS. We consider this method to be very useful in patients with renal impairment because peripancreatic insulin levels do not depend on the renal function.

BACKGROUND Important causes of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adult patients are insulinoma and adult nesidioblastosis. Data on main symptoms in EHH are scarce and controversial. We analysed main symptoms of patients with EHH in the framework of two prospective studies investigating glucagon-like peptide-1 receptor imaging. METHODS Patients were referred from secondary European endocrine centres and endocrinologists. Inclusion criteria were biochemically proven EHH (glucose

UNLABELLED A previously healthy 18 year old female has repeated admissions over a six week period to the emergency department because of seizures. She has no previous history of epilepsy and denies any drug use. Imaging and electroencephalogram do not indicate epilepsy. Blood sugar levels are low on two occasions, 1.3 mmol / L and 1.7mmol / L (4.0 - 6.0 mmol / L). After further investigations the suspicion of an insulin-producing tumor arises. Extensive research and imaging is conducted to look for tumor growth without any findings. Subsequently she was sent abroad for further evaluation with a 11C-5HTP-PET scan, selective angiography with celiacography and an intra-arterial calcium stimulation test. She was diagnosed with nesidioblastosis. Here we will discuss the presentation and work-up of the medical case and review this rare causative disease. KEY WORDS repeated seizures, neuroglycopenic symptoms, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), endogenous hyperinsulinemic hypoglycemia, nesidioblastosis. Correspondence: Guðrun Mist Gunnarsdottir, gudrunmi@landspitali.is.

Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning and (111)indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results.

Background/purposeCongenital hyperinsulinism (CHI) is a rare condition causing severe hypoglycemia in neonates and infants due to dysregulation of insulin secretion. This study aimed to review 20 years' experience in the management of Taiwanese children with CHI.MethodsBetween 1990 and 2010, children diagnosed with CHI and followed up at the Pediatric Endocrine Clinic of the National Taiwan University Hospital were enrolled. Their medical records were thoroughly reviewed.ResultsIn total, 13 patients (8 boys and 5 girls) were enrolled, including six patients with onset of hypoglycemia within 1 month of age and seven patients at 4.0 ± 2.1 months of age. The birth weight standard deviation scores of these two age groups were 4.6 ± 1.8 and 1.4 ± 1.3 standard deviation score, respectively (p

Congenital hyperinsulinism (HI) is the most common cause of hypoglycemia in children. The risk of permanent brain injury in infants with HI continues to be as high as 25-50% due to delays in diagnosis and inadequate treatment. Congenital HI has been described since the birth of the JCEM under various terms, including "idiopathic hypoglycemia of infancy," "leucine-sensitive hypoglycemia," or "nesidioblastosis."In the past 20 years, it has become apparent that HI is caused by genetic defects in the pathways that regulate pancreatic β-cell insulin secretion.There are now 11 genes associated with monogenic forms of HI (ABCC8, KCNJ11, GLUD1, GCK, HADH1, UCP2, MCT1, HNF4A, HNF1A, HK1, PGM1), as well as several syndromic genetic forms of HI (eg, Beckwith-Wiedemann, Kabuki, and Turner syndromes). HI is also the cause of hypoglycemia in transitional neonatal hypoglycemia and in persistent hypoglycemia in various groups of high-risk neonates (such as birth asphyxia, small for gestational age birthweight, infant of diabetic mother). Management of HI is one of the most difficult problems faced by pediatric endocrinologists and frequently requires difficult choices, such as near-total pancreatectomy and/or highly intensive care with continuous tube feedings. For 50 years, diazoxide, a KATP channel agonist, has been the primary drug for infants with HI; however, it is ineffective in most cases with mutations of ABCC8 or KCNJ11, which constitute the majority of infants with monogenic HI.Genetic mutation testing has become standard of care for infants with HI and has proven to be useful not only in projecting prognosis and family counseling, but also in diagnosing infants with surgically curable focal HI lesions. (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET scans have been found to be highly accurate for localizing such focal lesions preoperatively. New drugs under investigation provide hope for improving the outcomes of children with HI.

To explore the role of 68Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia. We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases. Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up. This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.

Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) due to the changes in gut hormonal milieu. Physicians should be aware of this complication to ensure timely and effective treatment of post-RYGB patients, who present to them with hypoglycemic symptoms. Possible causes of hypoglycemia in these patients include late dumping syndrome, nesidioblastosis and rarely insulinoma. Systematic evaluation including history, biochemical analysis, and diagnostic testing might help in distinguishing among these diagnoses. Continuous glucose monitoring is also a valuable tool, revealing the episodes in the natural environment and can also be used to monitor treatment success. Treatment should begin with strict low carbohydrate diet, followed by medication therapy. Therapy with diazoxide, acarbose, calcium channel blockers and octreotide have been proven to be beneficial, but the response apparently is highly variable. When other treatment options fail, surgical options can be considered.