Nesidioblastosis and Subsequent Diabetes Mellitus in a Dog with Hyperinsulinemic Hypoglycemia Treated with Partial Pancreatectomy.

A 6.5 yr old castrated male mixed-breed dog was presented for clinical signs associated with hypoglycemia. Hyperinsulinemic hypoglycemia was diagnosed as the cause of the persistent hypoglycemia. No obvious pancreatic mass was seen on abdominal computed tomography and exploratory laparotomy. A partial pancreatectomy was performed with the suspicion of an insulinoma-causing hyperinsulinemic hypoglycemia. Nesidioblastosis was diagnosed based clinical, biochemical, and histopathologic findings. There was beta cell hyperplasia and no evidence of neoplasia. The dog was euglycemic postoperatively after a partial pancreatectomy. Long-term follow-up after 2 yr revealed that the dog was diagnosed with diabetes mellitus.

Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens.

BACKGROUND: Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. METHODS: We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. RESULTS: There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. CONCLUSIONS: Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in ß-cells," has potential diagnostic value.

Hyperinsulinemic hypoglycemia in adults. Nesidioblastosis case report and review of the literature.

Hypoglycemia due to endogenous hyperinsulinism usually occurs in 2 pathological situations: the most frequent is insulinoma and, secondly, nesidioblastosis or also known as non-insulinoma pancreatic hypoglycemic syndrome. Nesidioblastosis is a rare cause of hyperinsulinic hypoglycemia in adults. We present the clinical case of an adult patient with recurrent hypoglycemia secondary to nesidioblastosis.

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.

Nesidioblastosis and Insulinoma: A Rare Coexistence and a Therapeutic Challenge.

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 ß-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.

Concurrent Adult-Onset Diffuse ß-Cell Nesidioblastosis and Pancreatic Neuroendocrine Tumor: A Case Report and Review of the Literature.

Nesidioblastosis is an uncommon cause of organic persistent hyperinsulinemic hypoglycemia in adults. We report a case of adult-onset diffuse ß-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 ß-cell hyperplasia and nuclear pleomorphism consistent with ß-cell nesidioblastosis. The patient's blood glucose levels normalized after completion pancreatectomy. While ß-cell nesidioblastosis and insulinomas can coexist in the same patient, pathologists should be aware of ß-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.

A Case Report of Insulinoma Relapse on Background Nesidioblastosis: A Rare Cause of Adult Hypoglycemia.

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.

Resolution of hyperinsulinemic hypoglycemia following partial pancreatectomy in a dog with nesidioblastosis.

CASE DESCRIPTION A 6-year-old castrated male Australian Shepherd was evaluated because of a recent onset of persistent hypoglycemia. CLINICAL FINDINGS Physical examination results were generally unremarkable. No abnormalities were detected on thoracic radiographs, and abdominal ultrasonography revealed no obvious pancreatic lesion. Hematologic analysis revealed hypoglycemia with a high serum insulin-to-glucose concentration ratio. TREATMENT AND OUTCOME Insulinoma was suspected; medical treatment with prednisone was initiated, and exploratory laparotomy was performed. No pancreatic lesions or masses were observed. Partial left pancreatectomy and hepatic and local lymph node biopsies were performed. Histologic examination revealed islet cell hypertrophy and hyperplasia, with no evidence of neoplasia. Results of a PCR assay of the pancreatic tissue for Bartonella infection were negative. Clinical, biochemical, and histopathologic findings were compatible with nesidioblastosis. The clinical signs, including hypoglycemia, resolved after surgery. On follow-up examination 8 months later, the dog was apparently healthy and results of a CBC and serum biochemical analysis, including blood glucose concentration, were within respective reference ranges. CLINICAL RELEVANCE To our knowledge, this is the first report of nesidioblastosis in a dog for which clinical signs and clinicopathologic abnormalities resolved after partial pancreatectomy. Although extremely rare, nesidioblastosis should be considered a differential diagnosis in dogs with signs suggestive of insulinoma.

Unsuccessful Desensitization in a Child with Hypersensitivity to Diazoxide.

No Abstract.

The diagnosis and management of congenital and adult-onset hyperinsulinism (nesidioblastosis) - literature review.

Congenital and adult-onset hyperinsulinism (CHI) must be taken under consideration in the differential diagnosis of hypoglycaemia symptoms with endogenous hyperinsulinism, especially in cases in which there was failure to find an insulinoma. Histological examination is necessary for a definitive diagnosis. CHI is a disorder with three histopathological variants: focal CHI, diffuse CHI, and atypical CHI. These variants are clinically indistinguishable. According to published statistics, 0.5 to 5% of nesidioblastosis cases occur in adults. Clinical manifestation ranges from mildly symptomatic up to life-threatening hypoglycaemia. Early diagnosis and treatment are important in young and very young patients because early treatment accounts for favourable mental outcomes.

Masa pancreática: una presentación inhabitual de nesidioblastosis en el adulto / Pancreatic mass: an unusual presentation of nesidioblastosis in adults

A 41-year-old woman, multiparous of 4, with personal or familiar history of diabetes, with a history of Nissen fundoplication due to pathological gastro-oesophageal reflux, is refer to an endocrinologjst during her post-operatiye follow up, 4 months after her surgery for a 14 kg weight loss in 10 months and symtomatic hypoglycemia to repetition. A positive prolonged fasting test for hypoglycemia was performed. In addition, abdominal computed axial tomography was performed, which resulted normal and endosonography, showing a lesion on the head of the pancreas. Octreoscan positive for pancreatic head focal lesion with positive somatostatin receptors compatible with insulinoma. Whipple surgery was performed where surgeon palpated pancreatic tumor, biopsy showed tissue compatible with diffuse nesidioblastosis. In the postoperative period, the patient decreased frequency and intensity of hypoglycemic episodes compared to their previous stage. Control prolonged fasting test and Octreoscan were within normal ranges. However, 4 months after surgery, the patient presented hypoglycemia of lower intensity and frequency than before surgery. Currently he remains in control with nutritionist and endocrinologist, mainly adjusting diet and with good control glycemias.

Anaesthetic Management Of Nesidioblastosis In Two Infants.

Nesidioblastosis is the most common cause of non-transient, recurrent and persistent hypoglycaemia in neonates and infants. It is a disorder of diffuse proliferation of beta cells of the pancreas leading to hyperinsulinemia and hypoglycaemia. The main aim is to prevent the severe episodes of hypoglycaemia which can cause damage to the brain and/or mental retardation. In this case report we present two cases of nesidioblastosis and their perioperative anaesthetic course for near-total pancreatectomy. First case was a 7 months old female who had repeated episodes of convulsions since birth. Second case was a 4-month-old female child who again presented with seizures. The challenges faced in the perioperative period were the management of perioperative blood glucose levels and haemodynamic stability.

Robotic Near-Total Pancreatectomy for Nesidioblastosis after Bariatric Surgery.

Postprandial symptoms of neuroglycopenia after bariatric surgery may result as a consequence of endogenous hyperinsulinemic hypoglycemia (nesidioblastosis) not dumping syndrome. Pancreatectomy is an acceptable treatment for this condition. We present the video of a case of near-total distal robotic pancreactectomy for the treatment of nesidioblastosis after Roux-en-Y gastric bypass. Robotic pancreatectomy is an alternative to the treatment of nesidioblastosis after Roux-en-Y gastric bypass.

Recidiva de fibroadenoma juvenil en paciente afecta de síndrome de Beckwith-Wiedemann / Recurrence of juvenile fibroadenoma in a patient with Beckwith-Wiedemann syndrome

No disponible

[Repeated non-epileptic seizures in a previously healthy young woman - a case report].

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 1.7mmól / 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.

Intraoperative portal vein insulin assay combined with occlusion of the pancreas for complex pancreatogenous hypoglycemia: Two cases report.

Intraoperative localization and confirmation of complete resection of the hypersecreting tissue are the 2 main challenges in the management of pancreatogenous hypoglycemia. Here, we report our experience with intraoperative portal vein insulin assay combined with occlusion of the pancreas in the management of pancreatogenous hypoglycemia. Clinical courses of 2 patients with biochemical evidence of a pancreatogenous hypoglycemia were studied. The preoperative diagnosis was multiple endocrine neoplasia 1 (MEN-1) and nesidioblastosis, respectively. Rapid intraoperative portal vein insulin assay combined with occlusion of the pancreas was used to localize and confirm complete excision of the hypersecreting tissue. Hypoglycemia was successfully treated in both the patients. In the MEN-1 patient, 2 small tumors in the head of pancreas were not resected, as they were deemed noninsulin secreting by intraoperative portal vein insulin assay, thus avoiding a total pancreatectomy. In the patient with nesidioblastosis, using intraoperative portal vein insulin assay combined with occlusion of the pancreas, an appropriate amount of pancreatic tissue was resected thereby avoiding recurrence and diabetes. This technique may be of particular value in patients with complex conditions such as MEN-1 and nesidioblastosis, to localize and achieve complete resection of hypersecreting pancreatic tissue.

Hyperinsulinemic Hypoglycemia after Bariatric Surgery: Diagnosis and Management Experience from a Spanish Multicenter Registry.

BACKGROUND: Severe postprandial hypoglycemia after bariatric surgery is a rare but invalidating complication. Our aim was to describe the different tests performed for its diagnosis and their outcomes as well as the response to the prescribed pharmacological and surgical treatments. METHODS: Multicenter, retrospective systematic review of cases with recurrent severe postprandial hypoglycemia. RESULTS: Over 11 years of follow-up, 22 patients were identified. The test most used to provoke hypoglycemia was the oral glucose load test followed by the mixed meal test which was the least standardized test. With pharmacological treatment, 3 patients were symptom-free (with octreotide) and in 12 patients hypoglycemic episodes were attenuated. Seven patients had persistent hypoglycemic episodes and underwent surgery. Partial pancreatectomy was performed in 3 patients who had positive selective arterial calcium stimulation, and nesidioblastosis was confirmed in 2 patients. Reconversion to normal anatomy was performed in 3 patients, and 1 patient underwent a resection of the 'candy cane' roux limb, with resolution of hypoglycemia in all cases. CONCLUSIONS: There is high heterogeneity in the evaluation and treatment options for postoperative hypoglycemia. In patients that do not respond to pharmacological treatment, reconstruction of gastrojejunal continuity may be the safest and most successful procedure.

Synchronous Nesidioblastosis, Endocrine Microadenoma, and Intraductal Papillary Mucinous Neoplasia in a Man Presenting With Hyperinsulinemic Hypoglycemia.

Herein, we report the first case of concomitant nesidioblastosis, pancreatic neuroendocrine tumor, and intraductal papillary mucinous neoplasia. The combination is significant as each of these pathological entities is independently very rare. The patient was a 33-year-old man who presented with symptomatic hyperinsulinemic hypoglycemia and no risk factors for pancreatic disease. Abdominal imaging showed an isolated 12 mm pancreatic lesion, whilst selective arterial calcium stimulation testing demonstrated multiple territories of insulin excess. He proceeded to subtotal pancreatectomy. Histopathology revealed an endocrine microadenoma, α and ß cell nesidioblastosis, and multifocal intraductal papillary mucinous neoplasia. The endocrine microadenoma and nesidioblastosis stained for insulin, suggesting both likely contributed to hypoglycemia. Glucagon immunohistochemistry was also positive, though there were no clinical features of glucagon excess. Hypoglycemia resolved postoperatively. This case and other evidence from the literature suggest that hyperplasia and neoplasia may occur sequentially in the pancreas, and that endocrine and exocrine tumorigenesis may be linked in some individuals. Further study is required to identify a unifying mechanism, and to elucidate potential ramifications in the management of patients with pancreatic neoplasms.

Nesidioblastosis coexisting with non-functioning islet cell tumour in an adult.

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognized disorder of persistent hypoglycaemia in infants, it is extremely rare in adults.We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis.

Refractory hypoglycaemia in patient with gastric outlet obstruction.

A 68-year-old male with a longstanding history of severe gastric outlet obstruction secondary to peptic stricture was found unconscious at home with profound hypoglycaemia. He denied history of fasting, diabetes mellitus or use of hypoglycaemic agents. Systemic examination and metabolic profile were unremarkable. Hypoglycaemic episodes persisted during hospitalisation, requiring continuous intravenous dextrose and eventually diazoxide. Further investigative work up, including 72 h fasting study, revealed a hyperinsulinemic state. MRI and endoscopic ultrasound were unremarkable but mesenteric angiography with hepatic venous sampling revealed a subtle area of hypervascularity in the head of pancreas. An exploratory laparotomy was then performed and resulted in resection of a nodular lesion in the head of pancreas with retrocolic gastrojejunostomy for repair of pyloric stenosis. Histopathology of pancreatic nodule confirmed nesidioblastosis. Postoperatively the patient was weaned of parenteral dextrose and did not have any further episodes of hypoglycaemia.