Noninsulinoma Pancreatogenous Hypoglycemia Syndrome Research Articles

Histopathological features of non-insulinoma pancreatogenous hypoglycemia syndrome: A rare cause of hypoglycemia in non-diabetic adults

Histopathological features of non-insulinoma pancreatogenous hypoglycemia syndrome: A rare cause of hypoglycemia in non-diabetic adults

SAT139 Non-insulinoma Pancreatogenous Hypoglycemia Syndrome In A Patient With 1p36 Deletion Syndrome

Abstract Disclosure: E.D. Auckley: None. M.A. Arosemena: None. L. Philipson: None. Background: 1p36 deletion syndrome comprises a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. There has been no report of associated hypoglycemia with this syndrome. Nesidioblastosis, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), is understood as a rare condition defined by diffuse pancreatic hypertrophy with subsequent hyperinsulinemic hypoglycemia. Diagnosis requires serologic workup consistent with endogenous hyperinsulinemic hypoglycemia, intraarterial calcium stimulation positive for inappropriately elevated insulin secretion, and imaging studies without identified masses. Clinical Case: A 21-year-old female with 1p36 deletion syndrome (seizure disorder, cerebral palsy, vision loss and heart failure) was admitted to the hospital due to persistent falls. On admission vital signs were within normal limits, and physical exam revealed a thin non-verbal patient without significant other findings. During hospitalization and prolonged fasting periods of approximately 14-18 hours related to poor appetite she developed several episodes of hypoglycemia with serum glucose as low as 57 mg/dl. As patient was non-verbal at baseline, symptoms of hypoglycemia such as sweating, lightheadedness or shakiness were not confirmed. Even when she started to eat, hypoglycemic events continued to occur. Dextrose containing fluids (Dextrose 5% and later 10%) were added to try to maintain blood sugars within the normal range. Nevertheless, she continued to develop hypoglycemia. Endocrinology service was consulted and recommended to obtain a critical sample. A critical sample revealed serum glucose of 59 mg/dl, insulin level of 20.6 mcU/mL, proinsulin of 33 pmol/L, and beta-hydroxybutyrate of <0.10 mmol/L. Insulin antibodies was negative. Adrenal insufficiency was unlikely due to a normal 9 am cortisol level of 13.7 ug/dl. Due to the presence of hyperinsulinemic hypoglycemia further workup was conducted. A CT of the abdomen with a pancreatic protocol and 68Ga-DOTATATE PET/CT scan was negative for a pancreatic mass. Endoscopic ultrasound did not reveal a clear pancreatic mass either. This was followed by a calcium stimulation test which showed a two-fold increase in insulin levels in all 3 catheterized pancreatic territories. In the absence of a discrete mass, non-surgical management was recommended. For hypoglycemia management patient was started on octreotide injections with resolution of hypoglycemia. Prior to discharge she was switched to lanreotide and was discharged to continue monthly lanreotide injections. Conclusion: To our knowledge, this is the first case reported of NIPHS in a patient with a mutation in 1p36 deletion. Hyperinsulinism in the setting of diabetes has been reported in this syndrome1 but to our knowledge no cases of hypoglycemia with NIPHS have been reported. Presentation: Saturday, June 17, 2023

Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia.

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.

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

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

S1881 A Case of Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome in a Cerebral Palsy Patient Where Diagnosis and Treatment Was Delayed Due to Continuous PEG-Tube Feeding

Introduction: Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), a rare cause of post-prandial hypoglycemia, presents with neuroglycopenia and negative localization studies for insulinoma. We present a case of NIPHS in a female whose cerebral palsy and continuous tube feeds created difficulty in establishing her diagnosis. Case Description/Methods: A 22-year-old female with cerebral palsy (baseline nonverbal status and quadriplegia) presented to the hospital with 5 days of lethargy. She had no fevers or seizures at home and had been on continuous enteral nutrition via PEG tube for two years. Vitals were normal. Physical exam showed decreased responsiveness and absent spontaneous eye opening on top of baseline posturing and muscle spasticity. Infectious workup was negative. Labs found a decreased blood glucose of 72mg/dl. As patient’s mentation improved overnight, hospital tube feeds were restarted at a reduced rate. Patient’s morning blood glucose was 66mg/dl so tube feeding rate was increased. Blood glucose further declined to 42mg/dl a few hours later. Continuous dextrose infusions, high carbohydrate tube feeds, and continuous glucagon drip were administered with minimal benefit. Insulin, proinsulin, and c-peptide were found to be within normal range. Insulin antibody test was also negative. Abdominal ultrasound and CT found no lesions in the pancreas or other acute pathology. Patient was deemed to have NIPHS. Acarbose was initiated with resolution of hypoglycemia and improvement in mentation and patient was discharged home with no further complications. Discussion: The postprandial hypoglycemia differential in non-nondiabetic patients includes insulinoma, post bariatric surgery hypoglycemia, dumping syndrome, insulin autoimmunity, postprandial syndrome, and NIPHS. Our patient’s cerebral palsy and nonverbal status masked the neuroglycopenic symptoms typical in NIPHS. Continuous home tube feeds via PEG initially prevented us from determining the postprandial timing of her lethargy. These clues could have pointed us in the direction of NIPHS sooner which would have allowed for more prompt utilization of acarbose, earlier discharge and avoidance of the use of dextrose infusions, glucagon, and high carbohydrate tube feeds. The high carbohydrate diet likely worsened our patient’s condition as reports indicate free carbohydrate reduction improves the clinical status of NIPHS patients. Fortunately, we were able to administer acarbose to resolve our patient’s condition without incident.

Combined laparoscopic Roux-en-Y gastric bypass reversal and gastric banding to treat severe hyperinsulinemic hypoglycemia: A case report and surgical video.

Non insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a recently described complication of Roux-en-Y gastric bypass (RYGB) characterised by pathologic features of nesidioblastosis and hyperinsulinemic hypoglycemias that can occur months to years after surgery. Increased incretin production appears to be one of the involved mechanisms. Currently, there is no Gold Standard treatment. We present the case of a 57-year-old woman with a history of silastic ring vertical gastroplasty (SRVG) converted into RYGB who suffered from severe daily episodes of neuroglycopenia due to NIPHS, with poor response to conservative and medical treatments. At first, as it is suggested in recent literature, we decided to evaluate whether reversal would efficiently reduce episodes of hypoglycemia by attempting gastrostomy tubing of the remaining stomach. Since gastrostomy proved to be efficient, we reversed the RYGB laparoscopically and added a gastric banding to keep control over the patient's weight. After an asymptomatic period of two months, mild hypoglycemias recurred, on average once every three weeks, easily managed by sugar ingestion. A preexisting gastroparesis was worsened by the intervention, possibly caused by vagus nerve injury secondary to the multiple gastric procedures. A year later, the patient returned to a regular lifestyle. Her weight gain was limited to 8 kg thanks to appropriate adjustments of the gastric band. Treatment of NIPHS includes appropriate diet, pharmacotherapy and surgical procedures; partial or total pancreatectomy, laparoscopic reversal of RYGB (with or without sleeve gastrectomy) and gastric banding have been proposed. This is the first described case of severe NIPHS after RYGB successfully treated with combined laparoscopic reversal of gastric bypass and gastric banding to avoid weight regain. We expect this novel approach will help to overcome hypoglycemic episodes from NIPHS, while maintaining weight control and preventing the resurgence of obesity-related comorbidities. Further studies with long term follow-up are necessary. • Non insulinoma pancreatogenous hypoglycemia syndrome is a recently described complication of Roux-en-Y gastric bypass • Currently, there is no Gold Standard treatment. • In this case, we successfully performed a combined laparoscopic reversal of gastric bypass and gastric banding

S2754 Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) and Severe Portein-Calorie Malnutrition; Unexpected Outcomes After Gastric Bypass Surgery

INTRODUCTION: Bariatric surgery is the most effective way to achieve a clinically significant weight loss in severely obese patients but rarely it can cause Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) and severe protein-calorie malnutrition which happened in our case. CASE DESCRIPTION/METHODS: 49 years old female with a history of Roux-en-Y gastric bypass (2005) admitted for altered mental status secondary to hypoglycemia ( FS 25) and multiple electrolyte abnormalities ( Na 158, K 2.5, BUN 50, Cr 2.5). She was acutely managed resulting in improvement in mental status. She endorsed continued weight loss for the last 6 months along with anorexia. Upper endoscopy and Colonoscopy did not reveal any cause. Her hospital course was complicated by recurrent episodes of hypoglycemia. Further workup raised the possibility of Noninsulinoma pancreatogenous hypoglycemia syndrome(NIPHS) for which diazoxide was started. A feeding tube was placed in the remnant stomach because of continued weight loss. The patient was followed after 2 months by the bariatric surgery team and underwent reversal of RYGB with uneventful post-op recovery. DISCUSSION: Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) and severe protein-calorie malnutrition are extremely rare complications after bariatric surgery. NIPHS is characterized by endogenous hyperinsulinemic hypoglycemia that is not caused by an insulinoma. Histopathology specimens have revealed islet cell hypertrophy and sometimes islet cell hyperplasia. The predominant clinical feature is postprandial hypoglycemia. Biochemical findings are similar to insulinoma which include elevated plasma insulin, C-peptide, and proinsulin concentrations. Definitive diagnosis is made by EUS guided pancreatic biopsy which might be difficult to do in RYGB patients. In case reports, octreotide, verapamil, diazoxide, and acarbose have reportedly improved hypoglycemic symptoms. In severe cases, partial or subtotal pancreatectomy is performed. Severe protein-calorie malnutrition can cause continued weight loss years after bariatric surgery. It can be managed successfully with nutritional support in most of the cases. Patients may also require a psychological evaluation and/or counseling to determine the degree to which a psychosocial etiology is involved. It is important to rule out and treat all possible underlying mechanical and behavioral causes before considering a surgical revision such as the lengthening of the common channel or surgical reversal.

Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017-2018): Congenital hyperinsulinism, insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata's disease).

Aims/IntroductionWe 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 MethodsA 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.ResultsA 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.ConclusionsThe 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.

SUN-317 Reactive Hypoglycemia in a Post-Partum Patient: A Diagnostic Conundrum

Background: Both insulinoma and non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) are known causes of insulin overproduction. The common presentation of insulinoma is symptomatic fasting hypoglycemia. The stereotyped presentation of NIPHS is reactive hypoglycemia. This is a case report of a patient with reactive hypoglycemia more typical of NIPHS who was later diagnosed with insulinoma by endoscopy. Clinical Case: A 34-year-old previously healthy female four weeks status post uncomplicated vaginal delivery presented with multiple episodes of hypoglycemia with blood glucose <60 mg/dL; reactive hypoglycemia was more frequent. CT scan showed no pancreatic masses, and lab work drawn during a period of fasting hypoglycemia demonstrated c-peptide level of 2.8 ng/ml and an insulin level of 4 uIU/ml. The working diagnosis was NIPHS; she was managed initially with acarbose 25mg every 8 hours and diet with goal 15-30g of net carbohydrates per day. She initially experienced reduced episodes of hypoglycemia with acarbose with blood glucose in the 70-90 mg/dL range but was unable to sustain glucose levels above 100 mg/dL. After four days on acarbose the patient was switched to diazoxide 1mg/kg every 8 hours, which resulted in frequent sugars in the 60-70 mg/dL range, so acarbose was resumed. Subsequent endoscopic ultrasound demonstrated insulinoma. Clinical Lessons: One would expect that acarbose and low carbohydrate diet would be ineffective in a patient with an insulinoma; however, this patient experienced reduction of hypoglycemic episodes with these therapies. Given her improved blood sugars on acarbose, we postulate that she had both an insulinoma and some degree of beta cell hyperplasia, possibly related to her recent pregnancy. This case demonstrates a challenging diagnostic dilemma and reveals subtle nuances in the workup and management of a post-partum patient with hypoglycemia. It also raises interesting questions regarding the effects of pregnancy hormones on the growth and presentation of insulinomas. Estrogen has been shown to inhibit rat insulinoma cell mitophagy in vitro.1 It is possible our patient experienced increased growth of the insulinoma during pregnancy due to a similar estrogen mediated mechanism but was simultaneously protected from severe hypoglycemia due to insulin resistance of pregnancy. In the less insulin resistant post-partum state, hypoglycemia ensued. Further investigation should be done to evaluate why some insulinomas present with post-prandial hypoglycemia, to determine an effective medical therapy for NIPHS and insulinoma prior to surgical intervention, and to fully elucidate effects of pregnancy on the presentation of insulinoma. 1. Zhang L., Zhao Y., Guo L. 17beta-estradiol protects INS-1 insulinoma cells from mitophagy via G protein-coupled estrogen receptors and the PI3K/Akt signaling pathway. Int J Mol Med. 2018;41:2839–2846.

Persistent hypoglycemia in a nondiabetic patient after Roux-en-Y gastric bypass: a case of noninsulinoma pancreatogenous hypoglycemia syndrome

Persistent hypoglycemia in a nondiabetic patient after Roux-en-Y gastric bypass: a case of noninsulinoma pancreatogenous hypoglycemia syndrome

A case of multiple endocrine neoplasia type 1 (MEN1) with non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) responding to medical treatment with diazoxide

A case of multiple endocrine neoplasia type 1 (MEN1) with non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) responding to medical treatment with diazoxide

MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia.

Glucose is the main substrate utilized by the brain and as such multiple regulatory mechanisms exist to maintain glucose concentrations. When these mechanisms fail or are defective, hypoglycemia ensues. Due to these robust mechanisms, hypoglycemia is uncommon and usually occurs in the setting of the treatment of diabetes using glucose-lowering agents such as sulfonylureas or insulin. The symptoms of hypoglycemia are non-specific and as such it is important to confirm hypoglycemia by establishing the presence of Whipple's triad before embarking on an evaluation for hypoglycemia. When possible, evaluation of hypoglycemia should be carried out at the time of spontaneous occurrence of symptoms. If this is not possible then one would want to create the circumstances under which symptoms occur. In cases where symptoms occur in the post absorptive state, a 72-h fast should be performed. Likewise, if symptoms occur after a meal then a mixed meal study may be the test of choice. The causes of endogenous hyperinsulinemic hypoglycemia include insulinoma, post-bariatric hypoglycemia and noninsulinoma pancreatogenous hypoglycemia syndrome. Autoimmune hypoglycemia syndrome is clinically and biochemically similar to insulinoma but associated with high levels of insulin antibodies and plasma insulin. Other important causes of hypoglycemia include medications, non-islet cell tumors, hormonal deficiencies, critical illness and factitious hypoglycemia. We provide an overview of the pathogenesis and management of hypoglycemia in these situations.

Post–Gastric Bypass Hypoglycemia in a Patient with End-Stage Renal Disease

ABSTRACT Objective: To highlight an atypical presentation of post–gastric bypass hypoglycemia complicated by end-stage renal disease (ESRD). Methods: A case report of relevant medical history, in addition to diagnostic and treatment challenges are presented. Results: We describe a 42-year-old female who presented for syncope due to hypoglycemia. She had a history of ESRD on dialysis as well as Roux-en-Y gastric bypass (RYGB) 10 years prior to admission. Diagnostic evaluation, although confounded by renal failure, favored insulin-mediated hypoglycemia and selective arterial calcium stimulation testing suggested noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Failure of multiple medical therapies ultimately led to partial pancreatic resection, with pathology confirming the diagnosis, and clinical improvement. Conclusion: Although hypoglycemia after gastric bypass is a well-recognized disorder, the pathophysiology and best treatment plan is still under investigation. Our case report of surgical ...

Spontaneous hypoglycemia: diagnostic evaluation and management

Spontaneous hypoglycemia is a puzzling clinical problem and an important reason for referral to endocrinologists. Several clinical conditions such as insulinomas, non-insulinoma pancreatogenous hypoglycemia syndrome, insulin autoimmune syndrome, postprandial hypoglycemia (reactive hypoglycemia), non-islet cell tumor hypoglycemia, primary adrenal insufficiency, hypopituitarism, and critical illness can be associated with spontaneous hypoglycemia. Rarely, in patients with mental health issues, factious hypoglycemia from extrinsic insulin use or ingestion of oral hypoglycemic agents can obfuscate the clinical picture for clinicians trying to identify an organic cause. In those presenting with Whipple's triad (symptoms±signs of hypoglycemia, low plasma glucose, and resolution symptoms±signs after hypoglycemia correction), a 72-h supervised fast test with measurement of plasma insulin, c-peptide, pro-insulin, and beta-hydroxybutyrate levels, coupled with plasma/urine sulphonylurea screen, forms the first step in diagnostic evaluation. A mixed meal test is preferable for those with predominantly postprandial symptoms. Additional non-invasive and/or invasive diagnostic evaluation is necessary if an organic hypoglycemic disorder is suspected. With the aid of a few brief clinical case scenarios, we discuss the diagnostic evaluation and management of spontaneous hypoglycemia through this comprehensive article.

Management of Refractory Noninsulinoma Pancreatogenous Hypoglycemia Syndrome with Gastric Bypass Reversal: A Case Report and Review of the Literature.

Background. Roux-en-Y gastric bypass (RYGB) is a commonly performed, effective bariatric procedure; however, rarely, complications such as postprandial hypoglycemia due to noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) may ensue. Management of refractory NIPHS is challenging. We report a case that was successfully treated with RYGB reversal. Case Report. A 58-year-old male with history of RYGB nine months earlier for morbid obesity presented for evaluation of postprandial, hypoglycemic seizures. Testing for insulin level, insulin antibodies, oral hypoglycemic agents, pituitary axis hormone levels, and cortisol stimulation was unrevealing. Computed tomography (CT) scan of the abdomen was unremarkable. A 72-hour fast was completed without hypoglycemia. Mixed meal testing demonstrated endogenous hyperinsulinemic hypoglycemia (EHH) and selective arterial calcium stimulation testing (SACST) was positive. Strict dietary modifications, maximal medical therapy, gastrostomy tube feeding, and stomal reduction failed to alleviate symptoms. Ultimately, he underwent laparoscopic reversal of RYGB. Now, 9 months after reversal, he has markedly reduced hypoglycemia burden. Discussion. Hyperfunctioning islets secondary to exaggerated incretin response and altered intestinal nutrient delivery are hypothesized to be causative in NIPHS. For refractory cases, there is increasing skepticism about the safety and efficacy of pancreatic resection. RYGB reversal may be successful.

Reversible Adrenal Insufficiency in Three Patients With Post-Roux-en-Y Gastric Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome.

Objective. Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a disorder of endogenous hyperinsulinemia that is clinically distinguishable from insulinoma, with a greater preponderance after Roux-en-Y gastric bypass (RYBG). Hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory hormone responses to hypoglycemia, and consequent suppression of the hypothalamic–pituitary–adrenal (HPA) axis. This case series describes 3 individuals who were diagnosed with adrenal insufficiency (AI) after undergoing RYGB, complicated by NIPHS. Methods. A retrospective chart review was performed for each individual. Chart review applied particular attention to the onset of hyperinsulinemic hypoglycemia following bariatric surgery and the dynamic testing leading to the diagnoses of NIPHS and AI. Results. In each case, reactive hypoglycemia ensued within months to years after RYGB. Cosyntropin stimulation testing confirmed the diagnosis of AI. Hydrocortisone therapy reduced the frequency and severity of hypoglycemia and was continued until successful medical and/or surgical management of hyperinsulinism occurred. Follow-up testing of the HPA axis demonstrated resolution of AI. In all cases, hydrocortisone therapy was finally discontinued without incident. Conclusion. We speculate that transient AI is a potential complication in patients who experience recurrent hyperinsulinemic hypoglycemia after RYGB. The putative mechanism for this observation may be attenuation of the HPA axis after prolonged exposure to severe, recurrent hypoglycemia. We conclude that biochemical screening for AI should be considered in individuals who develop post-RYGB hyperinsulinemic hypoglycemia. If AI is diagnosed, supportive treatment should be maintained until hyperinsulinemic hypoglycemia has been managed effectively.

Incomplete Picture

A review article can be expected to provide a critical appraisal of published scientific evidence, especially if the bibliography is updated to include 2011. This was not done to a sufficient degree in all subchapters on the diagnostic evaluation and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NET) (1). The enormous importance of surgical resection undertaken with a curative intent, including surgery to lymph nodes and hepatic metastases in combination with microparticle liver embolization (transcatheter arterial embolization, TAE) and/or radiopeptide therapy in mostly metastasized NET was dealt with to an unsatisfactory extent. Such complex planning is currently the main task of an interdisciplinary NET center and preferably coordinated by an endocrinologist. Current data on the basis of recent studies do not allow any conclusions about the mean progression time, mean progression-free survival, prolonging the median progression-free interval, and the median time to renewed progression (1). On this background, prolonging the progression-free interval by only six months by means of new molecular therapies (2) is highly unsatisfactory and would presumably hardly be what the authors intended. The diagnosis of insulinoma in 2011 is based on the biochemical analysis of the unmistakable insulin secretion profile (3). This is recorded for 3–12 hours after glucose loading until neuroglucopenia. Without a secretion profile that is typical for an insulinoma, neuroglucopenia subsequently requires a selective intraarterial calcium injection test (SACI) (4). The 72 hour fasting test or C-peptide suppression test hardly helps to distinguish between patients with insulinoma and patients with pancreatic islet cell hyperplasia. Pathologists often refer to the latter as nesidioblastosis, whereas clinicians prefer the term non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Measuring proinsulin is vital, in contrast to measuring C-peptides. Testing for sulfonylureas is uncecessary; it implies that insulinoma patients are dissembling and also means that the indication was not clearly defined. In 30 years’ practice, we have never seen any reason to measure sulfonylureas, although we have diagnosed insulinoma in patients with a false-positive glibenclamide test result.

A Rare Case of Noninsulinoma Pancreatogenous Hypoglycemia Syndrome

As the obesity pandemic continues to worsen and medical interventions remain only moderately effective, bariatric surgery remains an important option for patients. In certain instances, patients who have undergone the procedure experience postprandial symptoms of neuroglycopenia caused by noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS). NIPHS is a recently described syndrome and is also very rare, and therapeutic approaches are still under debate. We report the case of a 51-year-old female who underwent Roux-en-Y gastric bypass and presented with episodic postprandial hypoglycemia 2 years after surgery. An insulinoma was absent from all abdominal imaging. Fasting C-peptide, insulin, and glucose were normal. Due to the possibility of NIPHS, clinical treatment was commenced with acarbose, leading to a significant reduction of hypoglycemic episodes. NIPHS occurs in approximately 0.5% to 7% of patients with hyperinsulinemic hypoglycemia. Sporadic hypoglycemia postgastric bypass is an important entity that should be understood by all surgeons and internists who are involved in postgastric bypass care.

NANETS Consensus Guidelines for the Diagnosis of Neuroendocrine Tumor

Neuroendocrine tumors (NETs) are rare, slow-growing neoplasms characterized by their ability to store and secrete different peptides and neuroamines. 1 Some of these substances cause specific clinical syndromes, 2 whereas other may have elevated plasma or urine levels that are not associated with specific syndromes or symptom complexes Unfortunately, there is no Bideal neuroendocrine tumor marker,[ 3 but according to the presentation, the sensitivity and specificity of each marker vary, and it is generally possible to choose those of greatest value for each clinical syndrome. The biochemical markers are those hormones or amines secreted by the neuroendocrine cells from which these tumors are derived. Some of these are not specific to any tumor, but are produced and secreted by most NETs, whereas other biochemical markers are more specific to the type of tumor and where their quantification can lead to the suspicion or confirmation of the presence of such a tumor. The annual incidence of NETs has risen to 40 to 50 cases per million, perhaps because of better diagnosis and the availability of highly specific and sensitive ways to measure these tumors’ products, improved immunohistochemistry, and enhanced techniques for tumor detection. Thus, the perceived increase in incidence may not be a real change in the incidence of the disease. There are a number of impediments to the diagnosis of these tumors. They are rare, comprising less than 2% of gastrointestinal (GI) malignancies, and are therefore not high on the list of causes of specific symptom complexes. Symptoms themselves are often nonspecific and do not lend themselves readily to identifying the specific underlying tumor. In addition, the manifestations are protean and mimic a variety of disorders. Tumors may be found incidentally on laparoscopy for abdominal pain or during the surgical removal of an appendix or even during a computerized tomographic scan of the abdomen for unexplained symptoms. Lung carcinoids may present with hemoptysis or asthma-like symptoms, and midgut carcinoids may be confused with irritable bowel syndrome (IBS). The natural history of this disease is invariably attended by a long history of vague abdominal symptoms, a series of visits to a primary care practitioner, and referral to a gastroenterologist, often with a misdiagnosis of IBS. These symptoms persist with a median latency to correct diagnosis of 9.2 years by which time the tumor has metastasized, causing symptoms such as flushing and diarrhea and progressing on its slow but relentless course until the patient dies. Clearly, a greater index of suspicion and a carcinoid tumor profile screen are warranted for all patients presenting with Btraditional IBS symptoms.[ Midgut carcinoids are associated with mesenteric fibrosis, which can compress mesenteric vessels and cause bowel ischemia and malabsorption, which may be found in the absence of an abdominal mass. The diagnosis of metastases to the liver is generally more obvious but often still takes place only after a delay of many years. Even then, an incorrect diagnosis is not uncommon. Unless biopsy material is examined for the secretory peptides chromogranin, synaptophysin, or neuron-specific enolase (NSE), tumors may be labeled erroneously as adenocarcinoma, with a negative impact on physician’s attitudes regarding management and underestimation of prospects for survival. 4 The common symptomatic manifestations of patients with carcinoid tumors are illustrated in Tables 1 and 2. Flushing

Hypoglycaemia following upper gastrointestinal surgery: case report and review of the literature

BackgroundHyperinsulinemic hypoglycemia is relatively recently recognized in persons undergoing bariatric surgery although knowledge and experience with this condition may not be commensurate with the number of such procedures being performed globally. This paper presents a novel case as an example of how such patients may present and how they may be investigated.Case PresentationA 69-year-old man was assessed 3 months post-fundoplication surgery for postprandial hypoglycaemia with neuroglycopenia that became progressively severe. A 72-h fast failed to show hypoglycaemia. During a clinic visit, the patient became confused and had a low plasma glucose, high plasma insulin, and high plasma C-peptide; symptoms were relieved with glucose. No tumours were visualized on CT, MRI, or endoscopic ultrasound. A total body Indium111-octreotide scan was negative. Selective arterial calcium stimulation showed a high insulin gradient in the splenic and superior mesenteric arteries, suggesting diffuse pancreatic beta cell hyperplasia. The patient declined pancreatic resection and recurrent symptomatic hypoglycaemia was successfully prevented with low dose octreotide.ConclusionsAlthough increasingly recognized following bariatric surgery, this is the first reported development of NIPHS (non-insulinoma pancreatogenous hypoglycemia syndrome) following fundoplication surgery, as well as the first documented use of octreotide in post-operative NIPHS. Medical management may be an alternative to surgery for patients with this rare condition.