Intraoperative segmental pancreatic occlusion and insulin assay combination optimizes the localization of lesions and confirmation of complete resection in pancreatic hypoglycemia patients.

AIM: To evaluate the efficacy of the application of intraoperative segmental pancreatic occlusion and insulin assay in surgical procedures for pancreatic hypoglycemia. METHODS: We retrospectively analyzed the clinical data of 11 pancreatic hypoglycemia cases treated in the China-Japan Friendship Hospital between September 2015 and August 2021. Intraoperative segmental pancreatic occlusion and insulin assay were used to enhance hypersecretory pancreatic tissues' localization and to achieve a complete resection. Intraoperative testing of insulin levels (peripheral venous blood) was carried out at several time points starting from before the resection of hypersecretory tissues (base value) and at 1 minute, 5 minutes, 15 minutes, 30 minutes, and 60 minutes after resection. Additional testing every 30 minutes until the end of the operation was carried out when necessary. RESULTS: A total of 11 pancreatic hypoglycemia cases were included; 9 cases were insulinomas (all with single pancreatic lesions, with 4 located in the head, 1 in the body, and 4 in the tail), 1 MEN-1, and 1 nesidioblastosis. The insulin assay (30 minutes after the resection of hypersecretory tissues) enhanced the ability to locate target tissues and the accuracy of complete resection to 100%. As for intraoperative blood glucose monitoring, the accuracy 30 minutes after resection was as low as 36.6%. Postoperative levels of insulin and glucose were normal in all patients, with no recurrence of hypoglycemic symptoms during postoperative follow-up visits (9 to 72 months). CONCLUSION: Intraoperative segmental pancreatic occlusion and insulin assay in pancreatic hypoglycemia is a simple, accurate, and fast approach that enhances the localization and complete resection of hypersecretory tissues. Such a combination is highly significant in challenging cases of hypoglycemia.

Homeostasis Model Assessment of ß-Cell Function for Diagnosis of Insulinoma.

CONTEXT: Diagnosis of insulinoma is based on different criteria from the 72-hour fasting test according to current guidelines (Endocrine Society [ES], European [ENETS], and North American [NANETS] Neuroendocrine Tumor Societies), including assessment of ß-cell function by glucagon stimulation test. OBJECTIVE: This study tested whether the homeostasis model assessment of insulin secretion, including assessment of ß-cell function, (HOMA-B) at the end of the fasting test provides comparable efficacy for insulinoma diagnosis. METHODS: In 104 patients with suspected insulinoma, 72-hour fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B values using insulin and C-peptide were calculated at the end of the fasting test, as defined by the lowest glucose concentration from each participant. RESULTS: HOMA-B was more than 6.5-fold higher in patients with (n = 23) than in those without (n = 81) insulinoma (insulin and C-peptide; both P < .001). HOMA-B (cutoff using insulin >253 a.u. and C-peptide >270 a.u.) had a sensitivity of 0.96, 0.78 to 1.00, and a specificity of 0.96 or greater (≥0.89-0.99) for insulinoma diagnosis. ES and ENETS/NANETS criteria reached a diagnostic sensitivity of less than or equal to 0.96 (≤0.78-1.00) and ≤0.83 (≤0.61-0.95) as well as specificity of ≤0.85 (≤0.76-0.92) and less than or equal to 1.00 (≤0.96-1.00) for insulin, and C-peptide, respectively. Using insulin for HOMA-B, sensitivity tended to be higher compared to ENETS/NANETS criteria (P = .063) and specificity was higher compared to ES criteria using insulin and C-peptide (both P < .005). CONCLUSION: HOMA-B, as calculated at the end of the fasting test employing defined cutoffs for insulin and C-peptide, provides excellent diagnostic efficacy, suggesting that it might represent an alternative and precise tool to diagnose insulinoma.

A review on nondiabetic hypoglycemia from various causes: Case series report.

RATIONALE: Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause harm to patients' cognition, consciousness, central nervous system, cardiovascular and cerebrovascular system, and even death. However, the most fundamental way to control hypoglycemia is to identify the cause and deal with the primary disease. This article introduces 3 cases of nondiabetic hypoglycemia with different causes, aiming to improve our understanding of nondiabetic hypoglycemia and improve the ability of early diagnosis and differential diagnosis. PATIENT CONCERNS: Case 1 is a 19-year-old female with a history of recurrent coma, and magnetic resonance imaging and endoscopic ultrasound of the pancreas suggest insulinoma. Case 2 is a 74-year-old male with a history of viral hepatitis, and computerized tomography shows multiple nodules in the liver, which is diagnosed as liver cancer. Case 3 is a 39-year-old female with a history of taking methimazole, who tested positive for insulin antibodies, and was diagnosed with insulin autoimmune syndrome. DIAGNOSIS: All 3 patients were diagnosed with nondiabetic hypoglycemia, but the causes varied, and included insulinoma, non-islet cell tumor-induced hypoglycemia, and insulin autoimmune syndrome. INTERVENTIONS: Case 1 underwent pancreatic tail resection; case 2 refused anti-tumor treatment and received glucose injections for palliative treatment only; and case 3 stopped taking methimazole. OUTCOMES: After surgery, the blood sugar in case 1 returned to normal, and the blood sugar in case 2 was maintained at about 6.0 mmol/L. The symptoms of hypoglycemia gradually improved in case 3 after stopping the medication. LESSONS: Non-diabetic hypoglycemia requires further examination to clarify the cause, and the correct differential diagnosis can provide timely and effective treatment, improving the patient's prognosis.

Evaluation of plasma cortisol during fasting test in patients with endogenous hyperinsulinemic hypoglycemia. Fifteen years experience.

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare clinical condition. The aim of this study was to evaluate baseline plasma cortisol concentration and its concentration during hypoglycemic crisis in fasting tests (FT) performed in our center. Secondarily, the aim was to establish the relationship between baseline cortisol and the time of evolution of EHH. MATERIAL AND METHODS: A retrospective, observational, descriptive study was carried out which included patients with hypoglycemic disorder with positive FT. RESULTS: Of a total of 21 patients, 16 presented insulinoma, 1 nesidioblastosis, 2 malignant insulinoma and 2 EHH without pathological diagnosis. The time from the onset of symptoms to diagnosis was 2 years (Q1=1.5-Q2=5.5). The comparison between median baseline cortisol (BC)=11.8 mcg/dl (nmol/L 340.68) (Q1=9-Q3=14.1) and median cortisol during hypoglycemic episode (HC)=11.6 mcg/dl (nmol/L: 303.44) (Q1=7.8-Q3=16.1) showed no differences (Z=-0.08; P>.05). When correlating BC with HC, no significant relationship was observed (r=0.16; P>.05). When correlating the glycemic value in the crisis and the HC, a slight negative trend was found (r=-0.53; P=.01). In addition, we found that recurrent hypoglycemic disorder is associated with lower baseline cortisol values ​​the longer the time of its evolution. CONCLUSION: We confirmed that cortisol values ​​remain low during hypoglycemic episodes, reinforcing the hypothesis of lack of response of this counterregulatory hormone in cases of recurrent hypoglycemia.

Synchronous Insulinoma and Glucagonoma: A Review of the Literature.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

Diagnosis and Surgical Management of Insulinomas-A 23-Year Single-Center Experience.

Background and Objectives: Insulinoma is a rare tumor of the Langerhans islets of the pancreas. It produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms. The incidence is low, at about 1-2 per 1 million inhabitants per year. The diagnosis is based on the presence of Whipple's triad and the result of a fasting test. Surgery is the treatment of choice. Objectives: A retrospective observational study of patients operated on for insulinoma in our hospital focused on the diagnosis, the type of surgery, and complications. Materials and Methods: We retrospectively reviewed patients operated on due to insulinoma. There were 116 surgeries between 2000 and 2022. There were 79 females and 37 males in this group. A fasting test and a CT examination were performed on all the patients. Results: The average duration of the fasting test was 18 h. Insulinoma was found in the body and tail of the pancreas in more than half of the patients. Enucleation was the most frequent type of surgery. Complications that were Clavien Dindo grade III or more occurred in 18% of the patients. The most frequent complications were abscesses and pancreatic fistula. Five patients had malignant insulinoma. Conclusions: Surgery is the treatment of choice in the case of insulinomas. The enucleation of the tumor is a sufficient treatment for benign insulinomas, which are not in contact with the main pancreatic duct. Due to the low incidence of the condition, the centralization of patients is recommended.

European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes.

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.

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

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

New Radiolabeled Exendin Analogues Show Reduced Renal Retention.

PET imaging of the glucagon-like peptide-1 receptor (GLP-1R) using radiolabeled exendin is a promising imaging method to detect insulinomas. However, high renal accumulation of radiolabeled exendin could hamper the detection of small insulinomas in proximity to the kidneys and limit its use as a radiotherapeutic agent. Here, we report two new exendin analogues for GLP-1R imaging and therapy, designed to reduce renal retention by incorporating a cleavable methionine-isoleucine (Met-Ile) linker. We examined the renal retention and insulinoma targeting properties of these new exendin analogues in a nude mouse model bearing subcutaneous GLP-1R-expressing insulinomas. NOTA or DOTA was conjugated via a methionine-isoleucine linker to the C-terminus of exendin-4 (NOTA-MI-exendin-4 or DOTA-MI-exendin-4). NOTA- and DOTA-exendin-4 without the linker were used as references. The affinity for GLP-1R was determined in a competitive binding assay using GLP-1R transfected cells. Biodistribution of [68Ga]Ga-NOTA-exendin-4, [68Ga]Ga-NOTA-MI-exendin-4, [177Lu]Lu-DOTA-exendin-4, and [177Lu]Lu-DOTA-MI-exendin-4 was determined in INS-1 tumor-bearing BALB/c nude mice, and PET/CT was acquired to visualize renal retention and tumor targeting. For all tracers, dosimetric calculations were performed to determine the kidney self-dose. The affinity for GLP-1R was in the low nanomolar range (<11 nM) for all peptides. In vivo biodistribution revealed a significantly lower kidney uptake of [68Ga]Ga-NOTA-MI-exendin-4 at 4 h post-injection (p.i.) (34.2 ± 4.2 %IA/g), compared with [68Ga]Ga-NOTA-exendin-4 (128 ± 10 %IA/g). Accumulation of [68Ga]Ga-NOTA-MI-exendin-4 in the tumor was 25.0 ± 8.0 %IA/g 4 h p.i., which was similar to that of [68Ga]Ga-NOTA-exendin-4 (24.9 ± 9.3 %IA/g). This resulted in an improved tumor-to-kidney ratio from 0.2 ± 0.0 to 0.8 ± 0.3. PET/CT confirmed the findings in the biodistribution studies. The kidney uptake of [177Lu]Lu-DOTA-MI-exendin-4 was 39.4 ± 6.3 %IA/g at 24 h p.i. and 13.0 ± 2.5 %IA/g at 72 h p.i., which were significantly lower than those for [177Lu]Lu-DOTA-exendin-4 (99.3 ± 9.2 %IA/g 24 h p.i. and 45.8 ± 3.9 %IA/g 72 h p.i.). The uptake in the tumor was 7.8 ± 1.5 and 11.3 ± 2.0 %IA/g 24 h p.i. for [177Lu]Lu-DOTA-MI-exendin-4 and [177Lu]Lu-DOTA-exendin-4, respectively, resulting in improved tumor-to-kidney ratios for [177Lu]Lu-DOTA-MI-exendin-4. The new exendin analogues with a Met-Ile linker showed 2-3-fold reduced renal retention and improved tumor-to-kidney ratios compared with their reference without the Met-Ile linker. Future studies should demonstrate whether [68Ga]Ga-NOTA-MI-exendin-4 results in improved detection of small insulinomas in close proximity to the kidneys with PET/CT. [177Lu]Lu-DOTA-MI-exendin-4 might open a window of opportunity for exendin-based radionuclide therapy.

Is hyperinsulinemia a possible clinical explanation underlying the myth of Erysichthon?

BACKGROUND: An insulinoma is an endocrine tumor of the pancreas, originating from the beta cells, and has a prevalence of 4 cases per 1 million patients. Insulinomas often follow a "90% rule": 90% are benign [1, 2], 90% originate in the pancreas, 90% are approximately 2 cm wide, and 90% are isolated. Individuals with an insulinoma may have episodic bouts of hyperinsulinemic hypoglycemia. Typically, an insulinoma is indicated by hypoglycemic symptoms which are a result of catecholamine reaction and neuroglycopenia. There is increased secretion of insulin in patients with an insulinoma despite having lower glucose levels. PURPOSE: This paper examines the myth of Erysichthon and speculates whether the symptoms experienced by him are possibly related to those found in patients with an hyperinsulinoma. METHODS: The myth of Erysichthon was taken from various sources (i.e. Hesiod, Callimachus, Ovid) and examined. Symptoms of Erysichthon were then examined. RESULTS: The myth of Erysichthon depicts various sympathoadrenal and neuroglycopenic symptoms including anxiety and abnormal behaviour which can be found in insulinomas. Insulinomas may often present a diagnostic challenge due to their deceptive nature and overlapping symptoms with other disorders such as neurologic disease. Insulinomas inducing weight loss resemble Calamachus's account of Erysichthon whose body is finally emaciated, even though having polyphagia. CONCLUSION: The myth of Erysichthon provides an interesting range of clinical symptoms which I have argued relate to symptoms found in patients with an insulinoma. Although, insulinomas were unknown in ancient medical lore, this paper has speculated that based on Erysichthon's symptoms, the possibility of an insulinoma cannot be ruled out.

Effective strategies for adequate control of hormonal secretion in functioning neuroendocrine neoplasms.

Neuroendocrine neoplasms are a unique form of malignancies as they can be accompanied by specific functioning hormonal syndromes that can impair survival and quality of life in patients. Functioning syndromes are defined by the combination of specific clinical signs and symptoms in combination with inappropriately elevated circulating levels of hormones. Clinicians should remain vigilant for the presence of functioning syndromes in neuroendocrine neoplasm patients at presentation as well as during follow-up. The correct diagnostic work-up should be initiated in cases of clinical suspicion of a neuroendocrine neoplasm-associated functioning syndrome. Management of a functional syndrome includes options from supportive, surgical, hormonal and antiproliferative treatment modalities. Here, we review the patient and tumour characteristics for each functioning syndrome that should be taken into account when deciding the optimum treatment strategy in neuroendocrine neoplasm patients.

Insulinoma in childhood: a retrospective review of 22 patients from one referral centre.

Background: Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1). Methods: We conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained. Results: A total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1-46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations. Conclusions: In this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.

Insulinoma as a cause of seizure-like activity and spontaneous hypoglycaemia.

A woman in her 60s presented to our hospital with recurrent episodes of confusion and double vision with spontaneous recovery to baseline within 10 min. Her initial workup was unremarkable, and she was diagnosed with complex partial seizures and commenced on levetiracetam. The following week, she re-presented with a recurrence of her symptoms, associated with spontaneous hypoglycaemia, with blood glucose levels of 1.9 mmol/L. She was found to have endogenously elevated serum insulin and C peptide levels, which were concomitantly associated with hypoglycaemia. An initial diagnosis of insulinoma was made and she was commenced on diazoxide. MRI and endoscopic ultrasound revealed 16 mm insulinoma in her uncinate process. She underwent surgical resection and remained symptom free at follow-up. This case highlights the importance of blood glucose measurements in patients presenting with neuroglycopenic symptoms and outlines the workup and management of insulinoma.

Clinical Presentation and Diagnostic Approach to Hypoglycemia in Adults Without Diabetes Mellitus.

OBJECTIVE: To review the clinical presentation, causes, and diagnostic approach to spontaneous hypoglycemia in adults without diabetes mellitus. METHODS: A literature review was performed using the PubMed and Google Scholar databases. RESULTS: Hypoglycemia is uncommon in people who are not on glucose-lowering medications. Under normal physiologic conditions, multiple neural and hormonal counterregulatory mechanisms prevent the development of abnormally low levels of plasma glucose. If spontaneous hypoglycemia is suspected, the Whipple triad should be used to confirm hypoglycemia before pursuing further diagnostic workup. The Whipple criteria include the following: (1) low levels of plasma glucose, (2) signs or symptoms that would be expected with low levels of plasma glucose, and (3) improvement in those signs or symptoms when the level of plasma glucose increases. Spontaneous hypoglycemia can be caused by conditions that cause endogenous hyperinsulinism, including insulinoma, postbariatric hypoglycemia, and noninsulinoma pancreatogenous hypoglycemia. Spontaneous hypoglycemia can also be seen with critical illness, hepatic or renal dysfunction, hormonal deficiency, non-diabetes-related medications, and non-islet cell tumors. The initial diagnostic approach should begin by obtaining a detailed history of the nature and timing of the patient's symptoms, medications, underlying comorbid conditions, and any acute illness. A laboratory evaluation should be conducted at the time of the spontaneous symptomatic episode. Supervised tests such as a 72-hour fast or mixed-meal test may be needed to recreate the situation under which the patient is likely to experience symptoms. CONCLUSION: We provide an overview of the physiology of counterregulatory response to hypoglycemia, its causes, and diagnostic approaches to spontaneous hypoglycemia in adults.

Case presentation of 8-year follow up of recurrent malignant duodenal Insulinoma and lymph node metastases and literature review of malignant Insulinoma management.

BACKGROUND: Insulinoma is an uncommon insulin-secreting neuroendocrine tumor that presents with severe recurrent hypoglycemia. Although cases of extrapancreatic insulinomas have been reported, the majority of insulinomas occur in the pancreas. The number of reported cases of ectopic insulinomas with follow-up assessments is limited and they do not report disease recurrence. The current report presents the first documented case of recurrent extrapancreatic insulinoma with 8 years of follow-up, provides relevant literature review, and proposes surveillance and treatment strategies. CASE PRESENTATION: We describe an insulinoma localized in the duodenal wall of a 36-year-old female who presented in 2013 with weight gain and Whipple's triad and was successfully managed with duodenotomy and enucleation. She presented again in 2017 with recurrent Whipple's triad and was found to have metastatic disease localized exclusively to peripancreatic lymph nodes. Primary pancreatic insulinoma was not evident and her hypoglycemia resolved following lymph node dissection. Eight years after initial presentation continuous glucose monitoring (CGM) showed a trend for euglycemia, and PET-CT Gallium 68 DOTATATE scan evaluation indicated absence of recurrent disease. CONCLUSION: Insulinomas are rare clinical entities and extrapancreatic insulinomas are particularly uncommon. Follow-up evaluation and treatment strategies for ectopic insulinoma recurrence presents a significant clinical challenge as the condition has hitherto remained undescribed in the literature. Available evidence in the literature indicates that lymph node metastases of intrapancreatic insulinomas likely do not change prognosis. Given the absence of long-term data informing the management and monitoring of patients with extrapancreatic insulinoma, we suggest patient education for hypoglycemic symptoms, monitoring for hypoglycemia with CGM, annual imaging, and a discussion with patients regarding treatment with octreotide or alternative somatostatin receptor analog therapies.

Blood glucose monitoring during surgery in dogs to assess completeness of surgical resection of insulinoma: 11 cases.

OBJECTIVE: To evaluate whether intraoperative detection of rising levels of blood glucose could improve the completeness of resection of insulin-secreting tumor tissue and whether this improves long-term outcomes. ANIMALS: 11 client-owned dogs diagnosed with insulinoma. PROCEDURES: Retrospective review of medical records of dogs undergoing partial pancreatectomy as treatment for insulinoma. A blood glucose reading was obtained at induction, following removal of the pancreatic mass and/or after each suspected metastatic lesion until blood glucose had normalized. Disease-free interval and survival time were measures of outcome. RESULTS: A positive increase in blood glucose was detected in all cases, with a mean rise of 6.35 ± 4.5 mmol/L. Mean follow-up was 611 days, mean disease-free interval was 382 days, and median survival time was 762 days. Tumor stage was not associated with outcome. Three cases underwent a second surgery (metastasectomy), achieving further prolongation of disease-free survival. CLINICAL RELEVANCE: A sustained increase in intraoperative blood glucose provided the surgeon with confidence of more complete resection of insulinoma tissue and resulted in improved outcomes in all cases included in this study. Subsequent metastasectomy of recurrent insulinoma lesions also provided good outcomes. Intraoperative monitoring of blood glucose during surgical treatment of insulinoma resulted in the surgeon continuing to explore and resect abnormal tissue until an increase of glycemia was observed. This was shown to provide the surgeon with more confidence of resection of all active insulinoma tissue and improved clinical outcomes.

Functional Insulinomas in a Rhesus Macaque (Macaca mulatta).

We report a rare case of functional insulinomas in a 16.7-year-old female Rhesus macaque (Macaca mulatta) that was presented with neuroglycopenic signs to the breeding colony hospital at the Tulane National Primate Research Center. At initial and follow-up examinations, the animal was consistently hypoglycaemic and was clinically maintained with additional fruits, other high-sugar food items and dextrose supplementation. Occasional episodes of seizure and collapse resolved quickly on administration of high-sugar food items. At necropsy, the uncinate process of the pancreas had a 2.2 cm diameter, red, round, firm neoplastic mass, and another neoplasm was identified on histological examination of the head of pancreas. Histologically, neoplastic cells exhibited neuroendocrine packeting, resembled pancreatic islet cells and immunolabelled for chromogranin A, synaptophysin and insulin but not for somatostatin, gastrin or pancreatic polypeptide. A few cells immunolabelled for glucagon. The clinical signs and gross and histological findings were consistent with functional insulinomas.

Varied presentations of pancreatic insulinoma: a case report.

An insulinoma is a rare functional pancreatic neuroendocrine tumour that is usually sporadic and solitary. The hallmark is hypersecretion of insulin, which leads to neuroglycopenia symptoms and uncontrolled sympathoadrenal activity. Neuroendocrine tumours can have a varied presentation, with symptoms often ascribed to a different diagnosis, thus delaying correct diagnosis and treatment. We present the case of a 26-year-old female who had a 3-year delay before diagnosing insulinoma after being initially assessed with epilepsy and schizophrenia. The case report below provides a detailed review of the diagnosis, tumour localization, and surgical interventions implemented for the patient during the COVID-19 pandemic.

Insulinoma mimic: methadone-induced hypoglycaemia.

Methadone use for opioid use disorder and chronic pain has increased since the start of the century with about 4.4 million dispensed prescriptions in 2009. With increased use of methadone, there has been increasing reporting of less commonly reported side effects (ie, hypoglycaemia). Here, we describe a woman in her 70s with history of opioid use disorder on methadone, stage 4 chronic kidney disease and prior hypoglycaemic episodes who initially presented with perforated gastric ulcer requiring surgical repair. Her perioperative course was complicated by profound hyperinsulinaemic hypoglycaemia. Given concern for methadone-induced hypoglycaemia, methadone was discontinued with monitoring of subsequent blood glucose, insulin, C peptide, proinsulin, ß-hydroxybutyrate and blood methadone levels. As the serum methadone levels decreased, insulin levels substantially decreased in parallel. After 21 days off methadone, dextrose infusion was discontinued with restoration of euglycaemia. In a patient with hyperinsulinaemic hypoglycaemia and methadone use, it is important to consider discontinuing methadone and re-evaluate fasting glucose levels prior to an extensive and invasive insulinoma workup.