Search

Gastroenteropancreatic neuroendocrine tumours (GEP‐NETs), which may be hormone secreting (e.g., gastrinomas and insulinomas) or non‐secreting (also known as non‐functioning NETs) are associated with severe morbidity and have a median overall survival of 75–124 months. Studies have highlighted the importance of epigenetic mechanisms in GEP‐NETs pathogenesis, with the most frequently mutated genes being the epigenetic regulators, MEN1, DAXX, and ATRX. However, the consequences of these aberrant epigenetic mechanisms are poorly understood. The calcium sensing receptor (CASR), a G protein coupled‐receptor, is epigenetically silenced in cancers, and therefore we examined its role in GEP‐NET subtypes. Using RNA‐Scope and quantitative PCR analyses in two independent tumour cohorts from Europe (n = 18 patients) and the USA (n = 46 patients) we showed that CASR mRNA is almost completely absent in gastrinomas, insulinomas and non‐functioning pancreatic NETs. Furthermore, immunohistochemical staining confirmed a significant reduction in CaSR protein expression in all GEP‐NET subtypes, compared to normal islets. DNA methylationEPIC and ATAC‐seq analyses in the pancreatic NET cell line QGP‐1 showed the CaSR promoter was both hypermethylated and in a region of closed chromatin. Furthermore, transfection of wild type CaSR into QGP‐1 cells decreased cell viability, in keeping with the CaSR having a role in cellular proliferation. In summary, our study reveals that CaSR expression is decreased in GEP‐NETs and that this reduced expression is likely due to DNA methylation and chromatin changes. Moreover, we demonstrate that transfection of the CaSR into a PNET cell line reduces cell viability, thereby indicating that the CaSR acts as a tumour suppressor in this tumour type. [ABSTRACT FROM AUTHOR] more...

Functioning pancreatic neuroendocrine tumors (PanNETs) represent a subset of PanNETs that cause symptoms due to hormonal activity. Insulinoma is the most common functioning PanNET type. Mutations in the alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes result in genomic instability. ATRX/DAXX mutations and associated alternative lengthening of telomeres (ALT) are common in non-functioning PanNETs and associated with aggressive tumor behavior. Recent reports have shown that ATRX/DAXX mutations and ALT are also present in functioning PanNETs. In this review, we summarize the literature addressing ATRX/DAXX mutations and ALT in functioning PanNETs and discuss the clinical relevance with regard to distinguishing aggressive and indolent functioning tumors. ATRX/DAXX gene mutations and/or ALT have been reported in insulinoma, glucagonoma, gastrinoma, VIPoma and calcitoninoma. In insulinoma, the presence of ATRX/DAXX mutations and ALT are associated with aggressive behavior and could therefore be used as prognostic biomarkers. Although ATRX/DAXX mutation and ALT assessment may currently not be the standard of care in routine diagnostic pathology practice, the use of DAXX/ATRX immunohistochemistry at least can be encouraged not only for non-functioning but also for functioning PanNETs. [ABSTRACT FROM AUTHOR] more...

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Pancreatic neuroendocrine neoplasms (pNENs) represent approximately 2% of all solid pancreatic tumors. The incidence of pNENs has been increasing in the last decade. The clinical manifestations of pNENs range from hormone secretion syndromes in functioning neoplasms (F-pNENs) to local infiltration or distant metastases in late-stage diagnoses or incidental findings in small non-functioning neoplasms (NF-pNENs). While surgery is the gold-standard treatment for larger and more aggressive tumors, small and low-grade tumors (G1) may be followed-up due to the indolent course of disease. Recently, endoscopic ultrasound (EUS)-guided ablative techniques, such as ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA), have emerged as promising options for loco-regional ablations in selected cases. Despite promising safety profile and efficacy, high-quality evidence is needed to support their widespread adoption. This article reviews the current state of EUS-guided locoregional therapies, patient selection criteria, procedural details, and associated risks. [ABSTRACT FROM AUTHOR] more...

Insulinomas are rare neuroendocrine neoplasms and causes of hypoglycemia. They present with neuroglycopenic symptoms, including confusion and seizures. Suspected diagnosis must be confirmed through bloodwork and imaging. The majority of insulinomas are benign and cured surgically; less than 10% of insulinomas are malignant. Malignant insulinomas present a unique and rare challenge in managing persistent hypoglycemia and tumor burden. We present a case of a young woman who presented with Whipple triad and high-grade masses in her pancreas, liver, and distant lymph node metastases on imaging. Insulinoma was diagnosed. Hypoglycemia was managed with continuous dextrose infusion, diazoxide, and lanreotide. She was discharged on medical management and a continuous glucose monitor. Her metastatic disease is being treated with a capecitabine and temozolomide (CAPTEM) regimen showing 30% reduction in tumor burden. In conjunction with the National Institutes of Health, she is undergoing evaluation with numerous neuroendocrine tumor surgeons for cytoreductive surgery. [ABSTRACT FROM AUTHOR] more...

Background: Hypoglycemia in the case of persons without diabetes is a rare event, being usually, initially misinterpreted based on the symptoms that can mimic various diseases, especially of a neuro-psychiatric nature. In the case of the identification of insulin-mediated hypoglycemia, the evaluation of pancreatic neuroendocrine tumors, which represent the most common and worrisome causes of non-diabetic insulin-mediated hypoglycemia, must be considered. Case Report: We present the case of a 57-year-old patient, hospitalized for a history of approximately one month of recurrent episodes of symptoms suggestive for severe hypoglycemia. The biological evaluation performed during an episode of hypoglycemia showed a plasma glucose value of 44 mg/dL, insulinemia 16.3 µU/mL, C peptide 3.72 ng/mL, HbA1c 4.99%, absence of urinary ketone bodies and anti-insulin antibodies <0.03 U/mL. The CT and MRI examination showed a 15.3/15 mm rounded tumor in the pancreatic corporeo-caudal region. The pancreatic tumor formation was enucleated and the histopathological and immunohistochemical analysis confirmed the diagnosis of the pancreatic neuroendocrine tumor with a positive reaction for chromogranin A, synaptophysin and insulin, without malignancy features (Ki 67 positive in 1% of the tumor cells). The postoperative evolution was favorable, without episodes of hypoglycemia, the fasting insulinemia one day after surgery being 4.1 µU/mL and HbA1c at three weeks postoperatively being 5.51%. Conclusions: The management of patients with hyperinsulinemic hypoglycemia secondary to insulinoma involves multidisciplinary collaboration with an important role in recognizing symptoms suggestive of hypoglycemia in a person without diabetes, initiating biological and imaging evaluation, establishing the optimal therapeutic option and histopathological confirmation. [ABSTRACT FROM AUTHOR] more...

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him. [ABSTRACT FROM AUTHOR] more...

A 75-year-old female presented with fasting hypoglycemic episodes. A supervised fast ended at 72 hours fulfilling Whipple triad, with suppressed insulin and C-peptide levels, but discordantly suppressed serum β-hydroxybutyrate levels. After 21 months of recurring symptoms, a repeat fast ended at 48 hours with Whipple triad, suppressed serum β-hydroxybutyrate level, and borderline nonsuppressed C-peptide level, suggesting endogenous hyperinsulinism. Serum insulin levels were discordantly suppressed. Computed tomography (CT) of the abdomen demonstrated an enhancing 1.36 × 0.93-cm nodule in the head of the pancreas. Endoscopic ultrasound (EUS)-guided fine-needle aspirate of the lesion derived cytology consistent with a neuroendocrine tumor, but fine-needle core biopsy returned normal pancreatic tissue. Because the results were equivocal, functional imaging with 68Gallium-DOTA-exendin-4 positron emission tomography CT was performed, which confirmed the diagnosis of a single head-of-pancreas insulinoma. The patient declined surgical resection. Oral diazoxide therapy resulted in significant peripheral edema. Hence, EUS-guided radiofrequency ablation of the lesion was performed, and the patient remains symptom free 10 months postprocedure. This case illustrates that (1) exendin-4–based positron emission tomography may help one confidently diagnose and localize insulinoma when prior biochemical or endoscopic biopsy results are ambiguous; and (2) EUS-guided radiofrequency ablation is an efficacious alternative option to surgical resection in the frail, elderly patient with insulinoma. [ABSTRACT FROM AUTHOR] more...

In the past 2–3 decades, numerous attempts have been made to create an insulin‐secreting β cell line that maintains normal insulin secretion. However, primary β cell cultures have finite life and, therefore, cannot be used for long‐term experiments. The most widely used insulin‐secreting cell lines are Insulinoma‐1, rat insulinoma cell line, hamster pancreatic β cell line, mouse insulinoma, and β tumor cell line. Insulinoma‐derived cell lines show infinite growth in tissue culture but exhibit varying differences in their insulin responsiveness to glucose levels compared to normal β cells. Despite difficulties with β cell cultures, these cell lines have offered some useful insights in diabetes research concerning physiological functions and pathological investigations. In this review, we describe insulinoma cell lines used for drug screening, insulin secretion, cell viability, proliferation, and other relevant cellular functions. In addition, we have also incorporated recently developed human β cell lines. These cell lines have provided some helpful insights into physiological activities and pathology in diabetes research, despite challenges with β cell culturing. We propose that these cell lines could also be explored for screening Ayurvedic Rasayanas and homeopathy preparations for their cytotoxicity and insulin secretagogue activities to have evidence‐based data on alternative and complementary medicines. The easy availability of insulinoma and human β cell lines has facilitated diabetes research in understanding mechanism of action and cytotoxicity of drugs. This review summarizes the applications of existing insulinoma cell lines of rodent origin and newly developed human β cell lines. We highlight the importance of these in examining the cytotoxicity and insulin secretagogue activities of various drugs. Further, we propose that these cell lines could be used as a screening tool for Ayurvedic Rasayanas and homeopathy preparations. [ABSTRACT FROM AUTHOR] more...

Background/Objective: Evidence on the efficacy and safety of minimally invasive treatment for insulinoma has increased over the past decade to the point of becoming a recommendation in clinical practice guidelines for the management of this type of neuroendocrine tumor. Case Report: We describe the case of an elderly male patient with multiple comorbidities and recurrent isolated insulinoma of 3.7 × 3.5 cm involving the uncinate process of the pancreas and contacting the splenomesenteric confluent many years after first resection, in whom, after refusing surgical management, was performed as successful arterial embolization of the pancreatic tumor. Discussion: When addressing this pathology, it is common to encounter patients who are not candidates for surgical management, either due to the presence of comorbidities, the location of the tumor in relation to vascular structures, or refusal of the intervention. Therefore, it is important to be aware of the different therapeutic options in localized and metastatic disease. Conclusion: Minimally invasive procedures are positioned as an effective alternative for the treatment of the hormonal overproduction in patients with insulinoma. more...

Introduction: Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes. Methods: We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: ‘insulinoma’, ‘diabetes’, ‘nesidioblastosis’, ‘endogenous hyperinsulinism’, ‘hypoglycaemia’, and ‘hyperglycaemia’ (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods. Results: Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17–96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%–8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis. Conclusion: This first systematic review provides insights into the uniqueness of insulinoma in diabetes. more...

Background: Insulinoma is a neuroendocrine tumor (NET), with its main clinical manifestation being the hypoglycemic syndrome. The symptoms of hypoglycemia are nonspecific, and therefore, in most cases, the diagnosis is made untimely. The Russian clinical guidelines for the diagnosis and treatment of NET suggest as a diagnostic test that the universal circulating marker of all NET, chromogranin A (CgA) be determined. However, the literature data on the sensitivity of CgA in the diagnosis of insulinoma are contradictory. Aim: To evaluate the diagnostic effectiveness of the CgA test in the diagnosis of insulinoma. Materials and methods: This was a hospital-based single-center, cross-sectional comparative (first step) and prospective non-comparative (second step) study conducted from 2016 to 2022. During the first part of the study, we determined serum CgA in 120 patients with suspected non-diabetic hypoglycemia and compared its levels in the patients with and without confirmed insulinoma (n = 87 and n = 33, respectively). During the second study step, CgA was measured in the insulinoma patients at 6 [4.0; 7.0] months after surgery. The CgA levels at baseline and post-surgery were analyzed in 74 patients (those with recurring non-diabetic hypoglycemia were excluded from the analysis). Results: In the study subjects without insulinoma, the median CgA level was 0.7 [0.5; 1.1] (range, 0.1 to 2.0) nmol/l and the difference (with Bonferroni adjustment) from its levels in the patients with insulinoma before surgery was non-significant (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, р = 0.045). The CgA concentration in the insulinoma patients after surgery was 0.9 [0.7; 1.2], range, 0 to 1.9 nmol/l and significantly differed from that at baseline (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, p = 0.012, Wilcoxon test). In the patients with insulinoma before surgery the CgA levels exceeding the generally accepted reference range ( 2 nmol/l) was found in 11.5% (n = 10), with its median level of 2.5 [2.3; 4.1], range 2.3 to 8.5 nmol/l. There were no significant associations between the CgA levels and localization, tumor numbers, their size and malignization grade, insulin and proinsulin values, and duration of fasting. The sensitivity and specificity of the CgA test were 12% [95% confidence interval [CI]: 6%–20%] and 100% [95% CI: 97%–100%], respectively. The prognostic value of a positive result (PVPR) was 100% [95% CI: 69%–100%] and the prognostic value of a negative result (PVNR) 30% [95% CI: 28%–32%]. Conclusion: As a diagnostic test, CgA has high specificity and prognostic value of a positive result. However, the uncertainty of the prognostic value of a negative result is unacceptably high. A special study is required to clarify the operational characteristics of CgA in insulinoma. more...

Abstract Pancreatic neoplasm, a highly aggressive and often fatal cancer, poses challenges due to late detection and nonspecific symptoms. Therefore, both early diagnosis and appropriate therapeutic approaches are necessary to augment the condition of these patients. Cancer cells undergo metabolic deregulation, which enables their proliferation, survival, and invasion. As a result, it is crucial to focus on the metabolic pathways in prevalent cancers and explore treatment strategies that target these pathways to control tumor growth effectively. This is particularly relevant in cancers like pancreatic cancer, which undergo numerous metabolic alterations. The ketogenic regimen, characterized by low carbohydrate and protein contents and high-fat sources, does not involve caloric restriction. This allows for the induction of ketogenesis and an increase in ketone bodies, while insulin and glucose levels remain low even after meals. This unique metabolic state may influence the tumor microenvironment. Given the lack of unanimous agreement on the precise role and mechanism of the ketogenic diet, this review aims to clarify the diagnostic value and accuracy of ketone bodies in various types of pancreatic tumors and explore the potential anti-cancer effects of the ketogenic diet when used alone or in conjunction with chemotherapy, also to determine the potential of the ketogenic diet to be used as adjuvant therapy. The outcomes of this study are instrumental in enhancing our understanding of the benefits and drawbacks associated with employing this diet for the management and diagnosis of pancreatic cancer. Graphical Abstract more...

Insulinoma is a relatively uncommon pancreatic neuroendocrine tumor, with approximately 10% of the cases being malignant. Diabetes mellitus (DM) with concurrent insulinoma is very rare and the diagnosis of such condition is easily missed as it can be misconstrued as improved glycemic control. Therefore, persistent hypoglycemic symptoms even after stopping antidiabetic medications may be considered for insulinoma. Herein, we present a patient with DM and pancreatic insulinoma with extensive hepatic and skeletal metastases on dual-tracer positron emission tomography/computed tomography (PET/CT) ([68Ga]Ga-DOTATATE and [18F]fluorodeoxyglucose). Given the extensive disease, the patient was treated with a combination of peptide receptor radionuclide therapy (PRRT) and chemotherapy (capecitabine and temozolomide). During therapy, patient showed early clinical and imaging response for insulinoma leading to unmasking of poor glycemic control necessitating requirement of insulin administration for DM. The patient did not experience any life-threatening hypoglycemia during the chemo-PRRT treatment and showed an improvement in quality of life. Unfortunately, the disease progressed at the 4th cycle, 10 months after the initiation of PRRT. We conclude that combined chemo-PRRT may be considered an effective treatment option for patients with metastatic insulinoma and DM owing to its favorable imaging response and effective symptom control. [ABSTRACT FROM AUTHOR] more...

Functional pancreatic neuroendocrine tumors (pNET) necessitate surgical resection. Enucleation is the preferred surgical method for well-differentiated pNETs that measure less than 2 cm in diameter, as it offers a greater likelihood of enhancing post-operative recovery and decreasing morbidity and mortality. Insulinomas are particularly suitable for enucleation when such a procedure is viable. However, enucleating tumors within the uncinate process of the pancreas, especially on its posterior aspect, can present substantial challenges. The accompanying video illustrates a robotic-assisted enucleation of an insulinoma in the uncinate process, performed on a 41-year-old male with recurrent hypoglycemia. This intervention led to the resolution of symptoms and incurred minimal post-operative morbidity. [ABSTRACT FROM AUTHOR] more...

Simple Summary: Insulinomas are the most common tumors of the endocrine pancreas in dogs, often resulting in severe hypoglycemia and neurological symptoms. Surgical resection has been the traditional treatment, but it poses significant risks. This study explores the use of ultrasound-guided radiofrequency ablation (RFA) as a safer and less invasive alternative. RFA was found to effectively control glucose levels and reduce tumor size in most treated dogs while reducing recovery times and complications. These findings suggest that RFA offers a valuable treatment option for managing insulinomas and their metastasis in canine patients. Insulinomas are the most common neoplasms of the endocrine pancreas in dogs, leading to persistent hypoglycemia due to inappropriate insulin secretion. The standard treatment is surgical resection, but it carries significant risks, including pancreatitis and diabetes mellitus. This study investigates the efficacy and safety of percutaneous ultrasound-guided radiofrequency ablation (RFA) as an alternative to surgery. A total of 29 dogs diagnosed with insulinoma were treated with RFA, targeting both primary pancreatic tumors and metastases in regional lymph nodes or the liver. Blood glucose levels and tumor size were monitored before and after the procedure. RFA led to a significant increase in blood glucose levels and a reduction in tumor size in all patients, with minimal postoperative complications. The results suggest that RFA is a feasible and effective treatment option for insulinomas in dogs. [ABSTRACT FROM AUTHOR] more...

Pancreatic neoplasm, a highly aggressive and often fatal cancer, poses challenges due to late detection and nonspecific symptoms. Therefore, both early diagnosis and appropriate therapeutic approaches are necessary to augment the condition of these patients. Cancer cells undergo metabolic deregulation, which enables their proliferation, survival, and invasion. As a result, it is crucial to focus on the metabolic pathways in prevalent cancers and explore treatment strategies that target these pathways to control tumor growth effectively. This is particularly relevant in cancers like pancreatic cancer, which undergo numerous metabolic alterations. The ketogenic regimen, characterized by low carbohydrate and protein contents and high-fat sources, does not involve caloric restriction. This allows for the induction of ketogenesis and an increase in ketone bodies, while insulin and glucose levels remain low even after meals. This unique metabolic state may influence the tumor microenvironment. Given the lack of unanimous agreement on the precise role and mechanism of the ketogenic diet, this review aims to clarify the diagnostic value and accuracy of ketone bodies in various types of pancreatic tumors and explore the potential anti-cancer effects of the ketogenic diet when used alone or in conjunction with chemotherapy, also to determine the potential of the ketogenic diet to be used as adjuvant therapy. The outcomes of this study are instrumental in enhancing our understanding of the benefits and drawbacks associated with employing this diet for the management and diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR] more...

Key Clinical Message: This case highlights the possibility of an insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression. Insulinoma is a pancreatic disease that causes hyperinsulinemic hypoglycemia. The first‐line treatment is surgery; however, somatostatin derivatives are administered in cases where surgery is not a viable option and to prevent preoperative hypoglycemia. Here, we report a case in which preoperative examination indicated a potential tumor with low somatostatin receptor 2 (SSTR2) and SSTR5 expression, whereas postoperative pathological examination indicated strong SSTR expression. We report the case of a 69‐year‐old Japanese female who experienced hypoglycemia‐like symptoms for a decade such as sweating, fatigue, hunger, and confusion with an increase in episode frequency per year. Dynamic computed tomography revealed a 13‐mm diameter nodule and aberrant blood flow in the pancreatic tail. Subsequently, the patient was diagnosed with pancreatic insulinoma. A preoperative octreotide test did not relieve hypoglycemia, and no uptake of 111indium‐pentetreotide was observed, suggesting an insulinoma with low SSTR expression. However, postoperative histological studies suggested that the intracellular domain of SSTRs were highly expressed, while the extracellular domain may be mutated. We present a rare case of insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression. [ABSTRACT FROM AUTHOR] more...

We report a case of a 35–year-old woman with recurrent episodes of hypoglycemia. Biochemical investigation was suggestive of hyperinsulinemic hypoglycemia, and hence a provisional diagnosis of insulinoma was made. Despite extensive investigation using magnetic resonance imaging, endoscopic ultrasound, and 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) scanning, the tumor could not be localized. Long-distance travel allowed her to undergo a 68Ga-Exendin-4 PET/CT scan that identified a lesion in the uncinate process of the pancreas, subsequently confirmed by intraoperative ultrasound. Enucleation of the 1.5-cm lesion was performed, and histopathology confirmed a well-differentiated pancreatic neuroendocrine tumor. Postoperatively, the patient has remained free of hypoglycemic episodes and has shown normalization of glucose levels. This case underscores the efficacy of 68Ga-Exendin-4 PET/CT in the localization of an occult insulinoma, facilitating timely and curative surgical intervention, and the importance of patients having access to such a facility when not locally available. [ABSTRACT FROM AUTHOR] more...

Objective: In recent years, endoscopic ultrasound‐guided radiofrequency ablation (EUS‐RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long‐term follow‐up of patients treated with EUS‐RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence. Design, Patients and Measurements: We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS‐RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow‐up was planned at 3, 6, 12 months and then annually. Results: In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow‐up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS‐RFA session was performed in one patient and the other patient is being closely monitored. Conclusions: EUS‐RFA treatment of benign insulinomas provides a long‐term complete clinical resolution of hypoglycaemia. A long‐term follow‐up is essential if residual tumour persists after initial EUS‐RFA treatment. [ABSTRACT FROM AUTHOR] more...

Background: Insulinomas are rare insulin-secreting neuroendocrine neoplasms of the pancreas. First-line treatment is the surgical removal of the tumor, however, the localization with standard imaging techniques is often challenging. With the help of selective intraarterial calcium stimulation the insulinoma's localization can be narrowed down to one third of the pancreas which the selected artery supplies. Objective: We aimed to prove the usefulness of the calcium stimulation test in case of 9 patients treated between 2006 and 2021 diagnosed with endogenous hyperinsulinemic hypoglycemia confirmed by fasting test, where conventional imaging methods, like transabdominal ultrasound, CT or MRI failed to detect the source of hyperinsulinemia. Methods: We performed selective intraarterial calcium stimulation with angiography with calcium gluconate injected to the main supporting arteries of the pancreas (splenic, superior mesenteric and gastroduodenal arteries); blood samples were obtained from the right hepatic vein before, and 30, 60 and 120 seconds after calcium administration. Results: With selective angiography we found a significant elevation of insulin levels taken from the right hepatic vein in five of the nine cases. On histopathology, the lesions were between 1-2 cm, in one case malignancy was also confirmed. In four patients we found a significant rise of insulin levels obtained from all catheterized sites, which confirmed the diagnosis of nesidioblastosis. In three cases no surgery was performed, and the symptoms relieved with medical treatment. Conclusions: Selective intraarterial calcium stimulation remains an important tool in localization of the source of insulin excess, especially in cases where other diagnostic modalities fail. [ABSTRACT FROM AUTHOR] more...

Introduction: Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes. Methods: We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: 'insulinoma', 'diabetes', 'nesidioblastosis', 'endogenous hyperinsulinism', 'hypoglycaemia', and 'hyperglycaemia' (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods. Results: Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17–96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%–8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis. Conclusion: This first systematic review provides insights into the uniqueness of insulinoma in diabetes. [ABSTRACT FROM AUTHOR] more...

Pancreatic masses are extremely rare in pediatric patients, with limited data available. This lack of data makes the diagnosis and management of these tumors in children extremely challenging. Therefore, we aimed to describe the presentations, clinical course, and outcomes of children with pancreatic tumors at our center. A retrospective analysis was performed of all pediatric patients diagnosed with pancreatic masses between 2003 and 2022 in an academic freestanding children's hospital. Data including demographics, clinical presentation, workup, management, and subsequent morbidity and mortality were collected and aggregated. Furthermore, we reviewed cases of pancreatic tumor resections in the National Surgical Quality Improvement Program – Pediatric (NSQIP-P) database to identify common adverse outcomes and measures for quality improvement. In total, 17 patients were identified at our institution. Diagnoses included solid pseudopapillary (n = 9), gastrinoma (n = 1), rhabdomyosarcoma (n = 2), pancreatoblastoma (n = 2), and insulinoma (n = 1). Two patients did not have a histopathologic diagnosis and were excluded from subsequent analysis. Overall, 12 patients underwent surgical intervention, with the most common procedures being pancreaticoduodenectomy and distal pancreatectomy, and all 12 were known to be alive at last contact. There were 3 deaths, all due to complications related to metastatic disease. Furthermore, 30-day postoperative outcomes in the NSQIP-P dataset for pancreatic surgeries in pediatric patients are excellent, with negligible morbidity and no mortalities after the index surgery. Conclusions: Children with pancreatic tumors amenable to surgical resection appear to have adequate long-term survival. Short-term outcomes at diagnosis are excellent and mainly appear to be influenced by the presence of metastatic disease at initial presentation. What is Known: • Pancreatic masses are a rare entity in children with limited data on their presentation, management and surgical outcomes. • Solid Pseudopapillary tumors are one of the most common pancreatic tumors in children with a fair prognosis after surgical intervention. What is New: • Surgical management of pediatric patients with pancreatic tumors is safe and effective in patients who do not have aggressive tumor types or metastatic disease. • Our case series provides a notable cohort of these pancreatic tumors with insight into the presentation, management and outcomes of five of these tumor types. [ABSTRACT FROM AUTHOR] more...

Endoscopic ultrasound-guided local ablation therapy is one of the most important approaches for treating insulinomas that arise from neuroendocrine islet cell tumors located within the pancreas. This study aimed to evaluate the efficacy of various ablative treatments including anhydrous ethanol, lauromacrogol, polidocanol, and paclitaxel as local ablative agents on subcutaneous insulinoma tumors in mice models using tumor necrosis and drug distribution. For this purpose, mice were modeled for insulinoma tumors by subcutaneous injection of Ins-1 and Min-6 cell lines in 4-6 weeks-old nude female mice. The tumors became visible 1 to 2 weeks after the transplantation of cells, reaching a treatment-appropriate volume of 20-30mm3 within 2 to 3 weeks, as confirmed by the insulinoma-like characteristics observed during histopathological analysis. The results indicated that the insulinoma animal models exhibited an early onset of hypoglycemia and significantly elevated serum insulin levels during starvation tests, compared to the control group further confirmed by expression of chromogranin A (CgA), synaptophysin (Syn), and insulinoma-associated protein 1 (Insm1) in the tumor cells during immunohistochemical staining. Following treatment, necrosis percentages in insulinoma tumors were significantly higher in the paclitaxel (93.2%) and ethanol (86.5%) groups compared to saline, polidocanol, and polyglactin groups. Similarly, tumor drug distribution was tracked using methylene blue, with paclitaxel demonstrating the fastest diffusion, followed by ethanol, polidocanol, and polyglactin. These findings suggest that both paclitaxel and polidocanol have significant potential as local ablative agents in inducing tumor necrosis, with paclitaxel offering the fastest drug dispersion. These results highlight the potential for further optimization of ablation therapies in insulinoma treatment. [ABSTRACT FROM AUTHOR] more...

Insulin-producing pancreatic tumors are a common subtype of neuroendocrine tumor. Standard of care includes surgical resection of the pancreatic tumor and medical management with somatostatin analogs. For patients with metastatic disease, tumor control and hypoglycemic symptom relief can be achieved through surgical resection of the tumor, hepatic artery embolization, radiofrequency ablation, or radioembolization using radioactive isotopes as well as with systemic therapy such as somatostatin analogs and everolimus. We present the case of a 74-year-old male with metastatic insulin-producing pancreatic carcinoma. After a long history of successfully controlling his hypoglycemic episodes post-liver wedge resection, bland embolizations subsequently failed to maintain control of the frequency and severity of his hypoglycemic symptoms. Stereotactic body radiotherapy (SBRT) with protons was used to achieve symptomatic control and led to partial radiographic response with complete resolution of his hypoglycemic episodes. This case demonstrates the potential utility of proton SBRT in metastatic insulinomas. [ABSTRACT FROM AUTHOR] more...

Hypoglycemia in critical care is a well-documented phenomenon, linking both physiological and clinical evidence to harmful outcomes and an increased risk of mortality. Its implications span medical and non-medical consequences, such as cardiovascular and cerebrovascular complications, and escalated health care expenses and hospitalization duration. Mitigation measures for modifiable risk factors and education for both patients and health care providers on hypoglycemia can effectively prevent the onset of inpatient hypoglycemia. This concise clinical review offers a brief overview of hypoglycemia in critically ill patients, encompassing its pathophysiology, etiology, diagnosis, management, and prevention. [ABSTRACT FROM AUTHOR] more...

Pancreatic neuroendocrine tumors (PanNETs) are generally hypervascular and readily detectable on imaging tests. However, hypovascular PanNETs are clinically problematic, requiring multiple imaging tests and tissue analyses to differentiate them from pancreatic ductal cancers. A 41 year-old man presented with Whipple's triad; 72 h fasting test followed by glucagon challenge test suggested insulinoma. However, contrast-enhanced computed tomography image showed a 17 mm tumor with poor enhancement and unclear borders in the tail of the pancreas. Abdominal magnetic resonance imaging and contrast-enhanced endoscopic ultrasonography (EUS) indicated cystic degeneration and necrosis at the same site; EUS-guided fine-needle aspiration cytology indicated a PanNET Grade 1 tumor. Although the imaging was inconclusive, diazoxide treatment ameliorated the hypoglycemia-related symptoms and insulinoma was deemed likely; following tail pancreatectomy and splenectomy, the symptoms disappeared. Pathological examination revealed a tumor positive for insulin and classed as PanNET Grade 1 according to the 2019 WHO classification. The microvessel density (MVD) of the tumor was found to be as low as 3.9%, which may partly account for the inconclusive images. The present case was difficult to diagnose preoperatively due to hypovascularity on imaging because of reduced MVD. It is clinically important to evaluate MVD in cases of hypovascular PanNETs by multiple preoperative imaging studies to differentiate them from pancreatic cancers and to validate the findings by postoperative pathological analysis. [ABSTRACT FROM AUTHOR] more...

Introduction and purpose Polyphagia is a rare symptom described as an excessive food intake due to an abnormally strong and persistent sensation of hunger or desire to eat. Diseases that can lead to polyphagia are numerous and include several medical specialties, such as endocrinology, neurology and psychiatry. Polyphagia leads to overweight and severe obesity, reduces quality of life, has a negative impact on the patient’s mental health and eventually causes premature death. Therefore identifying and addressing the root cause of polyphagia is crucial for effective management and treatment. This article aims to explore the most common causes, the latest research and potentials in the treatment of polyphagia. more...

ABSTRACT Insulinomas are the primary etiology of endogenous hyperinsulinemic hypoglycemia, which often manifest with Whipple’s triad and neuroglycopenic symptoms. Given the diverse clinical manifestation and subtle onset of insulinomas generally in a small size, detecting a minority of these generally small tumors can be challenging. We reported a case of a 44‐year‐old female patient with recurrent hypoglycemia accompanied by hyperinsulinemia, and the conventional imaging revealed no abnormality. With the aid of endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNAB), the insulinoma was precisely diagnosed and localized, and successfully excised via operation. The patient’s hyperinsulinemia and hypoglycemic episodes were relieved significantly after surgery. The application of EUS‐FNAB notably enhances the diagnostic accuracy for occult insulinomas, thereby informing appropriate surgical management. Herein, we advocate for invasive EUS examination in patients exhibiting strong clinical and laboratory indicators of insulinoma, even when conventional imaging results are negative. more...

Pancreatic neuroendocrine tumors (PNETs) are rare endocrine tumors originating from pancreatic cells, constituting 1-2% of pancreatic tumors. The incidence of PNETs has risen from 0.32 to 0.48 per 100,000 people between 2004 and 2021. Among PNETs, insulinomas are the most common type, characterized by excessive insulin production, with an occurrence rate of 1-4 per million people. This review provides a comprehensive analysis of insulinomas, focusing on their epidemiology, pathophysiology, clinical manifestations, diagnostic methods, and treatment strategies. Insulinomas can be sporadic or associated with Multiple Endocrine Neoplasia Type 1 (MEN-1) syndrome, a genetic disorder caused by mutations in the MEN1 gene. MEN-1-associated insulinomas are often diagnosed earlier and may present as multicentric lesions, whereas sporadic insulinomas are typically solitary and benign. Diagnostic approaches include biochemical tests, such as the 72-hour fasting test, and imaging techniques like CT, MRI, and nuclear medicine scans for tumor localization. Surgical resection remains the primary treatment modality, with high success rates for benign tumors, although emerging techniques like endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) offer promising alternatives for small, solitary tumors. Medical management, including medications like diazoxide and somatostatin analogs, is crucial for controlling symptoms in patients not amenable to surgery. Prognosis is generally favorable with surgical intervention, but careful monitoring is required for malignant or metastatic disease. Ongoing research is essential to enhance treatment strategies and improve patient outcomes. more...

Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156). more...

Insulinomas are rare functional neuroendocrine tumors that are usually indolent and small. Due to their rarity, there is often a delay in disease recognition and diagnosis, and small tumor size makes their localization challenging. Glucose monitoring and dietary modification with or without pharmacotherapy are crucial during diagnostics, and surgery is the only definite treatment. Continuous glucose monitoring (CGM) systems can be a valuable tool in managing insulinoma patients. We present three patients with confirmed endogenous hyperinsulinemic hypoglycemia undergoing tumor localization, medical treatment, and surgery while wearing a CGM system. By accurately depicting glucose fluctuations, CGM can help prevent hypoglycemia, decrease hypoglycemia unawareness, track hypoglycemia frequency, aid in medical therapy dose titration, and confirm a cure after surgery. more...

Introduction: Endogenous hyperinsulinaemic hypoglycaemia (EHH) is characterized by inappropriate insulin secretion from pancreatic beta cells despite low blood glucose concentrations. We aimed to evaluate the secular changes in presentation and management of EHH due to insulinoma/non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) at our centre. Methods: This was a single-centre ambispective study (2014–2022). The clinical, biochemical, hormonal and radiological parameters (n = 63) collected as part of this study were compared with our earlier studies (1992–2005, n = 31; and 2006–2013, n = 35) and with other centres across the world. Results: A total of 63 patients (39 males) with a preoperative diagnosis of EHH (insulinoma, n = 58; and NIPHS, n = 5) and a mean age of 40.7 years were studied. The mean lag time from the onset of symptoms to diagnosis decreased from 4.6 years during the first study period to 1.9 years during this study period. However, the majority presented with fasting hypoglycaemia of 98.4%, and both fasting and postprandial hypoglycaemia of 32%. Exclusive postprandial hypoglycaemia was present in 1.7% of insulinoma. A histopathological diagnosis of insulinoma was made in 52 patients and nesidioblastosis in two patients. Intraoperative ultrasonography (IOUS) and intraoperative palpation (IOP) yielded 100% sensitivity, while endoscopic ultrasonography (EUS) and 68Ga-DOTA-Exendin-4 positron emission tomography/computed tomography (PET/CT) yielded sensitivity of 86% and 85%, respectively, for localizing insulinoma. Resolution of hypoglycaemia was noted in 53 of 57 (93%) patients who underwent surgery with a preoperative diagnosis of insulinoma. Conclusion: We observed a trend towards earlier diagnosis of EHH, increased patient numbers and availability of nuclear imaging techniques for preoperative localization in the last decade compared to earlier. more...

When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors. more...

Introduction: Insulinoma is a rare disease, however the most common cause of hypoglycemia due to excess insulin secretion. Diagnosis and localization can be challenging. This study evaluated the clinical features, diagnostic workup, management, and outcomes of patients with insulinoma. Methods: The records of 13 patients with insulinoma who were followed up at İstanbul University, İstanbul Faculty of Medicine were retrospectively reviewed. Results: The mean age of the 13 patients (female/male: 11/2) was 43.9±12.5 years at diagnosis. The mean tumor diameter was 14.3±6.7 mm and localized at the head in 30.8%, at the tail and/or body in 61.6%, and at both the head and body in 7.6% of patients. The tumor was correctly localized by magnetic resonance imaging in 10/13 patients, 68Ga DOTATATE positron emission tomography/computed tomography in 4/8, endoscopic ultrasound in 3/7, and selective arterial calcium stimulation in 4/4 patients. Eleven patients were operated. Distal pancreatectomy was performed in 4 patients, distal pancreatectomy plus splenectomy in 3, and enucleation in 4 of the patients. The median follow-up duration was 4 years. In 8 patients, cure was achieved with surgery alone. Somatostatin receptor analog (SSRA) treatment was initiated in 2 cases and one of whom developed lymph node metastasis 2.5 years after surgery under SSRA treatment and she was reoperated. These patients had stable disease at the last visit. Conclusion: Insulinomas are usually small tumors, but they can cause severe symptoms. A multidisciplinary approach is required for diagnosis and treatment. In some patients, different imaging modalities may be necessary for tumor localization. more...

Background: Insulin-secreting tumors are the most common hormone-producing neoplasm of the gastrointestinal tract. Only 10 percent of overall cases of insulinoma have malignant variants, which have a poor prognosis. Cases Report: The present study reports an unusual case of pancreatic neuroendocrine tumor associated with hypoglycemia and liver metastasis as the initial presentation followed a rapidly progressive clinical course. A few cases of malignant insulinoma were reported with favorable responses in the literature. This research presents a patient with resistant malignant insulinoma who could not undergo an operation and received treatment with somatostatin analogs (S.S.A.), Peptide Receptor Radionuclide Therapy (PRRT), and other supportive care that was inappropriate. Conclusion: Early diagnosis and extensive treatment are auspicious for improving the prognosis of malignant insulinoma, and proper treatment with medications would increase the quality of life of patients. Nevertheless, unfortunately, late patient referrals, socioeconomic conditions, and being infected with Covid-19 disease resulted in death. more...

Insulinoma is the most common functional neuroendocrine tumor of the pancreas, with the main clinical symptom being hypoglycemia. The standard treatment is surgery, but some patients are not eligible for surgery, while in those operated on, the risk of perioperative complications is up to 30%. Diazoxide treatment to prevent hypoglycemia is effective only in 50% of patients. To prevent tumor growth and hormonal excess, stereotactic radiotherapy may be an alternative to surgical treatment. In our paper, we present two cases of patients with insulinoma treated successfully with stereotactic body radiation therapy (SBRT). more...

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients. more...

Insulinoma is one of the most common neuroendocrine tumors. As a result of endogenous organic hyperinsulinism, a hypoglycemic symptom complex develops, characterized by an attack of hunger, sweating, trembling, severe weakness and headache. To diagnose insulinoma and provide timely medical care during an attack of hypoglycemia, it is necessary to quickly and accurately measure blood glucose, not only in the laboratory, but also at home, which can be done using a glucometer. One of the most important aspects of measuring blood glucose, especially when severe hypoglycemia occurs, is the accuracy of the meter. Monitoring blood glucose during symptoms of hypoglycemia is possible with the help of an accurate, simple and convenient means of determining blood glucose, one of which is the Contour Plus One glucometer. Thanks to the improvement of technologies used in the Contour Plus One glucometer, the accuracy of blood glucose measurements increases, the procedure for glycemic control is simplified, which speeds up the provision of necessary medical care for hypoglycemia in patients with insulinoma. Accurate and rapid glucose control is necessary not only for diagnosing insulinoma, but also for self-monitoring of glycemia in patients with diabetes mellitus (DM). In addition to glycemic control, imaging studies that include computed tomography (CT), magnetic resonance imaging (MRI), transabdominal and endoscopic ultrasound, and molecular imaging methods are used to clarify the diagnosis of insulinoma. The radical treatment method is surgery, namely enucleation of the tumor or resection of part of the pancreas. In the vast majority of cases, surgery provides a complete cure. Conservative treatment tactics are considered when severe comorbidities and the patient's overall health status significantly exceed the risk of surgical intervention. The presented clinical observation demonstrates the classic clinical manifestations of insulinoma, the main laboratory and instrumental diagnostic methods: measuring blood glucose, including at home, using an accurate, simple and convenient glucometer Contour Plus One, fasting test, MRI, contrast-enhanced CT and immunohistochemical study. This clinical case of insulinoma is recommended for study by doctors of various specialties, primarily endocrinologists, oncologists and therapists. more...

Insulinoma is a rare neuroendocrine pancreatic tumor that typically produces excessive amout of hormone insulin. The main clinical manifestations of insulinoma are episodes of hypoglycemia. The low prevalence of the disease, the complexity of clinical and laboratory diagnosis, as well as the difficulty of topical diagnosis, low awareness physicians of related specialties, often cause untimely diagnosis of the disease, which worsens patients life-quality and prognosis. This article presents a clinical case of diagnosis and treatment of insulinoma in a non-specialized hospital. The article describes the methods of laboratory and topical diagnostics, as well as treatment tactics of patients with this disease. more...

Introduction: Insulinomas are the most frequent functional pancreatic neuroendocrine tumors. In about 10% of cases, insulinomas are associated with hereditary syndromes, including multiple endocrine neoplasia 1 (MEN1). Case Presentation: Herein, we present a 44-year-old female with recurrent hypoglycemia. In December 1998, this patient underwent resection of two pancreatic lesions due to hypoglycemia and was diagnosed with insulinoma. After the operation, the symptoms of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently, as did coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73 mmol/L and 15.2 U/L (2.6–11.8 U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of the somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT was added to localize the insulinoma. Most lesions with high expression of SSTR in the body and tail of the pancreas manifested parts of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide-1 receptor (GLP-1R) was only detected by 68Ga-exendin-4 PET/CT. It showed inter-tumor heterogeneity in the expression of SSTR and GLP-1R. From the distal pancreatectomy, a total of 5 tumors were found in the body and tail of the pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging findings of dual-tracer PET/CT. Conclusion: From this case, a combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients with MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contribute to detect all the NET lesions and locate the tumors with secretion of insulin. [ABSTRACT FROM AUTHOR] more...

Insulinomas are rare insulin-secreting tumors that most commonly affect adults. A 26-month-old child presented to her local emergency department with severe hypoglycemia. Initial workup was consistent with hyperinsulinemic hypoglycemia. Over the course of 10 months, multiple therapies for hyperinsulinism (HI) were trialed without significant benefit. Genetic testing for genes associated with HI was negative. At age 35 months, the patient was transferred to our center for further treatment. She underwent several imaging tests that revealed a lesion on her pancreas concerning for an insulinoma. The patient underwent surgical intervention to enucleate the lesion. Histopathological review of the specimen confirmed a benign, well-circumscribed insulinoma. A postoperative fasting test proved the patient was cured and she was discharged without the need for further glucose monitoring. [ABSTRACT FROM AUTHOR] more...