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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]

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]

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]

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]

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]

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]

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]

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. [ABSTRACT FROM AUTHOR]

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]

Hyperinsulinism due to focal or diffuse pancreatic lesions causing recurrent episodes of hypoglycemia is rare in mid-childhood. There is no consensus on the gold-standard imaging method to diagnose focal insulin-producing lesions beyond infancy. A 14-year-old boy with a complex medical history and refractory epilepsy, presented with blood glucose (BG) of 52 mg/dL (2.9 mmol/L) (normal reference range: 70-100 mg/dL [3.9-5.6 mmol/L]) and increased seizure frequency. He failed a fast within 4 hours, with BG of 48 mg/dL (2.7 mmol/L) and insulin level of 4.6 µIU/mL (24.6 pmol/L) (diagnostic at the time of hypoglycemia >1.25 μU/mL [8.7 pmol/L]). Conventional imaging studies showed no pancreatic lesion. Fluorine-18-L-dihydroxyphenylalanine positron emission tomography/magnetic resonance imaging (18F-DOPA-PET/MRI) scan premedicated with carbidopa demonstrated intense focal 18F-DOPA uptake in the distal pancreatic tail. He underwent distal pancreatectomy. Histopathology showed focal pancreatic islet cell hyperplasia, with more than 90% of the neuroendocrine islet cells being positive for chromogranin and synaptophysin, with no loss of p57 staining. Genetic studies were negative for mutations in ABCC8 , KCNJ11 , GCK , or GLUD1 genes, multiple endocrine neoplasia (MEN) type 1, and Beckwith-Wiedemann syndrome. BG normalized after surgery. Seizure frequency improved. This case highlights the utility of 18F-DOPA PET/MRI imaging in diagnosing focal hyperinsulinism beyond infancy. [ABSTRACT FROM AUTHOR]

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]

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.

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

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.

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.

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.

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.

Introduction: Insulinomas are rare, usually sporadic, and typically benign pancreatic neuroendocrine tumours. Pre-operative localization is challenging and evidence on comparative analysis of anatomic and scintigraphic modalities for pre-operative tumour localization is limited, even in contemporary series. Methods: The current study was designed to study the clinical features and management challenges of insulinomas managed at a tertiary care centre. Clinical features, diagnosis, imaging techniques, surgical procedures, and outcomes details were collated. Pre-operative imaging techniques (CT/MRI, nuclear scintigraphy) were compared with intraoperative and histopathological findings to assess their accuracy of localization. Results: Thirty-seven patients (15 females [42%]; median age 36 years [IQR 28–49]) were included in the study. In four patients (10.8%), the tumour occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1) while the remaining were sporadic. The sensitivity of pre-operative localization was 61.5% (multiphasic CT), 66.6% (multiphasic MRI), 100% (68Ga Exendin-4 PET-CT), and 91.6% (EUS). Three patients with normal multiphasic CT had localization on 68Ga Exendin-4 PET-CT. The positive predictive value (PPV) of both Exendin-PET-CT and EUS was similar at 91.6% and 91.6%, respectively. All patients (except one with nesidioblastosis), who underwent enucleation or partial pancreatic resection, were cured. Conclusion: 68Ga Exendin-4 PET-CT based is a non-invasive imaging modality that has high sensitivity and PPV and can be used as a first-line imaging modality. The overall prognosis of these tumours is good with high cure rates attained following surgical resection.

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).

Insulinoma is the most common functional pancreatic neuroendocrine tumor, which is characterized by excessive endogenous insulin secretion and subsequent hypoglycemia. As a rare cause of hypoglycemia and syncope in the elderly, insulinoma is often ignored by clinicians. Compared with young and middleaged patients, elderly patients with insulinoma are more prone to fatal hypoglycemia and irreversible brain function damage. Early diagnosis and treatment can improve their quality of life and healthy life expectancy. On June 21,2021, a 73-year-old female patient with insulinoma was admitted to the hospital. By analyzing its clinical manifestations, qualitative and localization diagnosis, treatment and follow-up,it provided diagnosis and treatment ideas for the diagnosis, treatment and clinical management of insulinoma in the elderly. [ABSTRACT FROM AUTHOR]

Organelle heterogeneity and inter-organelle contacts within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here, we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capability by identifying distinct distribution patterns of insulin vesicles from INS-1E insulinoma cells. A multiple voltage DC-iDEP strategy with increased range and sensitivity has been applied, and a differentiation factor (ratio of electrokinetic to dielectrophoretic mobility) has been used to characterize features of insulin vesicle distribution patterns. We observed a significant difference in the distribution pattern of insulin vesicles isolated from glucose-stimulated cells relative to unstimulated cells, in accordance with maturation of vesicles upon glucose stimulation. We interpret the difference in distribution pattern to be indicative of highresolution separation of vesicle subpopulations. DC-iDEP provides a path for future characterization of subtle biochemical differences of organelle subpopulations within any biological system. [ABSTRACT FROM AUTHOR]

Introduction Neuroendocrine neoplasms (NENs) are heterogeneous group of neoplasms with relatively low incidence. Diagnosis of NENs requires an integrated approach of histology, immunohistochemistry, and molecular study. In the present study, we evaluated insulinoma-associated protein 1 (INSM1) expression in NENs and correlated it with other established neuroendocrine markers. Materials and Method Retrospective cross-sectional study was conducted in a tertiary care center. Consecutively, 100 cases from year November 2019 to January 2021 were enrolled in the study and all relevant data were noted. Results The mean (±standard deviation) age of the patients was 55.5 (±10.6) years with a male preponderance. Total 59% of the tumors were located in the lung of which 67% were poorly differentiated neuroendocrine carcinoma. INSM1 were positive in 97% cases, while synaptophysin (SYN) in 96% and chromogranin A (CgA) in 86%. Correlation of INSM1 expression with SYN and CgA was statistically significant (p -value < 0.05). Mean H-score of INSM1 was significantly higher than SYN and CgA and it was statistically significant (p -value < 0.001). Conclusion In the present study, the expression of INSM1 was seen in 97% cases of NENs. A statistically significant association was found between INSM1 and traditional NE markers. As a nuclear marker it is easy to interpret and it showed higher H-score. We conclude that INSM1 is a highly sensitive marker and recommend to incorporate it in the routine practice to aid in the diagnostic workup. However, a larger cohort is required to establish the organ-specific sensitivity and specificity of INSM1. [ABSTRACT FROM AUTHOR]

Non-somatostatin receptor expressing hypovascular insulinomas can be challenging to prove through imaging. This case highlights the utility of a structured approach to molecular imaging in patients with confirmed endogenous hyperinsulinemia. A 54-year-old woman was admitted because of a sudden loss of consciousness. Her relative reported that she complained of dizziness, intense sweating, blurry vision, and upper extremity tingling before becoming unresponsive for 20 min, after which the patient had little recollection of the event. She experienced similar episodes of shorter duration, trouble recalling everyday events, and unintentional weight gain of over 10 kg during the previous two years. Abdominal magnetic resonance imaging (MRI) and multidetector computerized tomography (MDCT) were unremarkable. Selective arterial calcium stimulation significantly increased hepatic venous insulin concentrations when the superior mesenteric and gastroduodenal arteries were stimulated. Technetium-99m (99mTc) octreotide single-photon emission computed tomography (SPECT) did not localize the lesion. Gallium-68 DOTA-Exendin-4 PET/CT acquisition was performed. A single intense 2 cm hyperperfused pancreatic lesion was located anteriorly in the head of the pancreas. Earlier targeted PET/CT imaging and recognition of significant neuropsychiatric symptoms attributable to the patient's hypoglycemic state might have accelerated the resolution of her condition and obviated the need for unnecessary testing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The radiosynthesis of pharmaceutical grade [68Ga]Ga-NODAGA-Lys40-Exendin-4 was accomplished in a fixed tubing-based module, EZ Modular-Lab Standard. Purification of the product via hydrophilic-lipophilic balance cartridge, yielded satisfactory results with radiochemical purity > 98%. The decay-corrected radiochemical yield (RCY) with 50 µg of Exendin-4[Lys40(NODAGA)] was (78.7 ± 0.8)%, which, by far, to the best of our knowledge, is the highest RCY reported till date, using an automated synthesizer. The quality control parameters were in accordance with that of gallium (68Ga) Edotreotide® Injections, featuring in the European Pharmacopoeia. Pre-clinical dosimetry studies in animal models, with co-administration of kidney protectant, demonstrates promising potential of the product towards clinical translation to insulinoma patients. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors (PNETs) are considered rare pancreatic neoplasms, and it is a challenging disease entity due to its indolent behavior and is difficult to manage. Diagnostic challenge is usually found in the imaging-based approach, such as transabdominal ultrasound, abdominal CT scan, and abdominal MRI. Surgery is still the main key player in controlling the disease. The main problems in clinical practice are the early detection of small PNETs lesion and non-functional PNET (NF-PNET) cases. Most cases usually come with large tumor size or metastatic disease. Endoscopic ultrasound (EUS) has been well-known as the most sensitive tool for early detection of pancreatic malignancy. It has now also been developed for managing pancreatic cancer, such as tumor ablation therapy. We presented four variety of PNETs cases (one patient with non-functioning PNETs and three patients with functioning PNETs) who have been successfully treated with EUS-guided radiofrequency ablation (RFA) with good control of tumor growth during follow-up. One patient with a large-size insulinoma could have the tumor controlled gradually after several EUS-RFA sessions. No adverse events or major complications were observed during and after the EUS-RFA procedure. EUS has been shown as a promising tool not only for more accurate diagnosis but also for tumor growth control. However, it would need further comparison studies between EUS and surgical approaches to make a better treatment strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state. Materials and Methods: We selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques. Results: Compared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F‐CPR <1.41 ng/mL and IA‐2A positivity, respectively. In contrast, the PPV of ELISA‐GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F‐CPR level, respectively. Conclusions: Our findings show that, unlike RIA‐GADA, ELISA‐GADA shows no association between GADA titers and the risk of progression to an insulin‐dependent state. The PPV improves when age at diagnosis, BMI and F‐CPR levels are considered in combination. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Insulinomas can present with neuroglycopenic symptoms suggesting neuropsychiatric disorders, delaying diagnosis and treatment. We recently treated a 65-year-old woman with insulinoma who was misdiagnosed at her nearby psychiatric clinic as having schizophrenia because of personality changes and memory impairment; she was treated with brexpiprazole, which was discontinued due to persistence of the symptoms. Despite her relatively low casual plasma glucose (70 mg/dL), the physician at the psychiatric clinic did not investigate the possibility of hypoglycemia, partly because her HbA1c level (5.2%) was within normal range. After skipping lunch one day, she was found by her family to be unable to communicate properly. She was transported to the emergency room of our hospital, where intermittently scanning continuous glucose monitoring (isCGM) use permitted detection of the hypoglycemia and led to a diagnosis of insulinoma and successful resection. A 72-h fasting test established hyperinsulinemic hypoglycemia. Contrast-enhanced computed-tomography and endoscopic ultrasonography together with selective arterial calcium stimulation test revealed an insulin-secreting tumor in the tail of the pancreas. Surgical resection of the tumor corrected her glucose and insulin levels as well as eliminated the insulinoma neuropsychiatric symptoms. Pathological examination showed that the tumor was positive for chromogranin A, synaptophysin and insulin. It is, therefore, important for physicians to be aware that insulinomas can manifest as neuroglycopenic symptoms and to consider the possibility of hypoglycemia by careful medical interview and isCGM, especially when patients suspected of psychiatric disorders do not show the expected response to antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Aims/Background: Insulinoma is an extremely rare condition in pediatric patients. This study aims to examine the pathological and clinical characteristics of pediatric insulinoma. Methods: A retrospective, single-center study was conducted involving five pediatric patients diagnosed with insulinoma. The study involved evaluating the postoperative status of the patients during follow-up and analyzing their clinical manifestations, diagnostic work-up, pathological findings, and therapeutic approaches. Results: The study cohort comprised four males and one female, aged between 4 and 9 years. Common symptoms included dizziness and fatigue. The insulinomas were located in various parts of the pancreas: two in the head, one in the neck, one in the body, and one in the tail. After undergoing subtotal pancreatectomy, four patients experienced no side effects during a follow-up period of 41 to 153 months. One patient, who underwent an incomplete pancreatic resection, required ongoing postoperative treatment with 150 mg Creon due to pancreatic enzyme deficiency. Postoperative pathological results indicated that all cases were low-grade neuroendocrine tumours, classified as grade 1 (G1) or grade 2 (G2). Two cases exhibited capsule invasion, and one case showed microvascular invasion. Despite these invasions, no recurrences or metastases have been observed to date. Conclusion: Surgical resection is a viable treatment option for pediatric insulinoma, yielding a favorable prognosis. The presence of capsular and microvascular invasions does not seem to affect the overall prognosis in these cases. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Hypoglycemia is a common complication following total gastrectomy, primarily caused by dumping syndrome and severe malnutrition, with late dumping syndrome being particularly significant. However, for recurrent fasting hypoglycemia, the possibility of insulinoma should be considered. Hypoglycemia caused by insulinoma can lead to severe consequences, including seizures and even death. Thus, it is crucial to differentially diagnose hypoglycemia occurring after total gastrectomy. Case Report: In this report, we present the case of a 36-year-old Chinese woman who underwent total gastrectomy for gastric cancer and subsequently received chemotherapy. Four months after surgery, she began experiencing recurrent seizures, and multiple tests confirmed hypoglycemia. A series of laboratory and imaging examinations ultimately led to a diagnosis of insulinoma. After surgical resection of the tumor, the patient's hypoglycemic symptoms resolved, and pathology results confirmed an insulinoma. Conclusions: This case report highlights the rapid weight loss and severe hypoglycemia observed in a patient only 4 months after total gastrectomy for gastric cancer. Although dumping syndrome was initially suspected based on the clinical course, the final diagnosis turned out to be insulinoma. The case underscores the importance of comprehensive evaluation and appropriate diagnostic investigations for patients experiencing hypoglycemia after total gastrectomy. Furthermore, the case suggests that the increased levels of enteroglucagon following changes in the gastrointestinal tract resulting from total gastrectomy may promote the development of insulinomas. This case report also contributes to the existing literature regarding atypical presentations of insulinomas and their association with gastric resection. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of β-cells in the pancreatic islets. T1D is preceded by islet-specific inflammation led by several immune cells. Among them, natural killer (NK) cells are emerging as important players in T1D development. Human NK cells are characterized by CD56 and CD16 expression, which allows classifying NK cells into four subsets: 1) CD56dimCD16+ or effector NK cells (NKeff); 2) CD56brightCD16- or regulatory NK cells (NKreg); 3) intermediate CD56brightCD16+ NK cells; and 4) CD56dimCD16- NK cells, whose function is not well determined. Since many studies have shown that T1D progression is associated with changes in various immune cell types, we hypothesize that the kinetics of NK cell subsets in the blood could correlate with different stages of T1D. To that aim, pediatric patients newly diagnosed with T1D were recruited, and peripheral NK cell subsets were analyzed by flow cytometry at several disease checkpoints: disease onset, partial remission (PR), 8 months (for non-remitters), and 12 months of progression. Our results showed that total NK cells and their four subsets are altered at the early stages of T1D. A decrease in the counts and percentage of total NK cells and NKeff cells at the different disease stages was found when compared to controls. These results suggest the extravasation of these cells into the islets at disease onset, which is maintained throughout the follow-up. By contrast, NKreg cells increased during the early stages after T1D onset, and both intermediate NK cells and CD56dimCD16- NK cells diminished at the PR stage, which might reflect the immunoregulatory attempts and could be candidate biomarkers for this stage. Also, CD56dimCD16- NK cells increased during T1D progression. Finally, changes in CD16 expression were identified in the different T1D stages, highlighting a CD16 expression reduction in total NK cells and NKeff cells 1 year after diagnosis. That may reflect a state of exhaustion after multiple cell-to-cell interactions. Altogether, our preliminary data provide a longitudinal picture of peripheral NK cell subpopulations during the different T1D stages, which could be potential candidate biomarkers indicators of disease progression. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia. We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events. The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50–2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05 – 0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30–5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60–2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60–3.95) mmol/L vs. 2.15 (IQR: 1.83 – 2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50–3.65) mmol/L vs. 2.20 (IQR: 1.80–2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose. The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011–2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates. [ABSTRACT FROM AUTHOR]

BackgroundInsulinomas 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.ObjectiveWe 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.MethodsWe 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.ResultsWith 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.ConclusionsSelective intraarterial calcium stimulation remains an important tool in localization of the source of insulin excess, especially in cases where other diagnostic modalities fail.

Background: The efficacy of insulin and C-peptide suppression (ICPS) test using a rapid-acting insulin analog to induce hypoglycemia in the diagnosis of insulinoma has never been studied. Objective: To compare the efficacy of using plasma C-peptide (PCP) and plasma insulin (PI) responses to the ICPS test using insulin aspart and the supervised prolonged fast (SPF) test in the diagnosis of insulinoma. Methods: The ICPS test was performed in 15 patients with insulinoma (IN) and 6 patients with non-insulinoma causes of hypoglycemia (non-IN) by intravenous infusion of insulin aspart to induce hypoglycemia. Plasma glucose (PG), C-peptide (PCP), and insulin (PI) levels were measured before and at the end of the test (end-ICPS) when the patients had hypoglycemia, defined by the presence of either PG ≤50 mg/dL with hypoglycemic symptoms or PG ≤40 mg/dL regardless of hypoglycemic symptoms. PCP and PI were measured by an immunoassay system that does not cross-react to insulin aspart (Cobas Modular Analytics e801). The SPF test was also performed in IN. Results: IN had a higher median end-ICPS PI (34.77 versus 0.58 μIU/mL, p

This article discusses a case study of a 59-year-old man who developed type B insulin resistance syndrome (TBIRS) after receiving anti-PD-1 therapy for Hodgkin lymphoma. The patient initially developed fulminant type 1 diabetes after starting treatment with sintilimab, and later presented with severe insulin resistance. TBIRS is a rare and challenging condition with a poor prognosis. This case highlights the need for further research and attention to immune-related adverse effects of anti-PD-1 therapy. The authors of the article conducted the study and provided the clinical diagnoses and treatments. No conflicts of interest were reported, and the research was conducted without any commercial or financial relationships. [Extracted from the article]