A Case of a Metastatic Pancreatic Neuroendocrine Tumor: A Surgical Conundrum Wrapped in Functionality's Embrace.

This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

Outcomes of endoscopic ultrasound-guided ablation and minimally invasive surgery in the treatment of pancreatic insulinoma: a systematic review and meta-analysis.

Background and aims: Most pancreatic insulinomas can be treated by minimally invasive modalities. The aim of this meta-analysis was to assess the clinical outcomes of endoscopic ultrasound (EUS)-guided ablation and minimally invasive surgery (MIS) in the treatment of pancreatic insulinoma. Materials and methods: Online databases were searched for relevant studies. The primary aim was to compare the rates of adverse events (AEs) and the secondary aims were to compare the clinical and technical success rates, length of hospital stays, and symptom recurrence rates between EUS and MIS approaches. Results: Eight studies with 150 patients were identified that reported EUS-guided ablation outcomes, forming the EUS group, and 9 studies with 236 patients reported MIS outcomes, forming the MIS group. The pooled median age of the included patients in the EUS group was greater than that of the MIS group (64.06 vs. 44.98 years old, p < 0.001). Also, the technical success rate was significantly higher in the EUS group (100% vs. 96.6%, p = 0.025), while the clinical success was significantly higher (6%) in the MIS group (94% vs. 98.7%, p = 0.021). The AE rates (18.7% vs. 31.1%, p = 0.012) and severe AE rates (1.3% vs. 7.9%, p = 0.011) were significantly lower in the EUS group. The median length of hospital stay in the EUS group (2.68 days, 95% CI: 1.88-3.48, I2 = 60.3%) was significantly shorter than in the MIS group (7.40 days, 95% CI: 6.22-8.58, I2 = 42.2%, p < 0.001). The recurrence rate was significantly higher in the EUS group (15.3% vs. 1.3%, p < 0.001). Conclusions: EUS-guided ablation is associated with a lower AE rate and a shorter length of hospital stay, but a higher recurrence rate for the treatment of insulinoma compared with MIS. The EUS approach may be an alternative, even first-line, treatment for poor surgery candidates.

Induction of islet autoimmunity to defective ribosomal product of the insulin gene as neoantigen after anti-cancer immunotherapy leading to autoimmune diabetes.

Introduction: The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells. T1D patient-derived INS-DRiP specific T cells can kill beta cells and are present in the insulitic lesion. T cells reactive to INS-DRiP epitopes are part of the normal T cell repertoire and are believed to be kept in check by immune regulation without causing autoimmunity. Method: T cell autoreactivity was tested using a combinatorial HLA multimer technology measuring a range of epitopes of islet autoantigens and neoantigen INS-DRiP. INS-DRiP expression in human pancreas and insulinoma sections was tested by immunohistochemistry. Results: Here we report the induction of islet autoimmunity to INS-DRiP and diabetes after ICI treatment and successful tumor remission. Following ICI treatment, T cells of the cancer patient were primed against INS-DRiP among other diabetogenic antigens, while there was no sign of autoimmunity to this neoantigen before ICI treatment. Next, we demonstrated the expression of INS-DRiP as neoantigen in both pancreatic islets and insulinoma by staining with a monoclonal antibody to INS-DRiP. Discussion: These results bridge cancer and T1D as two sides of the same coin and point to neoantigen expression in normal islets and insulinoma that may serve as target of both islet autoimmunity and tumor-related autoimmunity.

Case report: Insulinoma masquerades as epilepsy - quantitative EEG analysis.

Insulinomas are rare gastrointestinal tumors with an incidence of 1-3 per million inhabitants annually. These tumors result in excessive insulin production, culminating in hypoglycemia. Such hypoglycemia triggers various central nervous system (CNS) manifestations, including headache, confusion, abnormal behavior, and epileptic seizures, which can lead to misdiagnosis as epilepsy. This case report documents a 46-year-old male who presented seizure-like episodes. Episodes occurred mainly during the night, lasting several minutes to hours. Initial seizures were characterized by bizarre behavior and altered responsiveness. Over time, seizure frequency, complexity, and severity escalated. We managed to record two episodes during long-term EEG and report, as the first ones, the detailed quantitative EEG analysis of these hypoglycemia-related events. EEG changes preceded the development of clear-cut pathological motor activity in tens of minutes and were present in all investigated frequency bands. The development of profound motor activity was associated with other increases in EEG power spectra in all frequencies except for delta. The most pronounced changes were found over the left temporal region, which can be the most susceptible to hypoglycemia. In our patient, the seizure-like episodes completely disappeared after the insulinoma removal, which demonstrates their relationship to hypoglycemia.

How should we differentiate hypoglycaemia in non-diabetic patients?

Hypoglycaemic syndromes are rare in apparently healthy individuals and their diagnosis can be a difficult challenge for clinicians as there are no shared guidelines that suggest how to approach patients with a suspect hypoglycaemic disorder. Since hypoglycaemia symptoms are common and nonspecific, it's necessary to document the Whipple Triad (signs and/or symptoms compatible with hypoglycaemia; relief of symptoms following glucose administration; low plasma glucose levels) before starting any procedure. Once the triad is documented, a meticulous anamnesis and laboratory tests (blood glucose, insulin, proinsulin, C-peptide, ß-hydroxybutyrate and anti-insulin antibodies) should be performed. Results can guide the physician towards further specific tests, concerning the suspected disease. In this review, we consider all current causes of hypoglycaemia, including rare diseases such as nesidioblastosis and Hirata's syndrome, describe appropriate tests for diagnosis and suggest strategies to differentiate hypoglycaemia aetiology.

Small Insulinoma Followed-up as an Indolent Pancreatic Tumor: A Case Report.

A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

A Rare Cause of Hypoglycemia in Elderly Patients: Insulinoma.

Insulinoma is the most common pancreatic neuroendocrine tumor and is often solitary and benign. To make a diagnosis, high insulin levels must be demonstrated, and proinsulin and C-peptide measurements must be done. The presence of hypoglycemic measurements and symptoms in the 72-hour fasting test is diagnostic. We present a case of a 91-year-old patient with no known diagnosis of diabetes mellitus who was admitted to the emergency department due to confusion. As a result of the clinical evaluation and differential diagnosis, it was determined that her complaint was due to hypoglycemia, and she was admitted to the internal medicine service for further examination, diagnosis, and treatment.

Spontaneous hypoglycemia: should we mind the gap? Long-term follow-up of healthy people who met Whipple's triad criteria.

CONTEXT: Patients discharged as "healthy" with the symptoms of spontaneous hypoglycemia, commonly known as Whipple's triad, need more attention. OBJECTIVE: Characterization and long-term follow-up of symptom development in patients with spontaneous hypoglycemia discharged as "healthy". The objective was to ascertain whether any conditions related to the symptoms were diagnosed during the follow-up period. METHODS: Retrospective analysis of patient data and evaluation of a specific questionnaire on the development of symptoms of spontaneous hypoglycemia. In addition, patient questionnaires were evaluated and primary care physicians were asked about possible diseases not recorded at baseline that occurred during the follow-up period. SETTING: Center for Endocrinology, Diabetology, and Osteology at the University Hospital Marburg, Inpatient Department, Germany. PATIENTS: All patients who presented to our center for the 72-hour fast between 2005 and 2018 and were discharged without an internal medicine diagnosis were included. INTERVENTIONS: Survey by questionnaire, via telephone interview. MAIN OUTCOME MEASURES: Patient-reported information on current symptoms compared to original symptoms, diagnosis of insulinoma or diabetes mellitus during follow-up, matched with primary care physician data, and metabolic and biometric data such as body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA IR), insulin sensitivity Matsuda Index (ISI-M), and area under the curve. RESULTS: A total of 41 datasets were evaluated at baseline and 38 patients were followed for an average of approximately 10 years. In total, 61% of respondents still reported the same symptoms as at baseline. No insulinoma was missed in these patients. Only two of the 38 patients developed diabetes mellitus. CONCLUSION: The high percentage of patients who are discharged as "healthy" and still have symptoms after many years is disturbing. It is possible that the symptoms are not due to low blood glucose. We urge caution with use of the term "healthy". We advocate a multidisciplinary therapeutic approach after an organic cause of hypoglycemia has been ruled out. Psychosomatic treatment seems to be useful. In addition, more research should be conducted on this topic.

Genetic disorders and insulinoma/glucagonoma.

Insulinoma and glucagonoma are two rare functioning neoplasms of the neuroendocrine cells of the pancreas, respectively, characterized by an uncontrolled over-secretion of insulin or glucagon, responsible for the development of the hypoglycemic syndrome and the glucagonoma syndrome. They prevalently arise as sporadic tumors; only about 10% of cases develop in the context of rare inherited tumor syndromes, such as multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC), being the result of an autosomal-dominant germline heterozygous loss-of-function mutation in a tumor-suppressor gene. Here, we reviewed the main epidemiological and clinical aspects of insulinoma and glucagonoma in the context of genetic syndromes.

Endoscopic loco-regional treatment in controlling pancreatic neuroendocrine tumors (PNETs) behavior: a case series and literature review.

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.

Short fasting test as a reliable and effective tool to diagnose insulinoma.

PURPOSE: The diagnosis of insulinoma can be challenging, requiring documentation of hypoglycaemia associated with non-suppressed insulin and C-peptide, often achieved during a prolonged 72 h fast performed in inpatient setting. Our goal is to predict weather a shorter outpatient fasting test initiated overnight and prolonged up until 24 h could be a sensitive method for diagnosing insulinoma. METHODS: We conducted a retrospective monocentric study on subjects admitted to our Unit of Endocrinology from 2019 to 2022 for clinical suspicion of insulinoma and underwent the short fasting test. A comparison between the short test group and the group of subjects who underwent the standard prolonged fasting test (from 2003 to 2018) has also been performed. The short fasting test was initiated by the patient overnight at home and proceeded the following day in outpatient setting (Day Hospital). As in the standard protocol, symptoms and capillary blood glucose (CBG) were strictly monitored. Venous blood was drawn for glycaemia, insulin and C-peptide at admission and at established intervals, in case of symptoms of hypoglycaemia or if CBG ≤ 45 mg/dl, when the fast would be suspended. RESULTS: The final sample consisted of 37 patients, with mean age of 44.5 ± 12.6 years (17-74). Short and standard tests were performed in 15 and 22 subjects, respectively. Diagnostic values for insulinoma were observed in 12 patients: in 5/15 who underwent the short fasting test, in 6/22 who underwent the prolonged test and in 1 patient who was initially negative on the short test and subsequently showed diagnostic values during the prolonged test. The diagnosis of insulinoma was achieved in 11/12 cases within 24 h of the beginning of the fast (91.7%). CONCLUSIONS: A short fasting test could be a valid, sensitive and reliable first-line workup in diagnosing insulinoma.

A rare case report of reversible glucose counterregulation in an insulinoma patient with type 2 diabetes.

CONTEXT: Insulinoma is a neuroendocrine tumor derived from pancreatic ß -cells whose clinical manifestation is recurrent hypoglycemia. Insulinoma in a patient with preexisting diabetes is extraordinarily rare, and the unmasking of type 2 diabetes (T2DM) after insulinoma surgery is even rarer. CASE REPORT: This article reports a 49-year-old male patient with insulinoma that masked the diagnosis of T2DM. The patient was admitted to the hospital with symptoms of hypoglycemia, such as repeated sweating, palpitations, and asthenia for over 4 years. The patient was diagnosed with insulinoma after completing relevant examinations. The emergence of hyperglycemia after the removal of insulinoma is attributable to the coexistence of T2DM. Surprisingly, a reversible decrease in cortisol levels was observed during the diagnostic process. We searched the previously published reports of this type of case from PubMed to determine why type 2 diabetes was covered by insulinoma and why glucocorticoids decreased. CONCLUSIONS: The diagnosis of T2DM in the patient after surgery may be related to increased food intake and insulin resistance induced by hyperinsulinemia caused by long-term hypoglycemia. The reversible decrease in cortisol levels, not adrenocortical insufficiency during the diagnostic process, may be caused by a transient abnormality in glucose counterregulation.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic insulinoma: a state of the art review.

INTRODUCTION: Insulinomas are the most common functional pancreatic neuroendocrine tumors (PNETs) that lead to incapacitating hypoglycemia. Guidelines recommend surgical resection as the mainstay of management. However, surgery is fraught with complications, causing significant peri/post-operative morbidity. Since insulinomas are usually benign, solitary, small (<2 cm), and do not need lymphadenectomy, hence, in this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is now being increasingly performed, to circumvent these adverse events and impairment of pancreatic function. AREAS COVERED: A comprehensive literature search was undertaken across various databases (PubMed/MEDLINE, Embase, Scopus), with no language restriction, for relevant articles (case series, reviews, case reports) pertaining to EUS-RFA for insulinoma and PNETs, till October 2023. In this review, we have explicated the role of EUS-RFA for insulinoma management, detailing thoroughly its mechanism of action, EUS-RFA devices with data on its safety and efficacy, and an algorithmic approach for its management. EXPERT OPINION: EUS-RFA is being advocated as a 'mini-invasive' option with the potential to replace surgery as a first-line approach for benign, sporadic, solitary, and small (<2 cm) insulinomas. Under real-time guidance, EUS-RFA has immense precision, is safe, predictable, with acceptable safety profile. Presently, it is being frequently performed for high-risk or inoperable candidates. Current need-of-the-hour is a randomized controlled trial to substantiate its role in the therapeutic algorithm for insulinoma management.

Artesunate Inhibits the Growth of Insulinoma Cells via SLC7A11/ GPX4-mediated Ferroptosis.

BACKGROUND: Artesunate (ART) has been recognized to induce ferroptosis in various tumor phenotypes, including neuroendocrine tumors. We aimed to investigate the effects of ART on insulinoma and the underlying mechanisms by focusing on the process of ferroptosis. METHODS: The CCK8 and colony formation assays were conducted to assess the effectiveness of ART. Lipid peroxidation, glutathione, and intracellular iron content were determined to validate the process of ferroptosis, while ferrostatin-1 (Fer-1) was employed as the inhibitor of ferroptosis. Subcutaneous tumor models were established and treated with ART. The ferroptosis-associated proteins were determined by western blot and immunohistochemistry assays. Pathological structures of the liver were examined by hematoxylin-eosin staining. RESULTS: ART suppressed the growth of insulinoma both in vitro and in vivo. Insulinoma cells treated by ART revealed signs of ferroptosis, including increased lipid peroxidation, diminished glutathione levels, and ascending intracellular iron. Notably, ART-treated insulinoma cells exhibited a decline in the expressions of catalytic component solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). These alterations were negated by Fer-1. Moreover, no hepatotoxicity was observed upon the therapeutic dose of ART. CONCLUSION: Artesunate might regulate ferroptosis of insulinoma cells through the SLC7A11/GPX4 pathway.

Insulinoma: Metastatic Recurrence 38 Years Following Initial Diagnosis in Pregnancy.

A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography. In 2022, a third operation was performed, with excision of a 4 × 3 mm tumor adjacent to the pancreatic head, and histology confirming insulinoma. She was again cured of symptoms.

Characterization and comparison of insulinoma tumor model and pancreatic damage caused by the tumor, and identification of possible markers.

Insulinoma is a neuroendocrine tumor. It arises from the uncontrolled proliferation of pancreatic ß cells. In this study, we created an insulinoma tumor model in nude mice. INS-1 cells were injected in two different ways, subcutaneously (S.C.) or intraperitoneally (I.P.). Body weight, tumor weight, and size were measured. ELISA kits were used analyze to Glucose, insulin, and CA19-9 levels in serum, pancreas, and tumor tissues. KCNN4, KCNK1, GLUT2, IR, HSP70, HSF1, and HSP90 levels were analyzed by western blotting of membrane and/or cytosolic fractions of tumor and pancreas tissue. Tumor formation occurred in nude mice, but it did not occur in Wistar albino rats. The tumor has neuroendocrine cell morphology. Insulin and CA19-9 levels increased in pancreas tissue. In tumor tissue, KCNN4 levels were higher in both membrane and cytosolic fractions, while KCNK1 levels were lower in the membrane fraction of the S.C. group. HSP70 levels were also lower in the S.C. group. In pancreas tissue, KCNK1 levels were lower in the membrane fraction of the S.C. and I.P. groups. GLUT2 levels increased in both groups according to the control group, while IR levels decreased in the S.C. group compared to the control group. However, HSF1 levels increased in the I.P. group, while HSP90 decreased in the S.C. group in pancreatic tissues. The S.C. group is a more suitable insulinoma tumor model. KCNN4, KCNK1, and HSP70 proteins may be important biomarkers in the diagnosis and treatment of insulinoma.

Effect of diazoxide on a cat with insulinoma.

Case summary: The patient was a castrated male American Shorthair cat, approximately 14 years old, weighing 3.4 kg. The patient had chronic kidney disease (CKD) (International Renal Interest Society stages 3-4) as an underlying disease. The cat was examined at a hospital for intermittent lethargy and seizures. Hypoglycaemia was repeatedly observed, and the insulin level was 1.78 ng/ml (reference interval 0.27-0.69) when the blood glucose was 49 mg/dl. Although the cat was tentatively diagnosed with insulinoma, surgery was not recommended because of the severe CKD. Although frequent feeding and prednisolone treatment were initially attempted, blood glucose decreased to 24-42 mg/dl. Diazoxide was additionally prescribed at a dose of 5.2 mg/kg q12h. The cat's clinical signs improved, and the blood glucose was in the range of 75-103 mg/dl during the first 2 months. It was maintained at >50 mg/dl until the patient died of renal failure 161 days after the start of diazoxide treatment. With regard to adverse events, vomiting once every 2-3 days without weight loss and non-regenerative anaemia were observed, which might have been at least partially caused by diazoxide treatment. An insulinoma was definitively diagnosed via pathological autopsy. Relevance and novel information: This is the first reported case of long-term treatment with diazoxide in a cat with insulinoma. Since it was effective in situations where conventional therapies were unsuccessful, diazoxide could be useful as a new therapeutic option for cats with insulinoma. Since adverse events, such as progression of vomiting frequency and non-regenerative anaemia, were observed, careful monitoring was required during administration.

Peptide Receptor Radionuclide Therapy Is Effective for Clinical Control of Symptomatic Metastatic Insulinoma: A Long-Term Retrospective Analysis.

Metastatic insulinoma is a rare malignant neuroendocrine tumor characterized by inappropriate insulin secretion, resulting in life-threatening hypoglycemia, which is often difficult to treat. There is currently very limited information about the efficacy of peptide receptor radionuclide therapy (PRRT) for clinical control of hypoglycemia. The aim of this long-term retrospective study was to evaluate the therapeutic efficacy of PRRT for improving hypoglycemia, to evaluate the change of medication after PRRT, and to calculate progression-free survival (PFS) and overall survival (OS). Methods: Inclusion criteria were histologically proven somatostatin receptor-positive metastatic malignant insulinoma and at least 2 cycles of [90Y]Y-DOTATOC or [177Lu]Lu-DOTATOC therapy from early 2000 to early 2022. A semiquantitative scoring system was used to quantify the severity and frequency of hypoglycemic episodes under background antihypoglycemic therapy (somatostatin analog, diazoxide, everolimus, corticosteroids): score 0, no hypoglycemic episodes; score 1, hypoglycemic events requiring additional conservative treatment with optimization of nutrition; score 2, severe hypoglycemia necessitating hospitalization and combined medication or history of hypoglycemic coma. Hypoglycemic score before and after PRRT was analyzed. Time of benefit was defined as a time range of fewer hypoglycemic episodes in the observation period than at baseline. Information on antihypoglycemic medication before and after therapy, PFS, and OS was recorded. Results: Twenty-six of 32 patients with a total of 106 [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC cycles were included. The average observation period was 21.5 mo (range, 2.3-107.4 mo). Before therapy, 81% (n = 21) of the patients had a hypoglycemia score of 2 and 19% (n = 5) had a score of 1. After PRRT, 81% of patients (n = 21) had a decreased score, and the remaining 5 patients showed a stable situation. There was temporary worsening of hypoglycemia just after injection of [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC in 19% of patients. The average time of benefit in the observation period was 17.2 mo (range, 0-70.2 mo). Antihypoglycemic medication reduction was achieved in 58% (n = 15) of patients. The median OS and PFS after the start of PRRT were 19.7 mo (95% CI, 6.5-32.9 mo) and 11.7 mo (95% CI, 4.9-18.5 mo), respectively. Conclusion: To our knowledge, our study included the largest cohort of patients with malignant insulinoma to be evaluated. Long-lasting symptom control and reduction of antihypoglycemic medications were shown in most patients after late-line PRRT.

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

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