Using the Secretion Ratios of Insulin and C-peptide During the 2-h Oral Glucose Tolerance Test to Diagnose Insulinoma.

BACKGROUND: Insulinoma, owing to the low incidence and small volume of the tumor, is often undiagnosed. The 72-h fast test is centered on diagnosing insulinoma; however, it cannot be performed on outpatients. Our aim was to evaluate the results of a 3-h oral glucose tolerance test (3-h OGTT) for insulinoma diagnosis. METHODS: Thirty-seven patients with insulinoma were enrolled for comparison with 42 control subjects. All patients underwent 3-h OGTT with measurements of insulin and C-peptide. The secretion ratios of insulin and C-peptide at 1, 2, and 3 h were calculated by comparison with their values at 0 h. We used logistic regression analysis to establish the predictive models and compared the diagnostic efficiency by receiver operating characteristic analysis. RESULTS: The fasting insulin and C-peptide levels of insulinoma patients were both higher; however, the concentrations at 1 h and 2 h were both lower (P < 0.05). The levels at 3 h were not significantly different (P > 0.05). Our final logistic regression model was constructed as follows: logit (P) = 8.305 - 0.441 × insulin 2 h/0 h ratio - 1.679 × C-peptide 1 h/0 h ratio. A cutoff value of > 0.351 showed the highest diagnostic accuracy, with an area under the curve of 0.97, a sensitivity of 86.5%, and a specificity of 95.2%. CONCLUSIONS: The 2-h/0-h insulin ratio, as well as the 1-h/0-h C-peptide ratio, has high diagnostic efficiency for insulinoma. The 2-h OGTT can be an alternative test for diagnosing insulinoma in outpatient settings.

Factory-calibrated continuous glucose monitoring and capillary blood glucose monitoring in a case with insulinoma: usefulness and possible pitfall under chronic hyperinsulinemic hypoglycemia.

The accuracy of factory-calibrated continuous glucose monitoring (fCGM) within hypoglycemic ranges, especially under the status of chronic hyperinsulinemic hypoglycemia like insulinomas, remains an issue. Even so, fCGM is known to be useful for detecting hypoglycemia unawareness in insulinoma cases. A 25-year-old woman presenting with sudden unconsciousness was diagnosed with insulinoma; fCGM facilitated diagnosis by continuous monitoring for hypoglycemia. Before surgery, she was treated with continuous and frequent bolus infusions of 50% glucose via central venous catheter. To evaluate the accuracy of fCGM values in this case, a comparison between fCGM and capillary blood glucose (CBG) values was also performed. According to the simultaneously measured values, those of fCGM were largely in accordance with those of CBG. Moreover, compared with the previously reported case not having glucose infusions via central venous catheter, both the mean absolute relative differences (MARDs) and the absolute differences (Δ glucose) between fCGM and CBG values were larger in the present case, although no significant differences of MARDs and Δ glucose between the two cases were observed in several different conditions including fasting, post-meal, hypoglycemia, and others. Therefore, we should note possible increased differences between fCGM and CBG values in cases using frequent intravenous glucose infusions as well as case-dependent differing levels of consistency between them.

Usefulness of the index calculated as the product of levels of fasting plasma glucose and hemoglobin A1c for insulinoma screening.

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

New Diagnostic Criteria for the Localization of Insulinomas with the Selective Arterial Calcium Injection Test: Decision Tree Analysis.

PURPOSE: To explore optimal diagnostic criteria for localizing insulinomas with the selective arterial calcium injection (SACI) test using decision tree analysis. MATERIALS AND METHODS: A retrospective study included 86 vessels of 18 patients (5 men, 13 women; mean age 67 y; range, 49-73 y) with insulinomas who underwent SACI test between June 2007 and May 2016. Of 27 insulinomas, 7 were found in the head, 13 in the body, and 7 in the tail of the pancreas. Two patients had multiple tumors. To identify optimal diagnostic criteria, decision tree analysis was performed, and sensitivity, specificity, and accuracy of the conventional and the proposed new diagnostic criteria (plasma insulin concentration after calcium injection [ICpost] > 2.0 × plasma insulin concentration before calcium injection [ICpre]) were compared. RESULTS: The proposed new diagnostic criteria for insulinoma obtained by decision tree analysis were (i) ICpost > 2.7 × ICpre and maximum insulin concentration > 60.3 µIU/mL or (ii) ICpost > 2.7 × ICpre and maximum insulin concentration < 60.3 µIU/mL with ICpre being ≥ 7.5 µIU/mL. Sensitivity, specificity, and accuracy of the new criteria for the SACI test were 100%, 91.4%, and 94.2; sensitivity, specificity, and accuracy of conventional criteria were 100%, 69.0%, and 79.1%. CONCLUSIONS: New diagnostic criteria for localization of insulinomas with the SACI test yielded higher diagnostic performance than conventional criteria.

Clinical Management of Malignant Insulinoma: a single Institution's experience over three decades.

BACKGROUND: Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017. METHODS: "Malignant insulinoma" was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients' clinical information. We identified subjects diagnosed with malignant insulinoma based on clinical or surgical pathological signs and subsequently analyzed their clinical data. RESULTS: Eight males and seven females with a median age at diagnosis of 40 years (38-54 years) were included. Eight patients (53%) had developed metastases at diagnosis, while the others (46.67%) developed metastases during the follow-up visits. The major sites of metastasis were the liver (86.7%), local tissues and blood vessels (33%) and abdominal lymph nodes (13%). All patients displayed neuroglycopenic (100%) and/or autonomic (60%) symptoms, mostly during fasting periods (73.3%), with an average blood glucose level of 1.66 ± 0.51 mmol/L. A total of 93% of the patients had one primary pancreatic lesion, 53% had a lesion in the head of the pancreas, and 47% had a lesion in the tail of the pancreas, with diameters ranging between 0.9 and 6.0 cm. Most liver metastases were multiple lesions. Selective celiac arteriography yielded 100% sensitivity for both primary pancreatic lesions and liver metastases. Most patients received synthetical treatments, including surgery, chemoembolization, and octreotide. CONCLUSIONS: Malignant insulinomas have a similar diagnostic process to that of benign insulinomas but require far more comprehensive therapies to alleviate hypoglycemic symptoms and extend patients' survival.

Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test.

The 72-hour fast test is the current standard for the diagnosis of insulinoma. However, to conduct this test patients require hospitalization due to the chance of severe hypoglycemic episodes. Thus, it is costly and stressful for the patient. An out-patient test would serve the patient better and be more economical. Our aim was to evaluate the value of insulin to glucose and C-peptide to glucose ratios during a prolonged 5-hour oral glucose tolerance test (5-hour OGTT) in qualitative diagnosis of insulinoma, and to identify the optimal threshold for clinical screening. Initially, 15 subjects with pathological insulinoma and 12 control subjects with reactive hypoglycemia were enrolled in the study. A further 75 subjects with symptoms of hypoglycemia as a chief complaint at their initial clinic visit were subsequently screened. Serum insulin, C- peptide levels and blood glucose were quantified after a 5-hour OGTT in all participants and the ratios of serum concentrations of insulin and C-peptide to glucose were calculated. Subjects with insulinoma had significantly different insulin-to-glucose and C-peptide-to-glucose ratios from reactive hypoglycemia at the times of fasting, 4-hour post glucose load and 5-hour post glucose load. Higher specificity (73.08%) and sensitivity (82.67%) were achieved with the combined insulin-to-glucose ratio at the 5-hour post load and the C-peptide-to-glucose ratio at fasting. In combination, ratios of insulin and C-peptide release relative to blood glucose levels, measured during a 5-hour OGTT, may have important clinical value in the diagnosis of insulinoma.

Evolving management of insulinoma: Experience at a tertiary care centre.

BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia. METHODS: In this retrospective study, medical records of patients admitted with endogenous hyperinsulinemic hypoglycaemia were retrieved. Data pertaining to clinical features, diagnosis, imaging, surgery and patient outcome were extracted. The localization of insulinoma by preoperative imaging techniques was compared with the findings at surgery to assess the accuracy of localization. RESULTS: Fasting hypoglycaemia was present in all, and post-prandial hypoglycaemia (plasma glucose ≤50 mg/dl within four hours of meal) in 25.8 per cent. Mean duration of symptoms before reaching a diagnosis of hyperinsulinemic hypoglycaemia was 3.9 years. Mean duration of provocative fast was 21.8 h (range 6-48 h). Among the currently used imaging modalities, the sensitivity of localizing tumour was 79.3 per cent for multiphasic CT, 85 per cent for multiphasic MRI and 95 per cent for EUS. EUS detected tumour missed by both CT and MRI. All, except one of the operated patients, were cured by surgery. INTERPRETATION & CONCLUSIONS: Our results suggest that patients with insulinoma have a varied presentation. Multiphasic contrast-enhanced MRI/CT scan, EUS and ASVS may be complimentary in pre-operative localization.

Safety and tolerability of diazoxide in Japanese patients with hyperinsulinemic hypoglycemia.

Diazoxide is a non-diuretic benzothiadiazine derivative, one of a group of substances introduced into clinical practice in the 1950s for the treatment of hypertension. Fajans reported the use of diazoxide for the treatment of insulinoma in 1979. Although patients with hyperinsulinemic hypoglycemia worldwide have been treated with diazoxide for more than 30 years, there are no recent reports about the adverse effects of this drug in Asian patients, including Japanese patients. Herein, we report the results of our retrospective clinical record review of 6 Japanese patients (3 females and 3 males, ranging in age from 58 to 91 years) with hyperinsulinemic hypoglycemia and inoperable insulinoma treated with diazoxide. Diazoxide improved control of hypoglycemic symptoms and maintained normoglycemia in 5 of the 6 patients, and was ineffective in one patient. Surprisingly, although all 6 patients received diazoxide according to the treatment strategy recommended in Western patients, 5 of the 6 patients developed edema and two developed congestive heart failure. Thus, when starting treatment with diazoxide in Japanese patients, the symptoms and signs of fluid retention should be evaluated carefully. Also, appropriate protocols for treatment with diazoxide should be evaluated by means of clinical trials in Japanese patients with hyperinsulinemic hypoglycemia.

Recurrent Seizures Due to Pancreatic Insulinoma.

We present the case of a 70 year old man who was admitted with history of generalized tonic clonic seizures on and off since 6 years in spite of being on regular therapy with anticonvulsants. Patient was found to have hypoglycemia and was evaluated for same. He was diagnosed to have endogenous hyperinsulinemia due to pancreatic insulinoma. Patient underwent enucleation of tumor and was relieved of his symptoms.

Clinical presentation in insulinoma predicts histopathological tumour characteristics.

BACKGROUND: Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72-h fast. However, the prognostic value of parameters in the standardized 72-h fast on histopathological tumour criteria and clinical presentation has not been examined. METHODS: In thirty-three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki-67 index. Cut-off values for classical grading (G(clas)) were set at G1(clas) ≤ 2%, G2(clas) 3-20% & G3(clas) >20% and for modified grading (G(mod)) at G1(mod) <5%, G2(mod) 5-20% & G3(mod) >20%. RESULTS: When G(mod) criteria were applied, the initial blood glucose was lower in GII/III(mod) patients compared to GI(mod) (2.8 ± 0.8 vs 3.8 ± 1.3 mmol/l; P = 0.046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0.001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0.001) and c-peptide (basal c-peptide 5.4 ± 2.4 vs 2.7 ± 1.6 µg/l; P = 0.004; end of fast c-peptide 5.3 ± 2.4 vs 2.5 ± 1.4 µg/l; P = 0.001) were significantly higher in GII/III(mod) than in GI(mod). No differences between the groups were observed when G(clas) criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki-67 index and tumour size. CONCLUSION: This study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72-h fast. Lower initial blood glucose levels and higher concentrations of insulin and c-peptide are associated with worse tumour grading and larger tumour size.

Chronic hyperinsulinemia does not increase the production rate of high-density lipoprotein apolipoprotein AI: evidence from a kinetic study in patients with insulinoma.

OBJECTIVE: In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome. APPROACH AND RESULTS: We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× (P<0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× (P<0.05) higher in the fed state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3 ± 5.4 versus 59.6 ± 7.7 mg · kg(-1); P<0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30 ± 0.07 versus 0.20 ± 0.04 pool · d(-1); P<0.0001 and 14.6 ± 1.5 versus 11.5 ± 1.9 mg · kg(-1) · d(-1); P<0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3 ± 8.6 versus 49.3 ± 5.4 mg · kg(-1); P=0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20 ± 0.06 versus 0.30 ± 0.07 pool · d(-1); P<0.01 and 11.1 ± 1.6 versus 14.6 ± 1.5 mg·kg(-1) · d(-1); P<0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance. CONCLUSIONS: Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.

Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors. Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients. But peripheral blood levels of CgA are not routinely tested in Chinese patients with PNETs. This study was to assess the diagnostic value of CgA in Chinese patients with PNETs especially in patients with insulinomas. METHODS: Eighty-nine patients with PNETs including 57 insulinomas and 32 non-insulinoma PNETs as well as 86 healthy participants were enrolled in this study between September 2003 and June 2013. Serum levels of CgA were measured by ELISA method. Expression of CgA protein was detected in 26 PNET tissues including 14 insulinomas by immunohistochemical staining. RESULTS: Serum levels of CgA in 89 PNET patients were significantly higher than that in healthy controls (P = 7.2 × 10-9). Serum levels of CgA in 57 patients with insulinomas (median 64.8 ng/ml, range 25-164) were slightly higher than the levels in healthy controls (median 53.4 ng/ml, range 39-94) but much lower than the levels in 32 patients with non-insulinoma PNETs (median 193 ng/ml, range 27-9021), P = 0.001. The serum CgA levels were reduced in 16 of 17 patients with insulinomas after tumor resection. ROC curve showed that CgA values at 60 ng/ml distinguished patients with insulinomas from healthy controls but its sensitivity and specificity were 66.7% and 73.3%, respectively. In contrast, CgA values at 74 ng/ml distinguished patients with non-insulinoma PNETs from healthy controls, and the sensitivity and specificity were 65.6% and 91.9%, respectively. Except for two insulinomas with negative staining of CgA, 12 insulinoma tissues showed positive staining of CgA. CONCLUSION: CgA is a reliable serum diagnostic biomarker for PNETs but not for insulinomas.

Everolimus dramatically improves glycemic control in unresectable metastatic insulinoma: a case report.

Hypoglycemia poses a significant management challenge in patients with unresectable metastatic insulinoma. A 57-year-old woman with pancreatic neuroendocrine tumor with multiple liver metastases was referred to our institution. During the clinical course of pancreatic neuroendocrine tumor, she had experienced palpitations, cold sweats and faintness between meals that indicated her tumors had attained the characteristics of an insulinoma, and her quality of life was impacted by frequent hypoglycemic episodes which could not be prevented by conventional therapies. Shortly after the approval of everolimus for pancreatic neuroendocrine tumor in Japan, we began oral administration at 10 mg per day, which produced a rapid and substantial improvement in glycemic control. The serum insulin level decreased dramatically despite the tumor size remaining stable on computed tomography evaluation. Despite a dose reduction of everolimus to 5 mg per day in response to the adverse reaction of interstitial pneumonitis and a subsequent moderate increase in the serum insulin level, the patient has maintained normoglycemia for a year. Everolimus might represent the treatment of choice for unresectable insulinoma in terms of not only tumor stabilization but also glycemic control.

Sporadic insulinoma in a 10-year-old boy: a case report and literature review.

CONTEXT: Insulinoma is an exceedingly uncommon pancreatic islet cell neuroendocrine tumor. Its estimated incidence is approximately four cases per million individuals per year. CASE REPORT: We report the case of sporadic insulinoma in an exceptionally very young 10-year-old boy who presented with a 1-month history of episodic tremulousness, diaphoresis, increased hunger, confusion and fainting. Initial laboratory investigations showed low blood glucose (64 mg/dL) and high blood insulin (6 µU/mL) levels. Patient was admitted in view of frequent hypoglycemic symptoms and possible pancreatic insulinoma. A 48-hour mentored fasting test was done and ceased within 3 hours due to occurrence of hypoglycemic symptoms. During the episode, blood was drawn and results showed low blood glucose level and high insulin, pro-insulin and C-peptide levels. The hypoglycemic symptoms were relieved greatly by glucose administration and Whipple's triad for insulinoma was met. An abdominal contrast-enhanced computed tomography scan showed a 10 x 12 x 17 mm, small, well-demarcated, heterogeneously enhancing lesion within the body of pancreas without dilatation of pancreatic duct. No evidence of lymphadenopathy or distant metastasis was identified. Patient underwent enucleation of pancreatic tumor. Histopathological and immunohistochemical examination of the pancreatic mass confirmed neuroendocrine tumor (insulinoma). Patient had an uneventful recovery. A post-operative 6-month follow-up showed resolution of hypoglycemic symptoms, normalized blood glucose, insulin, pro-insulin and C-peptide levels, and no evidence of recurrence. CONCLUSION: Although rare, sporadic insulinoma should be considered in the differential diagnosis of any young individual presenting with frequent hypoglycemic symptoms (neuroglycopenic and/or autonomic nervous system symptoms). Furthermore, a literature review on insulinoma is presented.

A Systematic Review of the Accuracy of Insulin and C-peptide Secretion Ratios During the Oral Glucose Tolerance Test to Diagnose Insulinoma.

Background: Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma. Methodology: The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205). Results: A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9). Conclusion: The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.

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.

Presentation, diagnostic features and glucose handling in a monocentric series of insulinomas.

BACKGROUND: New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 µU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients. AIM: To evaluate clinical features, diagnostic criteria and glucose metabolic profile in a monocentric series of patients affected by insulinomas including two subgroups: sporadic and multiple endocrine neoplasia type-1 syndrome (MEN-1). SUBJECTS AND METHODS: Clinical, pathological and biochemical data regarding 33 patients were analyzed. RESULTS: following the current guidelines the 72-h fasting test was initially positive in all cases but one. In this case the test, initially negative, became positive after a 2-yr follow-up. Nadir insulin level was ≥ 3 µU/ml but <6 µU/ml in 3 patients and ≥ 6 µU/ml in the remaining 30 cases. At presentation, 27 patients (82%) reported only fasting symptoms, 3 (9%) only post-prandial and 3 (9%) both. Seven cases (21%) had previously been affected by type 2 DM or impaired glucose metabolism. CONCLUSIONS: In our series the new cut-off of insulin increased the sensitivity of the 72-h fasting test from 87% to 97%. The absence of hypoglycemia during the test cannot definitively rule out the diagnosis and the test should be repeated in every highly suspicious case. Post-prandial hypoglycemia can be the only presenting symptom. DM may be associated with the occurrence of insulinoma. So that a possible diagnosis of insulinoma must not be ignored if previous impaired glucose handling is evident.

Diagnostic accuracy of an "amended" insulin-glucose ratio for the biochemical diagnosis of insulinomas.

BACKGROUND: Recent biochemical diagnostic guidelines for insulinomas require demonstration of hypoglycemia with inappropriately elevated (nonsuppressed) insulin, C-peptide, or proinsulin, but these criteria may overlap with those in patients without insulinomas. Use of an "amended" insulin-glucose ratio that accounts for the normal variation in insulin secretion according to prevailing glycemia may improve diagnostic accuracy. OBJECTIVE: To compare the diagnostic accuracy of current diagnostic guideline criteria with the amended insulin-glucose ratio in patients with a suspected insulinoma. DESIGN: Retrospective cohort study. SETTING: 2 specialized university departments in Germany. PATIENTS: 114 patients with suspected hypoglycemia over 10 years having diagnostic prolonged fasts. MEASUREMENTS: Glucose, insulin, C-peptide, and the amended insulin-glucose ratio were measured during and at discontinuation of prolonged fasts. RESULTS: Of 114 patients who were evaluated, 49 had surgical resection of histologically confirmed insulinomas. Insulinoma was excluded in 65 patients; follow-up for a mean of 10 years (range, 0 to 16 years) showed no progressively severe hypoglycemic events or diagnoses of insulinoma. Patients with insulinoma had lower glucose levels and higher insulin and C-peptide levels overall than did control patients at the end of prolonged fasts, but there was considerable overlap. The amended insulin-glucose ratio correctly identified 48 of 49 patients with insulinoma and excluded the diagnosis in 64 of 65 control patients, resulting in positive and negative predictive values of 0.98 (95% CI, 0.89 to 1.00) and 0.99 (CI, 0.92 to 1.00), respectively, compared with 0.75 (CI, 0.63 to 0.85) and 0.98 (CI, 0.89 to 1.00), respectively, for glucose, insulin, and C-peptide concentration criteria. LIMITATION: The study had a retrospective design, no proinsulin concentrations were available, and a nonspecific insulin immunoassay (crossreactive with proinsulin) was used. CONCLUSION: The amended insulin-glucose ratio showed improved diagnostic accuracy over established criteria that use glucose, insulin, and C-peptide concentrations. PRIMARY FUNDING SOURCE: None.

[A case of glucose-sensitive insulinoma accompanied by slightly elevated serum insulin levels and persisting convulsions after the surgically removed neuroendocrine tumor]. / Glükózszenzitív insulinoma mérsékelten emelkedett széruminzulinszinttel, eltávolítása után is fennmaradó epilepsziás rohamokkal.

Insul(in)oma is a usually solitary or, in some cases, multifocal tumor of pancreatic beta cells. It may be a component of multiple endocrine neoplasia type 1. or von Hippel-Lindau syndrome. In typical forms the diagnosis - based on the Whipple triad - is simple, however, it may be difficult to recognize in cases with near normal or only slightly elevated serum insulin levels, as well as in patients with known convulsive episodes. With the case presentation of an 81-year-old woman the authors draw attention to the pitfalls of the correct diagnosis. A special feature of the presented case is that convulsions persisted after surgical removal of the pancreatic neuroendocrine tumor verified with functional and imaging methods. Recurrent or residual tumor was not found, and morphological damage of the brain was absent. In the background of the continuing convulsions cerebrovascular alterations as well as the cytotoxic effect of the hypoglycemia-induced excessive glutamate production can be postulated.