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.

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.

Functional assessment in the multimodality imaging of pancreatic neuro-endocrine tumours.

Pancreatic neuroendocrine tumours comprise a heterogeneous group that are rare but could result in serious manifestations. Surgical excision provides the best approach to treatment but many patients may have small lesions that are difficult to detect, or present with wide spread disease by the time of diagnosis. In addition to clinical assessment and biochemical tests, imaging is a major factor in establishing the diagnosis. Cross-sectional imaging such as US, CT and MR, play a major role in the initial assessment. However, they may miss small lesions or metastatic spread. Functional Imaging became possible with the development of somatostatin receptor imaging using 111In-octreotide, which when combined with anatomical imaging could provide enhanced detection. A major improvement has been achieved by combining receptor and PET inaging through the use of 68Ga-DOTA complexes that have been shown to have a much better sensitivity than other imaging modalities and can provide the basis for radionuclide treatment with 90Y or 177Lu labelled with DOTA complexes.

Assessment of suspected insulinoma by 48-hour fasting test: a retrospective monocentric study of 23 cases.

OBJECTIVE: Insulinoma causes fasting hypoglycaemia due to inappropriate insulin secretion. The diagnosis of insulinoma is based on Whipple's triad during a supervised fasting test. The aim of our study was to evaluate retrospectively the percentage of positive 48-hour fasting tests in a large series of patients with insulinoma. DESIGN, PATIENTS AND METHODS: In a retrospective study, we identified 39 patients (24 females, 15 men; average age 47 years [range 12-78 years]) with insulinoma. Sixteen patients were diagnosed by spontaneous hypoglycaemia. Twenty-three patients with insulinoma were tested with a 48-hour fasting test and compared to 31 healthy controls who had a negative fasting test and were followed up for at least two years. RESULTS: The fast was terminated due to neuroglycopenic symptoms in 4 patients (17.4%) at the 12th hour, in 17 patients (73.9%) at the 24th hour, and in 22 patients (95.7%) at the 48th hour. One patient with insulinoma had no neuroglycopenic symptoms, but was diagnosed by glucose and insulin levels during the 48-hour fast. Healthy controls had significantly higher blood glucose and lower insulin levels, and a lower insulin-glucose ratio than patients with insulinoma at the end of the fast. CONCLUSIONS: In conclusion, the 48-hour fasting test was successful in the diagnosis of insulinoma in 95.7% of patients. In this series we did not observe a need for fasting beyond 48 hours.

What preoperative assessment is necessary for insulinomas? Calculating the degree of waste: analysis of 29 cases.

In patients affected with insulinomas the preoperative work-up is debated. The success rate of various localisation procedures seems considerably inferior in respect to intraoperative results. Aim of the study is to evaluate our personal experience with this dichotomy. Twenty nine patients with definitive diagnoses of primary hyperinsulinemia from 1985 until June of 2001 were selected. Sensitivity, diagnostic accuracy, positive predictive value and cost of ultrasound (US) (29 pts.), computerised tomography (CT) (29 pts.), magnetic resonance imaging (MRI) (16 pts.), selective angiography (18 pts) and intraoperative ultrasound (IOUS) (18 pts.) in the localisation of neoplasm were evaluated. The presence of neoplasm was verified at operation or at autopsy in 27 cases (93%). The sensitivity of US, CT, MRI and selective angiography was 52%, 44%, 57% and 82%, respectively, with a cost of non-diagnostic studies equal to 422 [symbol: see text]/patient with a comprehensive waste equal to 43.7% of resources utilised. The sensitivity of IOUS and visualisation or physical exam by the surgeon was 100%, 46% and 96%, respectively. In 2 cases where there was a recurrence of symptoms after surgery, the histological exam of the operative specimen did not have evidence of insulinoma tissue. Surgery with the help of IOUS, preceded by only one pre-op diagnostic imaging technique represents the best approach for establishing the diagnosis of and treating insulinomas.

Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin-secreting tumours.

OBJECTIVE: Non-invasive localization modalities such as ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) often fail to localize insulinomas smaller than 2 cm in diameter. Recent studies have shown that the selective arterial stimulation and hepatic venous sampling (ASVS) technique using intra-arterial calcium as the insulin secretagogue facilitates the regionalization of such occult insulinomas. This study assesses the sensitivity of ASVS in localizing insulin-secreting tumours. SUBJECTS AND METHODS: Eleven consecutive patients (8 women), aged 29-82 years, were studied over the past 4 years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin-secreting tumour was proven in all patients. Calcium gluconate (0.025 mEq/kg body weight) was injected directly into the arteries supplying the pancreas and the liver. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60 and 120 s after each injection. The ASVS technique was performed in all 11 patients; the results were compared with the surgical findings in 10 patients and the autopsy findings in 1 case. The ASVS results were also compared with the findings of other, previously performed imaging modalities. RESULTS: ASVS correctly localized 4 insulin-secreting tumours to the head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1 to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological examination), sized 4-25 mm, were found in 10 patients. All were cured by selective surgery and remained free of hypoglycaemia over the next 1-4 years of follow-up. An insulin-secreting neuroendocrine tumour in the liver was documented in 1 case at autopsy. CONCLUSIONS: Arterial stimulation and hepatic venous sampling is a very sensitive technique for preoperative localization of insulin-producing tumours. It can help to plan minimally invasive surgery and to select an appropriate strategy for patients suffering from malignant tumours in others.

Value of intra-arterial calcium stimulated venous sampling for regionalization of pancreatic insulinomas.

BACKGROUND: Intra-arterial calcium stimulation with hepatic venous sampling (ASVS) for insulin gradients has been reported to be the most sensitive preoperative localizing technique for insulinomas. We reviewed our experience with ASVS to localize and guide the treatment of insulinomas over the past decade. METHODS: Eighteen patients who underwent ASVS before surgical exploration for insulinoma were studied. The accuracy of ASVS was compared with intraoperative findings and other localizing studies. RESULTS: There were no complications arising from the procedures. A more than 2-fold step-up in insulin level 30 to 60 seconds after injection to at least 1 feeding artery was observed in 16 patients. Fourteen of the 16 solitary tumors (87.5%) were correctly located; 100% (6/6 tumors) at the head and 80% (8/10 tumors) at the body/tail. The overall accuracy of this test was 89%, compared with 11%, 33%, 38%, and 63% of ultrasonography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, respectively. Six enucleations and 10 distal resections were performed, which included 2 laparoscopic procedures. The combination of intraoperative ultrasonography with preoperative ASVS identified all tumors. CONCLUSIONS: ASVS is the most accurate preoperative localization tool for the localization of insulinomas and, in combination with intraoperative ultrasonography, can enhance surgical success.

Assessment of immunoassays for insulin in diagnostic tests for insulinoma.

An immunoassay for insulin using a monoclonal insulin-specific antibody has been marketed in Japan for 2 years. This new assay may yield different plasma insulin (IRI) values from those obtained by the conventional immunoassay because of its high specificity. In this study, we compared IRI values obtained by three different immunoassays, assays P, M1 and M2, the last two of which involved monoclonal antibodies. For normal subjects, similar IRI values were obtained from all three assays. In patients with insulinoma, IRI values from assay M1 were 7-63% of those from assay P. Assays M1 and M2 gave similar values. Proinsulin interfered with assay P but not with assays M1 or M2. Differences between the IRI(P) value and the IRI(M1) or IRI(M2) value were correlated with the concentration of proinsulin (r = 0.98). The IRI(P) value appears therefore to represent the sum of levels of insulin and proinsulin. We conclude, therefore, that an immunoassay with broad specificity (i.e. assay P) is better for screening for hyper-(pro)insulinemia. Immunoassays with narrow specificity (i.e. assays M1 and M2) may have benefits in some tests aimed at tumor localization.

Preoperative endocrine tumor localization utilizing a cost-effective approach.

Endocrine tumors commonly produce characteristic clinical signs, and laboratory tests lead to accurate diagnosis in a high percentage of cases. The successful management of these tumors usually requires complete surgical resection. A large number of preoperative localization procedures to facilitate the operative management of these tumors have been developed. This report reviews the recent contributions to this literature, with a particular emphasis on cost-effective use of these procedures.

Surgical management of insulinoma: diagnosis of tumor location and high incidence of malignancy.

The findings in twenty-two patients with insulinoma were reviewed, as continuous efforts should be made to establish preoperative localization of the tumor. Superselective arteriography and percutaneous, transhepatic portal vein and pancreatic venous catheterization are highly recommended approaches. At the time of surgical intervention, a cautious exploration of the pancreas after thorough mobilization is most important. Recent use of intraoperative ultrasonography increases the likelihood of finding these occult tumors which locate deeply in the head of the pancreas. Apart from the diagnostic problems, we wish to emphasize the high incidence of malignancy (7/22, 31.8 per cent) in our series. Although patients with malignant insulinoma had a much better prognosis compared to those with a pancreatic ductal malignancy, pancreatic resection with regional lymphnode dissection seems to be a rational procedure. Enucleation can be done when intraoperative findings of the tumor and regional lymphnode indicate no malignant features and no multiple lesions. However, at the first operation, enucleation is still a procedure of choice, even for the malignant insulinoma in the head with a well-defined capsule and no metastatic lesions, the objective being to avoid a duodenopancreatectomy or total pancreatectomy.