Mini-fasting tests diagnosing endogenous hyperinsulinism: a follow-up of 26 cases.

CONTEXT: The supervised 72-h fast remains the gold standard test for the diagnosis of endogenous hyperinsulinism and has recently been suggested to be shortened or even avoided. OBJECTIVE: This study aimed to evaluate whether measurement of blood glucose, insulin and C-peptide levels after a 12 h overnight fast (mini-fasting test), in at least 3 consecutive days, could allow making or ruling out diagnosis of endogenous hyperinsulinism, according to the Endocrine Society's recent guidelines. PATIENTS AND METHODS: We performed 12 h mini-fasting test in at least 3 consecutive days, dosing blood glucose, insulin and C-peptide levels in 26 inpatient patients with pathologically proven endogenous hyperinsulinism. RESULTS: In our series, 100% of patients showed insulin levels of at least 3 µU/ml and C-peptide levels of at least 0.6 ng/ml concomitant with symptomatic hypoglycemia (≤ 55 mg/dl). CONCLUSION: It leads to the conclusion that mini-fasting test might avoid, in most cases, prolonged fasting test for the diagnosis of hypoglycemia due to endogenous hyperinsulinism.

Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature.

OBJECTIVE: To report a case of a proinsulin-secreting islet cell adenoma in which the diagnosis was obscured by an ultraspecific insulin assay. METHODS: We describe the case of a 46-year-old woman, who presented with fasting hypoglycemia and appropriately low insulin values. RESULTS: A prolonged supervised fast produced symptomatic hypoglycemia (20 mg/dL) after only 7 hours. During the entire fasting test, highly specific insulin remained at <3 mIU/L, with a median value (and interquartile range) of 0.9 (0.8 to 2.3) mIU/L, when the glucose concentration was <50 mg/dL. The serum C-peptide level remained high normal (mean +/- SD, 2.7 +/- 0.6 ng/mL; normal fasting levels, 0.8 to 3.9), and no evidence of sulfonylurea use was detected in the patient's urine. Circulating proinsulin levels were persistently high (>200 pmol/L in all determinations when hypoglycemia was present; expected value, <5 pmol/L). Magnetic resonance imaging and endoscopic ultrasonography confirmed the presence of a 2.5-cm tumor in the head of the pancreas. A proinsulin-secreting islet cell tumor was diagnosed. Surgical resection of the tumor was successfully accomplished, but diabetes mellitus developed 4 months postoperatively. CONCLUSION: The diagnosis of a hypoglycemia-producing pancreatic adenoma can be missed when an ultraspecific insulin assay is used. The direct measurement of proinsulin established the diagnosis in this case.

Endogenous hyperinsulinemic hypoglycemia: diagnostic strategies, predictive features of malignancy and long-term survival.

Diagnostic strategies, malignancy predictors and long-term survival were retrospectively evaluated in patients with hyperinsulinemic hypoglycemia (64 insulinomas). Lower median glycemia was 30 (range 20-53) mg/dl [1.6 (1.1-2.9) mmol/l] with concurrent insulin of 48 (13.2-217) microU/ml and 15 (2-46) microU/ml measured by radioimmunoassay (RIA) and immunofluorimetric assay (IFMA), respectively. All patients with insulinomas had a positive prolonged fast within 48 h. Sensitivity of localization methods was: ultrasonography (US) 23%, computed tomography (CT) 28%, magnetic resonance imaging (MRI) 65%, endoscopic US 75%, arteriography 38%, portal venous sampling 67%, selective arterial calcium stimulation 67%, intraoperative US 94% and palpation 92%. Nine patients (14%) had malignant insulinomas. Age at diagnosis (mean+/-SD, 53.8+/-19 vs 39.4+/-16.3 yr; p=0.03), insulin (1372+/-730 vs 785+/-659% (percentage of the method's diagnostic cut-off; 6 and 3 microU/ml for RIA and IFMA, respectively; p=0.007) and C-peptide levels (9.8+/-2.9 vs 3.9+/-2.8 ng/ml (3.2+/-0.9 vs 1.3+/-0.9 nmol/l; p=0.006), and tumor size (6.2+/-4.1 vs 1.5+/-0.6 cm; p=0.0002) were increased in malignant insulinomas. C-peptide level above 6.1 ng/ml (2.0 nmol/l) had a 100% sensitivity and 96% specificity, and tumor size above 2.6 cm yielded a sensitivity of 88% and specificity of 100% in predicting malignancy. Survival of patients with malignant insulinomas was significantly impaired (16 vs 100% at 5 yr; p=0.0000001). The diagnosis of insulinoma can be made within 48 h of fasting. The association between intraoperative US and palpation evidenced the tumor in 95% of the patients. C-peptide and tumor size were reliable malignancy predictors.

[A new methodology for the preoperative localization of occult insulinomas]. / Nueva metodología para la localizacion preoperatoria de insulinomas ocultos.

UNLABELLED: In patients with hypoglycemic syndrome, preoperative localization of the insulinoma highly contributes to surgical removal. When the ultrasonography, computed tomography, magnetic resonance and pancreatic angiography fail to visualize the tumor, they are called occult insulinomas (OI). In this paper we describe the results of a new diagnostic method to localize OI, performed in 5 patients with hypoglycemic syndrome secondary to endogenous hyperinsulinism. In four out of five patients, computed tomography, magnetic resonance and angiography failed to show any tumor. In just one single case, these imaging methods showed the pancreatic tumor. All patients were studied by selective intraarterial pancreatic stimulation (SIPS): a) infusion of calcium gluconate (0.025 mEq/kg) in each artery that supplies the pancreas: gastroduodenal, superior mesenteric and splenic arteries as well as the hepatic artery; b) insulin venous sampling in the right supra-hepatic vein at 30 and 60 seconds after arterial stimulation (in one patient an additional sample at 90 seconds was obtained). The study was considered pathologic when the gradient (basal vs post-stimulus) increased at least 100%. RESULTS: In all five patients a pathological gradient was found. The suspected preoperative localization of the tumor was confirmed at surgery in four cases. The anatomopathologic examination revealed insulinoma in four cases and malignant insulinoma in the remaining. It is concluded that the results of this preliminary experience show the usefulness of SIPS in the preoperative localization of occult insulinomas.

Nueva metodologia para la localizacion preoperatoria de insulinomas ocultos / A new methodology for preoperative localization of occult insulinomas

En pacientes con síndrome hipoglucémico (SH) por hiperinsulinismo endógeno, la localización preoperatoria del Insulinoma facilita su exéresis. Debido a que los métodos diagnósticos, tales como ecografía, tomografía computada, resonancia magnética nuclear de abdomen y angiografía digital pancreática no suelen visualizar un tumor pancreático, han sido denominados insulinomas ocultos (IO). Describimos los resultados de un nuevo procedimiento diagnóstico para localizar IO, realizado en cinco pacientes con SH por hiperinsulinismo endógeno. En cuatro pacientes no se pudo, evidenciar tumor pancreático por tomografía resonancia y angiografía pancreática. Sólo en un paciente estos métodos demostraron tumor pancreático. Todos fueron sometidos a un test de estimulación arterial pancreática selectiva (TEAP): mediante a) inyección de gluconato de calcio (0,025 mEq/kg) en cada una de las arterias que irrigan el páncreas: Gastroduodenal, Mesentérica Superior y Esplénica y en arteria Hepática; b) obtención de muestras para insulinemia (IRI) de vena Suprahepática derecha a los 30 y 60 segs posteriores al estímulo (en un paciente se obtuvo además una muestra a los 90 Seg). Se consideró el resultado como patológico cuando el gradiente, entre las concentraciones basal y post-estímulo de IRI, en cualquiera de los tiempos considerados, se incrementaba mínimamente un 100 por ciento. Los cinco pacientes presentaron gradiente mayor al 100 por ciento. La localización presuntiva del tumor coincidió con la palpación y ecografía intraoperatoria en cuatro pacientes. El análisis histopatológico e inmunohistoquímico confirmó el diagnóstico de Insulinoma en cuatro pacientes y de insulinocarcinoma en el restante. Los resultados de esta experiencia preliminar evidencian la utilidad del TEAP para la localización preoperatoria de los IO.

Nueva metodologia para la localizacion preoperatoria de insulinomas ocultos / A new methodology for preoperative localization of occult insulinomas

En pacientes con síndrome hipoglucémico (SH) por hiperinsulinismo endógeno, la localización preoperatoria del Insulinoma facilita su exéresis. Debido a que los métodos diagnósticos, tales como ecografía, tomografía computada, resonancia magnética nuclear de abdomen y angiografía digital pancreática no suelen visualizar un tumor pancreático, han sido denominados insulinomas ocultos (IO). Describimos los resultados de un nuevo procedimiento diagnóstico para localizar IO, realizado en cinco pacientes con SH por hiperinsulinismo endógeno. En cuatro pacientes no se pudo, evidenciar tumor pancreático por tomografía resonancia y angiografía pancreática. Sólo en un paciente estos métodos demostraron tumor pancreático. Todos fueron sometidos a un test de estimulación arterial pancreática selectiva (TEAP): mediante a) inyección de gluconato de calcio (0,025 mEq/kg) en cada una de las arterias que irrigan el páncreas: Gastroduodenal, Mesentérica Superior y Esplénica y en arteria Hepática; b) obtención de muestras para insulinemia (IRI) de vena Suprahepática derecha a los 30 y 60 segs posteriores al estímulo (en un paciente se obtuvo además una muestra a los 90 Seg). Se consideró el resultado como patológico cuando el gradiente, entre las concentraciones basal y post-estímulo de IRI, en cualquiera de los tiempos considerados, se incrementaba mínimamente un 100 por ciento. Los cinco pacientes presentaron gradiente mayor al 100 por ciento. La localización presuntiva del tumor coincidió con la palpación y ecografía intraoperatoria en cuatro pacientes. El análisis histopatológico e inmunohistoquímico confirmó el diagnóstico de Insulinoma en cuatro pacientes y de insulinocarcinoma en el restante. Los resultados de esta experiencia preliminar evidencian la utilidad del TEAP para la localización preoperatoria de los IO. (AU)

Remission of symptoms of chemotherapy-refractory metastatic insulinoma using octreotide.

The symptoms resulting from the hyperinsulinemia of severe refractory metastatic insulinoma were palliated using self-administered divided doses of a long-acting minisomatostatin analog, octreotide. The substance was well tolerated and the attributable side effects were minimal (primarily gastrointestinal complaints). There were significant improvements in peripheral edema, ascites, and serum electrolytes throughout therapy. Serum insulin and glucagon levels were largely unchanged. Computed tomography scans performed during therapy showed stabilization of pancreatic and hepatic disease. Severe, recurrent hypoglycemic episodes due to hyperinsulinemia were reduced both in number and severity for almost a three-month period. This allowed the elimination or reduction of other chronic, supportive medications and improved quality of life.