[Usefulness of arterial calcium stimulation with hepatic venous sampling in the localization diagnosis of endogenous hyperinsulinism]. / Valoración de la utilidad del test de estimulación intraarterial con calcio en el diagnóstico de localización del hiperinsulinismo endógeno.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization of tumors in patients with endogenous hyperinsulinism not detected with other methods. PATIENTS AND METHODS: We performed a retrospective study of 26 patients admitted to our hospital for hypoglycemia who underwent ASVS because the source of hyperinsulinism was not clearly identified by other imaging techniques. The histopathological result in patients who underwent a surgical procedure was considered the reference for statistical study of the accuracy of this technique. Statistical analysis was performed by comparing proportions with the chi-squared test with Yates' correction for contingency tables, and Cohen's kappa coefficient as a measure of interrater agreement between two observations. RESULTS: Surgery was performed in 17 patients, 13 with positive ASVS and the remaining four with negative results. An insulinoma was removed in 12 patients, and 10 of these were detected in the ASVS. A total of 76.9 % of positive ASVS tests corresponded to a histological diagnosis of insulinoma, and 83% of these insulinomas were positive in ASVS. This association was statistically significant (chi cuadrado=7.340; p=0.012). Two of three patients with nesidioblastosis had a positive response in the ASVS. A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (kappa=0.556, p = 0.007). CONCLUSIONS: ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism not detected by other imaging tests. This technique allows tumors in the pancreatic gland to be identified and may be useful in the choice of the surgical technique to be used.

Assessment of hyperinsulinaemia at the termination of the prolonged fast.

BACKGROUND: Traditional criteria to diagnose hyperinsulinaemic hypoglycaemia are based on insulin measurements by unspecific insulin assays. This study was performed to test whether these traditional criteria can be applied when insulin is measured by specific immunoassays. METHODS: 29 consecutive patients undergoing a prolonged fast were included; 11 patients with insulinoma and 18 healthy individuals. We determined plasma glucose, insulin, C-peptide, proinsulin, and beta-hydroxybutyrate concentrations at the termination of the fast. Insulin was measured by an unspecific radioimmunoassay (RIA) and a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: In 11 insulinoma patients, insulin concentrations at median plasma glucose concentration of 2.1 (range 1.3-2.5) mmol/l were 170 (76-340) pmol/l measured by RIA and 61 (11-156) pmol/l by ELISA. Insulin concentrations measured by RIA confirmed hyperinsulinaemia (i.e., >36 pmol/l, the proposed cut-off value for traditional insulin assays) in all insulinoma patients, whereas insulin concentrations measured by ELISA were <36 pmol/l in four patients. In three insulinoma patients, insulin concentrations measured by ELISA were <18 pmol/l, a proposed cut-off level to diagnose hyperinsulinaemia for specific insulin assays. CONCLUSION: When insulin concentrations are measured by specific immunoassays in patients evaluated for fasting hypoglycaemia, traditional reference values cannot be applied.

[Assessment of hypoglycemia]. / Abklärung von Hypoglykämien.

Hypoglycemia is characterized by a set of symptoms, but is not a diagnosis in itself. Initial attention should focus on documentation of the condition by typical symptoms (low blood sugar and disappearance of symptoms after glucose ingestion) before further testing is considered. To evaluate acute hypoglycemia, it is important to make an initial classification into one of three categories based on history: medication- or toxin-induced, fasting (not specifically associated with meals and usually occurring over 4 hours from the last meal) or postprandial hypoglycemia. A pathophysiologic approach to well-documented hypoglycemia leads to a straightforward strategy and to a diagnosis in most cases. True fasting hypoglycemia is almost invariably associated with a significant pathology, whereas postprandial hypoglycemia is not. An observed fast over 48-72 hours is diagnostic in nearly 100%. The diagnosis rests on several simultaneous features: hypoglycemia < 2.2 mmol/l, neuroglycopenic symptoms, and inappropriately elevated plasma insulin (> 30-40 pmol/l) and C-peptide levels (> 200 pmol/l) to document endogenous insulin release. Once the diagnosis of hyperinsulinism has been established, localization of the causative insulinoma (solitary adenomas in 80-90%) has traditionally been by means of the surgeon's fingers at laparotomy. In expert hands most tumors can be accurately located and removed. Although virtually every imaging technique has been advocated for preoperative localization of insulinomas, none has proved sufficiently reliable and surgical exploration is necessary even in the presence of a negative preoperative localization. Most patients who seek evaluation of reactive hypoglycemia describe a postprandial syndrome, which occurs with some regularity 2-4 hours after meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Relapse of medically treated insulinoma following the development of thyrotoxicosis: an assessment of potential mechanisms.

Increased thyroid hormone concentrations have been reported to have disparate effects on insulin sensitivity in man. We describe a 72-year-old lady who initially presented with episodic hypoglycemia secondary to an insulinoma that was controlled by diazoxide. She re-presented 12 months later with a recurrence of the hypoglycemia following the development of thyrotoxicosis. The diazoxide treatment was maintained and propranolol was introduced, which prevented further episodes of hypoglycemia. This appeared to be due to a direct effect of propranolol on endogenous insulin secretion, while whole body insulin sensitivity remained unchanged as assessed using the hyperinsulinemic-euglycemic clamp technique. She was later rendered biochemically euthyroid with a combination of blocking carbimazole therapy and thyroxine replacement, and this was associated with a marked decrease in insulin sensitivity. Thus, the principal effect of thyroid hormone excess in this patient was an increase in insulin sensitivity that led to the clinical relapse of the insulinoma.

A patient with insulinoma presenting for psychiatric assessment.

A case of insulinoma referred for psychiatric assessment illustrates the need for a high index of suspicion of organic mental disorder even in patients who have undergone previous extensive medical investigation. The diagnostic difficulties illustrate the need for persistence and cooperation between specialists in such cases.