This study is to evaluate the concept of the exenatide test for diagnosis of EHH (earlier induction of symptomatic hypoglycemia compared to placebo within 4 hours after injection).

Endogenous hyperinsulinemic hypoglycemia (EHH) is defined as inappropriate endogenous insulin secretion leading to hypoglycemia and associated symptoms. The most frequent diagnosis is an insulin-secreting pancreatic neuroendocrine tumor, but other diagnoses such as nesidioblastosis of the pancreatic islets are also possible. Biochemically, EHH is characterized by low glucose concentrations in the presence of inappropriately increased C-peptide (endogenous insulin secretion) and insulin levels. The conventional fasting test is at present the gold standard to document EHH.

Radiolabeled Exenatide for localizing insulinomas in patients with biochemically proven EHH has been evaluated and an exenatide-test in an outpatient setting may be able to replace the fasting test, by an early symptomatic hypoglycemia compared to a prolonged inpatient monitoring.

This study is to investigate the concept of the exenatide test to diagnose EHH.

Patients with suspicion for an insulinoma fulfilling all of the following inclusion criteria are eligible for the study:

Inclusion Criteria:

• Informed Consent as documented by signature
• Biochemically proven endogenous hyperinsulinemic hypoglycemia: neuroglycopenic symptoms in the fasting state with low plasma glucose, inappropriately high serum insulin and C-peptide concentrations (standardized 72h fasting test).).

Participants as control subjects fulfilling all of the following inclusion criteria are eligible for the study:

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Possession of the adequate match criteria (age, BMI and gender) to patients with suspicion for an insulinoma

Exclusion Criteria:

• Known hypersensitivity or allergy to Exenatide
• Pregnant or breastfeeding female patients. A pregnancy test will be performed in all women of child bearing potential.
• Calculated creatinine clearance below 40 ml/min
• No signed informed consent
• Intake of any glucagon-like peptide (GLP)-1 analogue (such as Byetta® or Bydureon®[= Exenatide])
• prediabetes or diabetes (HbA1c > 5.7 %)
• Previous abdominal surgery in the gastrointestinal tract
• Any concomitant glucose-lowering drug (i. e. insulin, sulfonyl urea)
• Any known intolerance to standardized meal (Maizena)
• Any uncontrolled significant medical, psychiatric or surgical condition (active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, uncontrolled congestive heart disease, etc.) or laboratory findings that might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study.
• Any mental conditions which prevent the patient from understanding the type, extent and possible consequences of the study and/or an uncooperative attitude from the patient