Diagnostic and Management of Hyperinsulinism

Introduction to Hyperinsulinism

The simultaneous elevation of serum insulin and C-peptide suggests the presence of an insulinoma or other cause of endogenous hyperinsulinism, requiring thorough evaluation to exclude a pancreatic neuroendocrine tumor, as recommended by the National Comprehensive Cancer Network 1, 2

An insulinoma is a pancreatic neuroendocrine tumor characterized by inappropriate insulin secretion, accompanied by elevated C-peptide levels, with a diagnostic triad of Whipple including symptomatic hypoglycemia, low blood glucose (<55 mg/dL), and resolution of symptoms after glucose administration, as per the National Comprehensive Cancer Network guidelines 1, 3
Other causes of endogenous hyperinsulinism include insulin resistance/type 2 diabetes at an early stage, polycystic ovary syndrome, obesity, and the use of insulin-sensitizing medications like metformin, as noted in Diabetes Care 4, 5, 6

Confirmation of the association between hypoglycemia and hyperinsulinism involves a 48-72 hour fasting test under medical supervision, measuring blood glucose, insulin, and C-peptide levels simultaneously, and testing for sulfonylureas in the urine, as recommended by the National Comprehensive Cancer Network 1, 7
If endogenous hyperinsulinism is confirmed, pancreatic imaging such as CT or MRI scans should be performed, and consideration should be given to endoscopic ultrasound, which has a sensitivity of approximately 82% for localizing insulinomas, as per the National Comprehensive Cancer Network guidelines 1, 7, 8

Surgical treatment is recommended for localized insulinomas, which have an indolent course and can be cured surgically in 90% of cases, as noted in the National Comprehensive Cancer Network guidelines 1, 7
Preoperative stabilization of blood glucose levels through dietary measures and/or diazoxide may be necessary, with caution advised when using somatostatin analogs due to the potential for worsening hypoglycemia, as recommended by the National Comprehensive Cancer Network 1, 7

C-peptide is produced in equimolar quantities to insulin during the cleavage of proinsulin in pancreatic beta cells and is a better marker of endogenous insulin secretion due to its longer half-life and lack of hepatic extraction, as noted in Diabetes Care 4, 5
An isolated elevation of C-peptide without hypoglycemia is generally not pathological and may reflect insulin resistance, as per Diabetes Care guidelines 4, 5

A supervised 48–72 hour fast with simultaneous measurement of plasma glucose, insulin, C‑peptide, and proinsulin when glucose falls below 55 mg/dL is the standard approach to confirm endogenous hyperinsulinemic hypoglycemia. 9, 10

In patients with insulinoma, insulin and C‑peptide concentrations rise together during documented hypoglycemia, reflecting co‑secretion of the two peptides from the tumor. 9, 10