Insulinoma

Most common functional islet cell tumor of pancreas

Incidence: 1–4 per million population per year

Mean age of onset: 47 y

Presentation earlier (mean age 25 y) if part of MEN-1

More common in females

Hypoglycemia

Preop and intraoperative hypoglycemia

Post-excision rebound hyperglycemia (not always present and not reliable to validate completeness of resection)

Possibility of multiple islet cell tumors or MEN-1 characterized by primary hyperparathyroidism, anterior pituitary adenomas, and tumors of the pancreas and duodenum

80–90% are <2 cm, solitary, and benign.

Malignant lesions typically invade locally into surrounding structures or into the lymph nodes or liver

Insulinomas are found equally distributed throughout the pancreas (i.e., head, body, and tail).

5–10% occur in the setting of MEN-1; increased risk of recurrence if associated with MEN-1.

Presentation: Post-absorptive hypoglycemia, hypoglycemia after exercise, awakening at night to eat, and weight gain due to frequent meals to avoid hypoglycemic symptoms.

Differential Dx: Factitious hypoglycemia, liver or metabolic disease, NIPHS.

Dx strongly suggested by Whipple triad: (1) symptoms of hypoglycemia provoked by fasting; (2) blood glucose levels <50 mg/dL; and (3) relief of symptoms with glucose administration.

Typically blood glucose <45 mg/dL, insulin level >6 uU/mL, and C-peptide elevated to >200 pmol/L (with undetectable ketones/betahydroxybutyrate).

Gold standard for Dx: Measurement of plasma glucose, insulin, C-peptide, and pro-insulin during a 72-h fast with or without betahydroxybutyrate and absence of plasma levels of sulfonylurea. These tests in combination are sufficient to diagnose 97% of individuals.

Preop localization techniques include CT, MRI, PET, endoscopic US, octreotide scintigraphy, selective mesenteric angiography with intra-arterial calcium stimulation, and hepatic venous sampling for plasma insulin.

Preop imaging useful to evaluate for evidence of metastatic disease and to plan for the extent and type of surgery.

Preop localization fails 10–27% of the time.

Gold standard is firm biochemical Dx and selected preoperative imaging along with thorough pancreatic exploration and intraoperative US.

In absence of preoperative localization and intraoperative detection, blind pancreatic resection is not recommended.

Neurogenic symptoms are secondary to autonomic system discharge in response to hypoglycemia (anxiety, tremor, nausea, hunger, sweating and palpitations). Neuroglycopenic symptoms are secondary to CNS glucose deprivation (headache, lethargy, dizziness, diplopia, blurred vision, seizures, amnesia, confusion, and coma).