Insulinoma

Insulinomas are predominantly benign, pancreatic islet beta-cell tumors associated with increased insulin production. While most insulinomas are sporadic, some are associated with multiple endocrine neoplasias (e.g., parathyroid tumors, pituitary adenomas, gastrinomas). Insulinomas present clinically with recurrent attacks of hypoglycemic symptoms that subside after glucose intake. The diagnosis is established by demonstrating inappropriately elevated serum insulin following a fasting test. Insulinomas are differentiated from other causes of hyperinsulinemia (e.g., exogenous insulin administration) by the presence of elevated levels of proinsulin and C-peptide. The treatment of choice is surgical enucleation of the insulinoma. In inoperable cases and patients with persistent hypoglycemic attacks, diazoxide can be used to decrease insulin secretion.

• Sex: ♀ > ♂
• Age range: ∼30–60 years
• Incidence: ∼ 4 cases/1,000,000 persons per year ^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Insulinomas are neuroendocrine tumors that arise from beta cells of the pancreas ^[1]
  • < 1% occur at ectopic sites (e.g., spleen).
  • ∼ 90% of insulinomas occur as solitary tumors ^[1][2]
• Most insulinomas occur sporadically
• Over 90% of insulinomas are benign ^[1]
• ∼ 5% of insulinomas are associated with multiple endocrine neoplasia type 1 (MEN 1). ^[3]

References:^[4][5]

• Clinical features of hypoglycemia, including lethargy, syncope, and double vision
  • Relief of symptoms after administering glucose (See also Whipple's triad.)
• Weight gain
• Symptoms characteristic of other endocrine neoplasias may occur (see article on multiple endocrine neoplasias for more information).

References:^[4][5]

• Hypoglycemia with inappropriately high insulin levels (hyperinsulinism)
• Fasting test: Positive if serum glucose levels remain low (< 40 mg/dL) and insulin levels remain high even after fasting for 72 hours.
• ↑ C-peptide and ↑ proinsulin levels
  • Elevated C-peptide levels are not seen with the use of exogenous insulin (e.g., factitious hypoglycemia)
• Imaging (endoscopic ultrasonography, CT, MRI, selective angiography): for surgical planning

Elevated C-peptide and proinsulin levels may also be the result of sulfonylurea use! This can be ruled out by screening serum samples for sulfonylureas.

References:^[4][6][7]

• Surgery
  • Treatment of choice if tumor is operable
  • Surgical enucleation of the pancreatic adenoma (by either open surgery or laparoscopy)
• Medication
  • Treatment of inoperable tumors or recurrent hypoglycemic attacks despite surgery
  • Inhibitors of insulin release
    • Diazoxide ^[7]
    • Octreotide

References:^[3][7][8]