Insulinoma: Incidence, cause, pathogenesis, symptoms, diagnosis, treatment, Complications


Insulinoma is an insulin-producing tumor of the pancreas that causes clinical scenarios such as Whipple’s triad ( i.e. symptoms of hypoglycemia after fasting or exercise, plasma glucose level less than 2.8 mmol/l and relief of symptoms on IV administration of glucose. Above 90% of them are benign and single, and can be cured by simple excision.



Insulinoma is the most frequent 70-80% among all functioning pancreatic endocrine tumors. 2-4 percent cases/million/year. It’s in all age groups diagnosed but mostly in 40-60 years of age people. Females are mostly affected.

Pathology and etiology

Uknown, no risk factors have been associated. Approximately 90% are solitary and nearly 10% are multiple and are associated with MEN 1 syndrome (multiple endocrine neoplasia type 1) and these patients frequently have multiple lesions and are at higher risk for malignancy.

Conditions that  are associated with insulinomas Pancreatic neuroendocrine tumors such as:

  • Gastrinoma 
  • Glucagonoma
  • VIPoma (vipoma is a non-beta pancreatic islet cell tumor which secrets vasoactive intestinal peptide (VIP)
  • Somatostatinoma
  • MEN 1 (multiple endocrine neoplasia type 1)
  • Von Hippel Lindau
  • Neurofibromatosis type 1

Sign and symptoms

Characterized clinically by hypoglycemic symptoms resulting from neuroglycopenia and catecholamine responses such as  (Diplopia, blurred vision, confusion, abnormal behavior, seizers, weakness, tremors, tachycardia, fatigue, nausea, palpation, hunger, etc .)


A fasting test that may last up to 72 hours is the most sensitive test. Mostly insulin, proinsulin, C-peptide, and blood glucose are measured in 1-2 hours interval to know inappropriate high secretion of insulin in relation to blood glucose. 

Approximately 80% of insulinoma diagnoses by fasting test and most of them in the first 24 hours time. Here elevated C-peptide demonstrates the endogenous secretion of insulin and that excludes factitious hypoglycemia that is caused by insulin injection.

6 criteria are used to diagnose an insulinoma such as:-

  • Documented blood glucose concentrations of 40 mg/dL or less.
  • Concomitant insulin concentrations of 6 μU/mL or greater.
  • C-peptide concentrations equal to 200 pmol/L or greater.
  • Proinsulin concentrations of 5 pmol/L or greater.
  • β-hydroxybutyrate concentrations of 2.7 mmol/L or less.
  • Absence of sulfonylurea (metabolites) in plasma and/or urine.

Diagnostic Imaging

Insulinoma can be localized by noninvasive means, using USG,  Computed tomography (CT) scanning, or Magnetic resonance imaging (MRI)  techniques. An indium-111 pentetreotide scan is more sensitive than USG, Computed tomography (CT), or Magnetic resonance imaging (MRI)  for the detection of somatostatin receptor-positive tumors, but not a good diagnostic tool for insulinomas.  An endoscopic USG has a sensitivity of 40-93% for detecting insulinomas.

Sometimes, angiography with percutaneous transhepatic pancreatic vein catheterization to sample the blood for insulin levels is required.

Differential diagnosis

  • Familial persistent hyperinsulinemic hypoglycemia of infancy (congenital hyperinsulinism)
  • primary islet-cell hyperplasia
  • noninsulinoma pancreatogenous hypoglycemia syndrome
  • post gastric bypass hypoglycemia (the latter two presenting primarily with postprandial hypoglycemia).

Medical treatment 

Diazoxide is the drug that suppresses insulin secretion by direct action on beta cells of the pancreas. 
If no surgical option to treat malignant insulinoma then chemotherapy applied and drugs include doxorubicin and streptozotocin.

Surgical treatment

Positive fasting test and exclusion of diffuse abdominal metastasis by USG or CT those all patients of insulinoma undergo surgical excision.
Depending on the location, insulinoma can be enucleated, might require partial or distal pancreatectomy or pancreaticoduodenectomy.

In the case of malignant insulinoma aggressive attempts at resection are done as these tumors are much less virulent than adenocarcinoma.
Insulinomas in MEN type 1 are at higher risk for being malignant and multifocal, requiring pancreatic resections.


Insulinoma complications may include:

  • Severe hypoglycemic reaction
  • Metastasis (The spread of a cancerous tumor to other part of the body)
  • Diabetes if the entire pancreas is removed but it is a rare complication, or food not being absorbed from intestine if too much of the pancreas is removed
  • Inflammation and swelling of the pancreas

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