Insulinoma

Definition

Insulinoma is a rare neuroendocrine tumor of the pancreatic beta cells with autonomous, non-suppressible insulin secretion. The hallmark is fasting hypoglycemia; postprandial hypoglycemia occurs less often.

Occurrence & epidemiology

Insulinoma occurs in about 1 in 250,000 people; the median age at diagnosis is about 50 years. Around 10 % of insulinomas occur as part of multiple endocrine neoplasia type 1 (MEN 1); these patients usually develop the disease in their twenties, and the tumors are more often multiple.

Aetiopathogenesis

Insulinomas arise from islet cells. About 80 % are solitary, and only about 10 % are malignant. They are almost always located in the pancreas; in less than 1 % they are found ectopically in the duodenal wall or peripancreatic tissue. The tumor's insulin secretion is not suppressed by falling glucose; accordingly, beta-hydroxybutyrate is low during hypoglycemia.

Clinical features

Hypoglycemia typically occurs in the fasting state. Symptoms often develop insidiously and are easily mistaken for a psychiatric or neurological disorder.

• Neuroglycopenic symptoms: headache, confusion, visual disturbances, weakness, palsy, ataxia, marked personality changes, loss of consciousness, seizures, coma
• Sympathetic symptoms with a rapid fall in glucose: faintness, tremor, palpitations, sweating, hunger, nervousness
• The hyperinsulinism can contribute to weight gain.

Diagnosis

Biochemical confirmation

• Prolonged fast: because many patients are symptom-free at presentation, a supervised fast of 48–72 hours is performed. About 98 % develop symptoms within 48 hours, 70–80 % within 24 hours.
• Whipple's triad: symptoms during the fast, simultaneously documented hypoglycemia and relief after carbohydrate intake.
• Findings during hypoglycemia (glucose < 55 mg/dl or 3.0 mmol/l): inappropriate insulin secretion with a serum level of the hormone > 6 µU/ml (42 pmol/l), C-peptide ≥ 0.6 ng/ml (0.2 nmol/l), proinsulin ≥ 5 pmol/l, low beta-hydroxybutyrate and a rise in glucose after glucagon; screening for oral antidiabetic agents is negative.
• Distinction from factitious hypoglycemia: with surreptitious use of exogenous hormone, C-peptide and proinsulin are normal or low.

Localization

Localization studies follow only after biochemical confirmation. Endoscopic ultrasound has a sensitivity of more than 90 %; positron emission tomography (PET) can be added. CT has proven of little help in localizing these usually small tumors. Staging follows the TNM system for well-differentiated pancreatic neuroendocrine tumors.

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Further reading (open access)

1. MSD Manual Professional: Insulinoma
2. MSD Manual Professional: Hypoglycemia
3. MSD Manual Professional: Obesity

Cross-references