Rare, usually benign, neuroendocrine tumours of the pancreas that can occur sporadically or as a part of the MEN-1 syndrome.

• M/C cause of hypoglycemia-related to endogenous hyperinsulinism
• M/C functioning endocrine neoplasm, M/C neuroendocrine tumour of the pancreas

Salient features:

Rule of 10s:

• 10% malignant
• 10% ectopic
• 10% MEN syndrome
• Nesidioblastosis rare in adults, more common now with gastric bypass (NIHPPS)

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Aetiology

Sporadic insulinoma (90% cases)

Multiple endocrine neoplasia type 1 (MEN-1) associated insulinoma:

Autosomal dominant inheritance due to inactivating mutations of the MEN1 gene located on chromosome 11.

• Primary hyperparathyroidism
• Anterior pituitary adenomas
• Tumours of the endocrine pancreas & duodenum
  • M/C functioning islet cell tumours in MEN-1: Gastrinomas and insulinomas (10% MEN-1 cases)

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Pathophysiology

• Sporadic insulinomas:
  • Typically <2 cm size (90% cases), solitary (90% cases) and benign (90% cases)
• MEN-1 associated insulinomas:
  • Develop earlier and tend to be multifocal, occurring throughout the pancreas

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Clinical presentation

Whipple’s triad (diagnostic hallmark):

• Hypoglycemia symptoms (provoked by fasting)
• Glucose < 50mg/dl (at time of presentation)
• Relief of symptoms on glucose administration

Hypoglycemia activates the adrenergic and cholinergic nervous systems and depending on the degree of the hypoglycemia presents different levels of impairment of neurologic function:

Neurogenic	Neuroglycopenic
Adrenergic: Palpitations Tremor Anxiety/arousal/nervousness Cholinergic: Sweating/diaphoresis Hunger Paresthesiae Circumpolar tingling	Blurred Vision Cognitive impairments Behavioral changes Psychomotor abnormalities Confusion Disorientation Memory Loss Seizure Stupor

Case study:

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Diagnosis

Lab studies:

• Blood glucose <50 mg/dl with hypoglycemic symptoms
• 72-h monitored fast (GOLD STANDARD)
• Relief of symptoms after eating
• ↑ plasma insulin (≥6 μU/ml)
• ↑ C peptide (≥0.2 nmol/l): Can differentiate from excessive exogenous insulin administration
• ↑ proinsulin (≥5 pmol/l)
• Absence of  sulfonylurea (metabolites) in plasma/urine

Noninvasive localization studies:

• Trans-abdominal ultrasonography, computed tomography (CT) and MRI.

Invasive localization studies:

• Intra-arterial calcium stimulation with hepatic vein catheterization
  • Older studies:
    • Pancreatic angiography
    • Transhepatic portal venous sampling (THPVS)
• Endoscopic ultrasound (EUS)
• Intraoperative ultrasonography (IOUS): Best investigation for localization

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CT-scan:

MRI:

Endoscopic ultrasound (EUS):

Angiography and arterial stimulation venous sampling:

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Management