Insulinoma

Insulinoma is the most common functioning islet cell tumour, characterised by hypoglycaemia and often demonstrates hypervascular pancreatic lesions on imaging.

Description

Insulinoma is a neuroendocrine tumour originating from the beta cells of the islets of Langerhans in the pancreas. It is the most common functioning islet cell tumour and characterised by overproduction of insulin, leading to hypoglycaemia. They tend to manifest earlier and have a smaller size than other functioning and non-functioning endocrine tumours.

Pathogenesis

The pathogenesis of insulinomas is not entirely understood. However, they arise from the pancreatic beta cells that produce insulin. These tumours secrete insulin in an unregulated manner, independent of blood glucose levels, leading to episodes of hypoglycaemia.

Subtypes

There are no recognised subtypes of insulinoma.

Epidemiology, Risk Factors & Associations

• Most common functioning pancreatic neuroendocrine tumour (40-70% of cases)
• Peak incidence in the 5th decade of life, but can occur at any age
• No significant gender predominance
• Usually sporadic.
• Small proportion (<10%) is associated with Multiple Endocrine Neoplasia type 1 (MEN1)

Clinical Features

• Symptoms are often related to hypoglycaemia: confusion, sweating, tremor, palpitations, hunger, and in severe cases, seizures and loss of consciousness.
• Whipple’s triad is characteristic:
  1. Symptoms of hypoglycaemia
  2. Low plasma glucose at the time of symptoms
  3. Relief of symptoms after glucose administration.

Complications

• Metastatic disease is infrequent (<10%)
• Most common site of metastasis is the liver

Pathological Features

Histopathology

• Macroscopic: Usually small (<2 cm), solitary, well-circumscribed tumours
• Microscopic: Uniform cells with round-to-oval nuclei and minimal atypia. Characteristically demonstrate a trabecular, glandular or insular pattern

Serology

• High serum insulin and C-peptide levels during hypoglycaemia

Biochemistry

• Low plasma glucose (<2.8 mmol/L)

Radiological Features

General Features

• Characteristically demonstrate small, hypervascular pancreatic lesions¹

CT

• Non-contrast: Hypodense compared to the surrounding pancreas
• Contrast-enhanced: Intense homogenous enhancement during the pancreatic arterial phase (25-30 seconds post-contrast administration)

MRI

• T1WI: Hypointense relative to normal pancreas
• T2WI: Slightly hyperintense to isointense
• T1 C+: Intense homogenous enhancement during the early arterial phase
• DWI/ADC: May be hyperintense on DWI with low ADC values due to restricted diffusion

US

• B-mode: Hypoechoic, well-circumscribed lesion
• Colour Doppler: Increased vascularity

NM

• PET FDG: Insulinomas are often not FDG-avid
• Ga-68 DOTATE: Shows focal intense tracer uptake

Grading and Staging

WHO classification of pancreatic neuroendocrine tumours is typically used. Insulinomas are usually low-grade (G1).

Diagnosis

Diagnosis is confirmed by demonstration of inappropriately high serum insulin and C-peptide during a hypoglycaemic episode, in combination with imaging findings.

Differential Diagnosis

• Pancreatic neuroendocrine tumours (non-functional): Can have similar imaging features but do not cause hypoglycaemia.
• Pancreatic adenocarcinoma: Typically demonstrates hypovascular mass. Patients often present with jaundice, weight loss, and abdominal pain.
• Pancreatitis: Characteristically demonstrates pancreatic inflammation with or without associated fluid collections. Can also cause pancreatic mass effect but does not cause hypoglycaemia.

Management

• Surgical resection is the treatment of choice.
• For unresectable or metastatic disease, medical management with diazoxide or somatostatin analogues may be used.

References

1. Lewis, R.B., Lattin Jr, Maj, G.E. and Paal, E., 2010. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics, 30(6), pp.1445-1464. ↩︎