Presenting Complaint

The presenting complaint for GEP-NETs varies widely.

  • Patients with pancreatic NETs often present with symptoms related to the functional hormone that is produced; although around 30-40% of tumours may be non functional:
    • Patients with insulinoma present with paroxysmal hypoglycaemia
    • Patients with gastrinoma present with severe abdominal pain due to extensive gastric ulceration
    • Patients with VIPoma present with profuse watery diarrhoea
    • Patients with glucagonoma present with weight loss and migratory necrolytic erythema
    • Patients with somatostatinoma present with vague abdominal pains and diarrhoea
    • Patients with non-functioning pancreatic NETs present with symptoms of mass effect such as early satiety and abdominal fullness. These tumours are often much larger due to later presentation
  • Patients with upper gastrointestinal NETs usually present with obstructive symptoms or gastric ulceration. Most tumours are non functional
  • Patients with small bowel NET often develop carcinoid syndrome, usually only seen when liver metastases have developed.
  • Patients with neuroendocrine tumours of the appendix are often found incidentally during appendectomy (1/300 cases) but may also develop carcinoid syndrome in advanced cases
  • Patients with NETs of the distal bowel are often asymptomatic and patients are found incidentally or during colonoscopy for other reasons

Any patient with gastrointestinal neuroendocrine tumour and liver metastases may develop symptoms and signs of liver failure such as jaundice, fatigue and clotting disorders. NETs arising from the midgut have the highest propensity for causing carcinoid syndrome.

Carcinoid Syndrome

Carcinoid syndrome develops in the setting of metastatic neuroendocrine tumours of the small bowel, proximal large bowel or appendix. It is rare with neuroendocrine tumours at other gastrointestinal sites but is also seen in well differentiated bronchial neuroendocrine tumours without liver metastases. The classical symptoms are:

  • Flushing, which may occur spontaneously or in response to other activities. It may also occur extensively with anaesthesia, leading to profound hypotension which can be fatal (~ 90% of patients)
  • Profuse secretory diarrhoea (> 10 watery motions/day) (>80% of patients)
  • Valvular heart disease
  • Bronchospasm (uncommon)


Examination may be unremarkable. Some patients develop cutaneous vascular lesions in end stage disease. Patient with liver metastases may have hepatomegaly, jaundice or ascites.

Pathology Tests

Patients with hormone producing tumours (most pancreatic NETs and small bowel NETs) may have measurable levels of hormones in the blood. In addition, small bowel NETs (which generally produce serotonin) may be detectable through urinary 5-hydroxyindoleacetic acid (5-HIAA), the final breakdown product of serotonin.


Cross Sectional Imaging

CT provides good imaging resolution of most NETs as well as liver metastases. Liver metastases have a similar appearance to hepatocellular carcinoma (ie. early contrast uptake and washout compared to the liver parenchyma). MRI has improved accuracy in the detection of liver metastases.

Nuclear Medicine Imaging

Somatostatin receptors are often expressed by neuroendocrine tumours and functional imaging is possible through the use of somatostain analogues (usually octreotide).

  • Somatostatin Receptor Scintigraphy (using radiolabeled octreotide) is similar to whole body bone scan and images are acquired through a gamma camera. Modern scintigraphy techniques (eg. SPECT) allow 3D localisation of areas of uptake. SRS is useful for detection of primary disease and metastatic sites, although modern cross sectional imaging also capable of doing this. Scintigraphy techniques are limited by the general poor resolution of nuclear medicine techniques (poor detection of tumours < 1 cm)

PET Scanning using specialised molecules that are taken up by neuroendocrine tumours (eg. radiolabeled tryptophan) may provide improved resolution and detection of metastatic disease.

Histological Diagnosis

Histological diagnosis is essential to appropriate staging and management of GEP-NETs. Endoscopic biopsy is frequently done but may not be possible for small bowel or pancreatic NETs.


Staging is dependent on tumour site; different staging systems are used for gastric, pancreatic, small bowel, and large bowel NETs.