Neuro-endocrine tumours

Tumours derived from neuro-endocrine or chromaffin cells. These may occur in isolation or as part of MEN1 or neurofibromatosis. The diagnosis carcinoid syndrome refers to the association of diarrhoea and flushing associated with peptide secretion from these tumours.

Consider referral to clinical geneticist for counselling, DNA testing and family screening

If the diagnosis of MEN1 or neurofibromatosis is clinically likely, for example in the presence of skin changes or with hyperparathyroidism or pituitary disease, discuss genetic testing.

Baseline investigations - all patients

Full blood count

Anaemia is a non specific marker of malignancy and always requires further investigation. B12 deficiency suggests terminal ileal disease.

Urea and electrolytes

Hypokalaemic acidosis may occur with severe diarrhoea, for example due to VIPoma.

Hyponatraemia may occur with salt and water depletion.

Liver function test

Useful indicator of possible liver metastases.

Bone profile

Hypercalcaemia may occur with neuro-endocrine tumours, with metastic disease or with associated hyperparathyroidism in MEN1.

Fasting glucose and HbA1c

These are useful baseline measurements. Hypoglycaemia raises the possibility of an occult insulinoma, and may occur with glucocorticoid deficiency or metastatic disease.

Many pancreatic neuro-endocrine tumours lead to glucose intolerance, for example glucagonomas.

Fasting gut hormones

Gut hormones should be documented as soon as a neuro-endocrine tumour is suspected and may provide a useful indicator of disease burden following treatment.

This needs to be performed after a 12 hour fast with a concurrent sample for urea, electrolytes and calcium. This test should include chromogranin A and B, vasoactive intestinal peptide VIP, somatostatin, glucagon, gastrin, pancreatic polypeptide PP and neurotensin.

Proton pump inhibitors need to be stopped for at least two weeks, and H2 (histamine 2 receptor) antagonists stopped for at least three days prior to testing where possible, and a complete medication list is required for interpretation of results.

2x24hr urinary 5-hydroxyindole acetic acid

Urinary 5-hydroxyindole acetic acid is a metabolite of serotonin produced by carcinoid tumours. It is detectable in the urine in metastatic disease.

False positives may occur with certain foods, for example bananas, avocado, aubergine, nuts and tomatoes, as well as various cough and cold preparations.

Baseline pituitary function

When a NET is confirmed, basal pituitary function should be documented due to the association with pituitary tumours in MEN1. Further tests should be considered if indicated. ACTH and other pituitary and hypothalamic peptides may also be secreted by NETs.

Testing should include prolactin, 9am cortisol, thyroid stimulating hormone, free thyroxine, growth hormone, insulin like growth factor-I, luteinising hormone, follicle stimulating hormone, sex hormone binding globulin and estrodiol/testosterone.

Further investigations - selected cases only

Fasting insulin and C-peptide

Full investigation for possible insulinoma requires a supervised fast.

Chest radiograph

This should be performed at baseline as a screen for malignant disease, for thymic or bronchial lesions, for cardiac complications and prior to considering surgery.

Electrocardiogram

ECG should be performed in all patients at baseline to document and confirm any arrhythmias or other changes.

Echocardiogram

This should be performed at baseline and repeated if clinically indicated or on an annual basis in a patient with a functioning NET or carcinoid syndrome.

CT abdomen, chest and pelvis

CT or MRI scanning of the abdomen, chest and pelvis should be performed in all cases of confirmed NET to locate the primary, and to stage metastatic disease. Fifty percent of NETs arise within the small bowel or pancreas.

Abdominal and endoscopic ultrasound

Ultrasound imaging will often provide further useful anatomical information for example if cysts are suspected. 

Endoscopic ultrasound can also identify tiny pancreatic lesions and provide further detailed anatomical information about the pancreas.

Barium small bowel follow through

Barium examination may be useful in possible sub acute bowel obstruction, or to aid localisation of the primary tumour.

Oesophagogastroduodenoscopy

If the patient complains of severe upper gastrointestinal symptoms suggestive of peptic ulcer disease, or has other warning features, for example anaemia or weight loss, direct visualisation of the upper gastrointestinal tract is essential.

OGD with follow through or push enteroscopy may also be performed to locate and allow biopsy of small bowel lesions.

Selective venous sampling of the pancreas

Selective angiography, with calcium infusion to stimulate peptide secretion during sampling, may be performed to aid precise localisation of biochemically proven functioning lesions and to define anatomy prior to pancreatic surgery.

Meta-iodobenzylguianidine scan

This is usually performed to aid localisation of NETs, and to detect metastatic disease prior to surgery.

Octreotide uptake scan

This may also be performed to aid localisation of NETs, particularly if they are not obvious on MIBG scanning.

Parathyroid hormone

Parathyroid hormone should always be tested in the patient with hypercalcaemia.

If elevated, this implies parathyroid disease and MEN1 which should be investigated and treated appropriately, rather than tumour associated hypercalcaemia.

Vitamin D

Useful to document vitamin D levels to aid interpretation of serum calcium and PTH levels.

MRI pituitary

This should be performed in all cases of MEN1 at diagnosis, or if pituitary disease is suspected.

2x24hr urinary metanephrines

Although phaeochromocytoma is not usually associated with NETs, screening should be performed at the slightest suspicion, since it is a life threatening condition, and its presentation can be confusing.