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.
Neuro-endocrine tumours may be diagnosed unexpectedly on a histological specimen, may present with 'carcinoid syndrome', where symptoms are due to the release of specific peptides, or as a malignant but clinically non functioning mass 'carcinoid tumours'.
Weight loss and anorexia may occur with any malignancy and are characteristic features of glucagonomas.
Diarrhoea and steatorrhoea may occur in any pancreatic tumour, or secretory neuro-endocrine tumour (NET), and classically occur with 5HIAA or gastrin secretion.
Very large volumes of watery non steatorrhoea diarrhoea is suggestive of a VIP secreting tumour.
Changes in bowel habit may accompany any gastrointestinal malignancy including NETs due to local effects and warrants dedicated investigation, usually with direct endoscopic examination.
Diarrhoea is typical secondary to peptide hormone release.
Constipation is typical with hypercalcaemia either due to parathyroid hormone related peptide (PTHrP) release, metastatic disease, or associated hyperparathyroidism in MEN1.
Subacute bowel obstruction is frequently seen with gastrointestinal NETs due to a desmoplastic reaction in the mesentery.
Gall stones are a classic feature of somatostatin secreting tumours, in association with diabetes, and steatorrhoea. Fifty percent of somatostatinomas occur in patients with neurofibromatosis type 1.
Phaeochromocytoma may present with abdominal pain and may occasionally be associated with NETs in MEN1.
VIP secreting tumours cause profound watery diarrhoea as well as hypochlorhydria. This may lead to dehydration, weakness and hypokalaemic acidosis.
Typical 'carcinoid' flushing is a spontaneous unpleasant feeling of heat rising up through the body, associated with flushing - deep red colouration of the skin which may become permanent.
It is not associated with sweating, which may help differentiate it from menopausal symptoms. No triggers or particular timing can usually be identified.
Elevated 5HIAA levels are frequently observed in patients who flush, although the flushing may be due to many different peptides for example VIP.
Carcinoid flushes may be associated with acute bronchospasm and wheeze.
NET derived vasoactive peptides may also lead to cardiac valve thickening and symptoms of right heart failure.
Thrombolembolic disease is very commonly associated with glucagonomas.
This may occur with any pancreatic tumour but particularly with glucagon, VIP or somatostatin secreting tumours.
Neuro-endocrine tumours (NETs), in particular somatostanimas, may be associated with neurofibromatosis in which skin changes (neurofibromas, lipomas) are usually obvious.
Facial angiofibromas, collagenomas and lipomas may be associated with NETs in MEN1.
Deep pigmentation may occur with NET secretion of ACTH.
Glucagonomas are classically associated with skin changes in areas exposed to friction: necrolytic migratory erythema, but may also cause glossitis.
Thromboembolic disease is very commonly associated with glucagonomas.
'Funny turns' with sweating, palpitations, hunger, anxiety and confusion following a fast is suggestive of hypoglycaemia.
Weight gain also typically occurs with insulinomas.
Gastrin secretion by pancreatic tumours classically causes severe indigestion. Zollinger-Ellison syndrome, with severe dyspepsia and multiple peptic ulcers, follows gastrin secretion, which may also cause diarrhoea and steatorrhoea.
Glucagon secretion is associated with glucose intolerance or diabetes mellitus, anorexia, anaemia, glossitis, weight loss and necrolytic migratory erythema.
Thromboembolic disease is also commonly associated with glucagonomas.
High volume watery diarrhoea, with hypochlorhydria, dehydration, weakness and hypokalaemic acidosis, is a common presentation of VIP secreting tumours.
VIPomas may also cause new or worsening glucose intolerance, and flushing.
Somatostatinomas typically present with gall stones, diabetes and steatorrhoea.
Ask the patient whether there is any history of excessive thirst, nocturia, or other symptoms suggestive of renal colic.
Hyperparathyroidism is classically associated with pancreatic NETs in MEN1 though hypercalcaemia may complicate any malignancy.
Check whether there are features suggesting prolactinoma: galactorrhoea, oligomenorrhoea, erectile dysfunction or loss of libido; any visual loss or headache that might suggest a non functioning tumour; or symptoms of Cushing's or acromegaly.
Prolactinomas are the commonest pituitary tumour encountered in MEN1.
Adrenocortical tumours, meningiomas, ependymonas and leiomyomas may be associated with NETs in MEN1. Facial angiofibromas, collagenomas and lipomas may also occur in MEN1.
NETs may also occur in association with neurofibromas in neurofibromatosis type 1.