Neuroendocrine tumours Flashcards
What do neuroendocrine cells contain
neurotransmitters
neuromodulators
neuropeptide hormones with secretory granules
What are the differences between neurones and neuroendocrine cells
Neuroendocrine cells do not have axons and don’t make synapses
What does the gastroenteropancreatic neuroendocrine system provide
the richest source of regulatory peptides outside the brain
Where do neuroendocrine tumours originate from
neuroendocrine cells within the gut (75%)
pancreatic islet cells (5%)
lungs (15%)
Other organs)
What are neuroendocrine tumours classified according to
Their embryological origin
What determines whether a neuroendocrine tumour is functioning or non-functioning
whether a secreted hormone is detectable and associated symptoms are present
What are neuroendocrine tumours sometimes part of
familial syndromes such as MEN1 or MEN2
neurofibromatosis type 1
What is the term carcinoid used for
NETs mostly derived from serotonin-producing enterochromaffin cells
What does the classification of NETs into benign and malignant depend on
tumour size, local spread, vascular invasion, metastases nuclear atypic
Mutations in what gene are the most common form of genetic predisposition to NETs
MEN 1
How might a gastroenteropancreatic tumour present
may be asymptomatic or may present with obstructive symptoms due to tumour bulk (pain, nausea, vomiting)
What is carcinoid syndrome
it is usually a result of metastases to the liver with the subsequent release of hormones (serotonin, tachykinins and other vasoactive compounds) into the systemic circulaiton
What is carcinoid syndrome characterised by
flushing
diarrhoea
occasionally wheezing
What is pellagra
niacin deficiency
What is pellagra characterised by
dermatitis
glossitis
diarrhoea
dementia
Why might muscle wasting occur
as a result of poor protein synthesis
What is carcinoid heart disease characterised by
deposits of fibrous tissue on the endocardium of the valvular cusps and cardiac chambers
What is a carcinoid crisis characterised by
progound flushing
bronchospasm
achycardia
fluctuating blood pressure
What might precipitate the carcinoid crisis
anaesthetic induction
intraoperative handling of the tumour
invasive therapeutic procedures such as embolisation and radio frequency ablation
What are the symptoms of insulinoma
hypoglycaemia: sweating, dizziness, tachycardia, weakness, confusion, unconsciousness
symptoms relieved on eating
What are the symptoms of gastronome
severe peptic ulceration and diarrhoea
What are the symptoms of glucagonoma
necrolytic migratory erythema (rash affecting the lower abdomen, buttocks, perineum and groin
Weight loss
diabetes mellitus
stomatitis
What are symptoms of VIPoma (Wener-Morrison syndrome)
profuse watery diarrhoea with marked hypokalaemia
What are symptoms of stomatostatinoma
cholelithiasis weight loss diarrhoea steatorrhoea diabetes mellitus
What should patients with NETs be searched for
MEN 1
MEN 2 and
NG 1
What is the gold standard investigation for gastroenteropancreatic NETs
detailed histology
What biochemical tests should be done for patients with symptoms suspicious of gastroenteropancreatic NET
Plasma chromogranin A
24 hour urinary 5- hydroxyindoleacetic acid
fasting gut hormone profile
What factors can affect urinary 5-hydrozyindoleacetic acid excretion
bananas avocados aubergines pineapples plums walnuts caffeine paracetamol naproxen
What is chromogranin A
a large protein that is produced by all cells deriving from the neural crest
What is the main metabolite of serotoning secretion
5-HIAA
What should be measured prior to giving glucose in suspected insulinoma
Insulin and C-peptide levels
What is diagnostic of an insulinoma
elevated plasma insulin and c peptide levels in the presence of hypoglycaemia
Plasma glucose of less than 2.2
What are the investigations for a suspected gastrinoma
fasting gastrin level and gastric secretion studies
What must the patient not be taking in order to accurately measure gastrin in a patient with a suspected gastronome
PPI (2 weeks)
histamine 2 blockers (3 days)
What is the most sensitive modality in assessing secondaries
SRS (somatostatin receptor scintigraphy)
What does treatment fr NETs depend on
symptoms
stage of disease
degree of uptake of radionuclide
histological features
What is the curative treatment for NETs
surgery
How is a potential carcinoid crisis prevented
IV infusion of octreotide at a dose of 50g per hour for 12 hours prior to and at least 48 hours after surgery
How do somatostatin analogues work in NETs
They inhibit the release of various peptide hormones in the gut and antagonise growth factor effects on tumour cells
What are some side effects of somatostatin analogues
gall stones gall bladder dysfunction fat malabsorption vitamin A and D malabsorption headaches diarrhoea dizziness hyperglycaemia
What are some side effects of alpha-interferon
Flu like symptoms weit loss fatigue depression hepatotoxicity autoimmune disorders
Who is hepatic artery embolisation indicated for
patients with non-resectable Multiple or hormone secreting tumours
How does artery embolisation work
It induces ischaemia of the tumour cells thereby reducing their hormone output and causing liquefaction
What is the most common side effect of artery embolisation
post embolisation syndrome (nausea, fever, abdominal pain)
What is the overall 5 year survival of all NET cases
67%
What is MEN characterised by
tumours involving two or more endocrine glands within a gins patient
How are MEN syndromes inherited
autosomal dominant
What is MEN type 1 characterised by
predisposition to:
parathyroid adenomas
enteropancreatic endocrine adenomas
pituitary adenomas
What do parathyroid adenomas result in
primary hyperparathyroidism and hypercalcaemia
What are the majority of pituitary adenomas that occur in MEN1 patients
prolactinomas
What does MEN1 encode for
protein called renin
What does renin do
suppresses gene transcription activated by JunD and control cells proliferation
What is found in 95% of patients with MEN1
germline inactivating mutations in the tumour suppressor gene MEN 1 (chromosome 11)
What biochemical eating should be done for MEN1
serum calcium
prolactin
measurement of gut hormones
What is the management of MEN1
subtotal parathyroidectomy for hyperparathyroidism
surgical resection of pancreatic NETs
What does MEN2 result from
germline mutations in the RET protooncogene (chromosome 10) which encodes a tyrosine kinase receptor
what endocrine tumours are associated with MEN 2
Medullary thyroid cancer (MTC)
phaeochromocytoma
parathyroid adenomas
What is the ideal treatment of MEN 2
Total thyroidectomy
Describe the differences in hyperparathyroidism in MEN1 and MEN2
It is milder in MEN2
More than 1 parathyroid gland is enlarged in MEN2
What is MEN2
association of medullary thyroid cancer (MTC) with pheochromocytoma
