carcinoid syndrome

Question 1

definition

Answer 1

carcinoid = slow growing tumour originating from neuroendocrine cells
carcinoid tumours of the midgut (jejunum, ileum, appendix, and cecum) are associated with the carcinoid syndrome

Carcinoid syndrome occurs due to release of serotonin (5-hydroxytryptamine) and other vasoactive peptides into the systemic circulation from a carcinoid tumour. Twenty percent to 30% of midgut neuroendocrine tumours (NETs), 5% of bronchial carcinoid tumours, and approximately 1% of pancreatic NETs secrete 5-hydroxytryptamine and other peptides. In patients with these tumours, carcinoid syndrome develops. The principal features of carcinoid syndrome are diarrhoea and flushing. Wheezing, telangiectasia, and abdominal pain can also occur.

Question 2

pathophysiology

Answer 2

Neuroendocrine tumours normally secrete biogenic amines into the circulation. However, when the primary site is within the gut, the secreted amines are degraded by the liver and symptoms do not generally occur. When liver metastases are present, these amines drain into the circulation prior to being broken down and, hence, cause carcinoid syndrome.[8] The most prominent secretory products of carcinoid tumours are amines, kallikrein, and prostaglandins. One of these amines is serotonin. Normally serotonin is synthesised from tryptophan and is subsequently metabolised by monoamine oxidase to 5-hydroxyindoleacetic acid, which is subsequently secreted in the urine.[9] In healthy people, approximately 99% of tryptophan is used for the synthesis of nicotinic acid and <1% is converted to serotonin. However, in patients with carcinoid tumours there is a shift towards the production of serotonin. The increased production of serotonin and other products and their direct release into the systemic circulation, due to liver metastases, leads to the development of carcinoid syndrome.

Question 3

signs and symptoms

Answer 3

diarrhoea 
flushing 
palpitations
abdominal cramps 
telangiectasia 
signs of right heart failure (carcinoid heart disease)
cardiac murmurs (serotonin and kinins lead to fibrosis of right sided heart valves)
hepatomegaly (presence of liver mets)

• wheeze (with bronchial carcinoids but not really midgut carcinoids)
• pellagra (tryptophan is used to make more serotonin, so less is used to make niacin. so there is niacin deficiency which causes pellagra -> diarrhoea, dermatitis, dementia)
• abdo masses

Question 4

risk factors

Answer 4

genetic multiple endocrine neoplasia type 1 (MEN-1) syndrome associated with neuroendocrine tumours —- but weak risk factor!

Question 5

investigations

Answer 5

1st investigations:

• serum chromogranin A/B => elevated
• urinary serotonin (5-hydroxyindoleacetic acid) => elevated
• metabolic panel => elevated creatinine if dehydrated from diarrhoea
• LFTs => may be deranged depending on tumour site
• FBC => usually normal

others:

• CT chest, abdo, pelvis with dual-phase liver (for cancer staging/progression)
• bronchoscopy
• endoscopy
• somatostatin receptor scintigraphy +/- somatostatin SPECT (identify areas of somatostatin receptor positive tumour for treatment options)
• iodine I 123 MIBG scintigraphy (find areas of MIBG take up which indicates neuroendocrine tumour)
• histology
• PET