Carcinoid syndrome

Question 1

Define carcinoid syndrome.

Answer 1

A paraneoplastic syndrome secondary to carcinoid tumours.

The syndrome includes flushing and diarrhoea, and less frequently, heart failure, vomiting and bronchoconstriction. It is caused by endogenous secretion of mainly serotonin and other vasoactive peptides.

Question 2

What is a carcinoid tumour?

Answer 2

Carcinoid tumor is a slow-growing type of neuroendocrine tumour originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors usually begin in the digestive tract (stomach, appendix, small intestine, colon, rectum) or in the lungs.

Question 3

What is the aetiology of carcinoid syndrome?

Answer 3

Neuroendocrine tumours (NETs) which arise from endocrine cells –> hormonal peptide and bioactive substance release

4% of NETs are functional

• 20-30% of midgut carcinoids –> CS
• 5% of bronchial carcinoids –> CS
• 1% of foregut carcinoids –> CS
• hindgut tumours are generally non-functional and do not cause CS
• 95% of NET liver metastases cause CS
• CS can also be caused by serotonin or tachykinin production from retroperitoneal metastases or ovarian tumours which bypass liver and enter systemic circulation

Question 4

What is the pathophysiology of carcinoid syndrome?

Answer 4

Most important point: usually occurs when metastases are present in the liver and release serotonin into the systemic circulation

• NETs release biogenic amines into circulation e.g. serotonin*, kallikrein, prostaglandins
• When the primary site is the gut, the amines get degraded by the liver and symptoms do not generally occur
• When liver metastases are present amines drain into circulation before being broken down -> carcinoid syndrome

Tryptophan –MAO–> 5-HIAA –> secreted in urine

99% of tryptophan is usually used for nicotinic acid synthesis but in carcinoid tumours there is a shift towards serotonin which gets released to circulation due to liver metastases

Question 5

What are the signs ad symptoms of carcinoid syndrome?

Answer 5

Symptoms:

• Diarrhoea - with no precipitating factor
• Flushing
• Reddening of the face
• Abdominal pain - liver mets –> hepatomegaly
• Weight loss
• Symptoms worsen with stress, exercise, not tolerating alcohol, chocolate and bananas.
• Palpitations

Signs:

• Murmurs - serotonin and kinins leading to fibrosis of right heart valves
• Right heart failure - peripheral oedema ,elevated JVP
• Abdominal mass
• Wheeze in bronchial carcinoids
• Telangiectasias

Question 6

What foods worsen carcinoid syndrome symptoms?

Answer 6

Tyramine containing foods and alcohol

Question 7

Which receptor is commonly found in carcinoid tumours and be used in uptake imaging?

Answer 7

Somatostatin receptor type 2 is present in 70% to 90% of carcinoid tumours

Question 8

What investigations would you do for carcinoid syndrome?

Answer 8

• urinary 5-HIAA - elevated
• plasma chromogranin A y

Other:

• Creatinine - elevated in dehydration
• LFTs - variable; AST/ALT elevated.
• Normal FBC
• Ga-86 DOTATATE PET - sensitive for somatostatin receptor-positive tumours
• MIBG scintigraphy - endocrine cells take up the compound
• SPECT - identifies somatostatin receptor-positive tumour.
• CT liver/ bronchoscopy/endoscopy

Question 9

Summarise the management of carcinoid syndrome.

Answer 9

• Surgical resection
• Octreotide infusion peri-operative - prevents carcinoid crisis
• Diarrhoea - cyproheptadine may help
• Radiofrequency ablation
• If not suitable for surgery - somatostatin analogue/interferon alfa (octreotide)

Question 10

Name a risk factor for carcinoid syndrome.

Answer 10

MEN-1 syndrome - NETs are associated with MEN-1 in about 10% of cases but few of these cause carcinoid syndrome

Question 11

What are the complications of carcinoid syndrome?

Answer 11

Carcinoid heart disease - usually fibrosis as well as affecting valves

Bowel obstruction or intestinal bleeding

Carcinoid crisis

Pellagra i.e. diarrhoea, dermatitis, and dementia; because tryptophan is required to produce niacin