Interpretation
The Diagnosis of Carcinoid Syndrome©
Definition
Carcinoid tumours are neuroendocrine tumours that usually arise from enterochromaffin cells, which are found scattered throughout the body but occur principally in the submucosa of the intestine and main bronchi. The carcinoid syndrome is caused by systemic release of one or more of the secretory products: amines, polypeptides, and or prostaglandins.
Clinical presentation
The most common manifestations of carcinoid syndrome are vasomotor changes (flushing), gastrointestinal hypermotility (diarrhoea), bronchospasm (wheezing, dyspnoea) and hypotension.
An attack of carcinoid syndrome may be provoked by emotional stress, heat, ingestion of particular foods or alcohol, straining at stool, or exogenous stimulation with adrenaline, dopamine or gastrin.
Carcinoid crisis with severe flushing and diarrhoea leading to dehydration, hypotension, and arrhythmias, along with unconsciousness, is a potentially life threatening complication.
Tumour markers
Urinary 5 hydroxyindolacetic acid (5-HIAA), the breakdown product of serotonin, has been the gold standard for diagnosis and follow-up, of the carcinoid syndrome, for many years. The specificity of urinary 5-HIAA is almost 100%, if appropriate dietary restrictions are observed, but the sensitivity is reported to be much lower (35%). Urinary 5-HIAA levels can be influenced by food (e.g. bananas, avocados, pineapple, walnuts, tomatoes, plums and kiwifruit) consumption and some medications.
Whole blood (platelet) serotonin levels are a more sensitive marker for the detection of small amounts of serotonin. However, in cases with a high rate of serotonin excretion, serotonin in platelets reaches a maximum, limiting its use during follow-up. Elevated serotonin concentrations may also be found in paragangliomas and thrombocytopania.
Chromogranin A (CgA), in contrast to urinary 5-HIAA and platelet serotonin, can be used in the detection of functioning as well as non-functioning carcinoid tumours. Elevated CgA concentrations are not specific for neuroendocrine tumours and may also be seen in renal impairment, liver failure, inflammatory bowel disease and prostatic carcinoma. Thus its specificity is lower than urinary 5-HIAA (86%) but its sensitivity is higher (68%). Levels of CgA are correlated with tumour burden, and very high levels have been suggested to indicate a significantly worse survival rate.
Midgut carcinoid tumours produce the enzyme decarboxylase which transforms 5-hydroxytryptophan (5-HTP) into serotonin. Therefore serotonin and 5-HIAA levels maybe significantly raised. However, in carcinoid tumours of the foregut, the absence of this decarboxylase results in more modest increases of serotonin and 5-HIAA, as only partial conversion (by the kidney) of 5-HTP to serotonin occurs. In end-gut carcinoids, both the hydroxylase and decarboxylase may be absent and no 5-HTP, serotonin or 5-HIAA is produced.
In contrast CgA levels are independent of tumour location and can be used as a marker of for-, mid- and end-gut carcinoids.
To diagnosis presenting symptoms of carcinoid syndrome, 24 hour urinary 5-HIAA is recommended (with dietary restrictions). Blood CgA and serotonin levels are useful for monitoring the treatment of established disease and may also be use when 5-HIAA levels are equivocal. CgA levels may be used to establish tumour burden.
References
Lips CJM, Lentjes EGWM, Hoppener JWM. The spectrum of carcinoid tumours and carcinoid syndromes. Ann Clin Biochem (review) 2003;40:612-627.
Zuetenhorst JM,Tall BG. Metastatic Carcinoid Tumors: A Clinical Review. Oncologist (review) 2005;10(2):123-31.
Modlin IM, Kidd MM, Latich I et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005;128:1717-1751.
Reference Intervals
Adult 0.4 – 1.5 umol/L
Children 0.8 – 2.0 umol/L
Test Method
Solvent extraction, fluorescence
