Carcinoid tumour marker tests - 5-hydroxyindoleacetic acid urine

Role

24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA), the major serotonin breakdown product, is the standard biochemical test for suspected carcinoid syndrome - elevated in the setting of a serotonin-secreting neuroendocrine tumour with sufficient tumour burden or hepatic metastases to overwhelm hepatic serotonin clearance
Used specifically in patients presenting with the clinical carcinoid syndrome triad (flushing, diarrhoea, and in advanced disease, right-sided cardiac valve disease) rather than as a routine screen for asymptomatic neuroendocrine tumours

Carcinoid tumours (most commonly small bowel/appendiceal in origin) secrete serotonin, which is normally metabolised by the liver on first pass - carcinoid syndrome (and detectable 5-HIAA elevation) typically only manifests once hepatic metastases develop, bypassing first-pass hepatic clearance and allowing serotonin to reach the systemic circulation in sufficient quantity to cause symptoms

Dietary interference is a significant pre-analytical pitfall - serotonin-rich foods (bananas, avocados, tomatoes, walnuts) and certain medications can cause false-positive elevation, requiring dietary restriction before and during the 24-hour collection for accurate results
A single random/spot measurement is less reliable than the standard 24-hour collection given diurnal variation in serotonin metabolite excretion

Elevated 5-HIAA with compatible clinical syndrome supports the carcinoid diagnosis and directs further localisation imaging (CT/MRI, somatostatin receptor imaging) and consideration of somatostatin analogue therapy (which both controls symptoms and has anti-proliferative activity)
Serial 5-HIAA levels can be used to monitor treatment response and disease progression once a diagnosis is established

Carcinoid syndrome (flushing, diarrhoea, right heart valve disease from serotonin exposure), hepatic metastases as the trigger for symptomatic disease, dietary pre-analytical interference, somatostatin analogue therapy
Carcinoid syndrome symptoms and elevated 5-HIAA typically only appear once hepatic metastases have developed, since the liver normally clears secreted serotonin on first pass before it reaches the systemic circulation - a primary carcinoid tumour without hepatic spread is therefore often biochemically silent despite the tumour being present

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