Introduction: In neuroendocrine tumours (NETs), the urinary concentration of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) is used to monitor disease progression or treatment response. The sensitivity and specificity in the presence of the carcinoid syndrome are approximately 70 and 90%, respectively. Collecting a 24 hour urine specimen is difficult and inconvenient for patients and increases analytical variability. In addition, serotonin-containing foods may increase urinary 5-HIAA levels and require food avoidance. Aim of the study: To assess the correlation between 5-HIAA concentration in a spot-urine sample with the 24 h-urine collection.
Methods: Patients with NETs or symptoms suggestive of NETs seen in our Endocrine-Oncology Clinic provided a 24 h-urine collection and a spot-urine for 5-HIAA assessment. Patients were advised to avoid serotonin-rich food for three days prior and during the collection period. Urine 5-HIAA was analysed by high-performance liquid chromatography (HPLC). Different laboratories give upper reference values for 5-HIAA excretion of 40 to 50 μmol/24 h depending on the laboratory. As suggested by the Kings Hospital London group, a cut-off value of 5 μmol/mmol for spot urinary 5-HIAA was used as the upper reference limit.
Results: We included 130 paired samples from 108 patients: 61/108 were male, the mean age was 64.5y (SD 14.2) years, and 97/108 had a NET diagnosis: 74/130 (56.9%) measurements were ≥40 μmol/24 h (median concentration 50.5 μmol/24 h, IQR 26.75 to 145.5) and 63/130 (48.5%) from spot specimens were ≥5 mol/mmol (median concentration 4.69, IQR 2.26 to 16.4). A spot-urine was concordant with 24 h-urine results in 85% (κ 0.71). The Spearmans correlation between 5-HIAA measured in the 24 h-urine and the spot-urine was +0.863 (P<0.001). Using the 24 h-urine collection as a gold standard, the spot-urine had a sensitivity of 79.7% and a specificity of 92.9%. Based on the ROC-curve, a sensitivity of 95% was reached using 5.3 as cut-off point for the spot-urine. Using 50 μmol/24 h as upper normal range value for 5-HIAA, the sensitivity was 87.9% and the specificity 92.2%.
Conclusions: These results suggest that the spot-urine is a simple and promising sample type for 5-HIAA analysis, in particular for follow-up in patients with known elevated 5-HIAA levels.
05 Dec 2016
UK and Ireland Neuroendocrine Tumour Society