Received on January 30, 2004
Accepted on June 18, 2004

Endocrinology and Metabolism

Daily Cyclic Changes in the Urinary Excretion of 5-Hydroxyindoleacetic Acid in Patients with Carcinoid Tumors

¹ Departments of Gastroenterology, Clinical Chemistry, and Statistics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, and Gastroenterology
² Departments of Gastroenterology, Clinical Chemistry, and Statistics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, and Clinical Chemistry
³ Departments of Gastroenterology, Clinical Chemistry, and Statistics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, and Statistics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
⁴ Departments of Gastroenterology, Clinical Chemistry, and Statistics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, and Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands

^* To whom correspondence should be addressed. E-mail: j.zuetenhorst{at}nki.nl.

Background: Vasoactive peptides produced by neuroendocrine tumors can induce characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and wheezing). To what extent external factors provoke these symptoms and how 5-hydroxyindoleacetic acid (5-HIAA) excretion (the degradation product of serotonin) varies throughout the day remain unknown. In this study, we investigated whether symptoms and daily activity are related to 5-HIAA excretion and whether 24-h urine collection is needed.

Methods: In 26 patients with metastatic carcinoid (14 men and 12 women; median age, 60 years) urine was collected in portions of 4 or 8 h during 2 days. Patients were asked to keep a diary in which they noted symptoms of flushes, consistency of stools, activities, and food intake.

Results: Excretion of 5-HIAA in 24-h urine was increased in 88% of the patients (median, 515 µmol/24 h). Overnight-collected urine appeared the most representative for 24-h collection concentrations (correlation coefficient = 0.85). We found no clear correlation between symptoms of the carcinoid syndrome and degree of activity. Watery diarrhea was reported only by patients with strong variations in 5-HIAA excretion. One-half of the patients (n = 16) exhibited a high variability in urinary 5-HIAA excretion throughout the day, with increased concentrations most prominent in morning collections (P = 0.0074) and lower concentrations in the evening (P = 0.0034). In the other patients these curves were flat.

Conclusions: Cyclic changes in patients relate to high variability in 5-HIAA excretion. Overnight collected urine can replace the 24-h urine collection, and strong variations in 5-HIAA excretion seem to be associated with severity of diarrhea.