Makarious Kerolles1, Merijn Mulders1, Mina Mirzaian2, Sjoerd van den Berg1,2, Richard Feelders1, Wouter de Herder1, Johannes Hofland1
(1) Department of Internal Medicine, Section of Endocrinology, ENETS center of excellence, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands. (2) Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands.
Introduction:
The diagnosis of carcinoid syndrome (CS), the most prevalent hormonal syndrome in neuroendocrine tumor (NET) patients, is most commonly established through the measurement of 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA), but these measurements are prone to sampling error and may be troublesome for patients. Serum 5-HIAA measurements might constitute a more reliable and convenient alternative to diagnose CS.
Aim:
To assess the value of serum 5-HIAA measurements for the diagnosis of CS.
Materials and methods:
We retrospectively analyzed all NET patients at our center with a paired serum and 24-hour urine 5-HIAA measurement between 2021 and 2023. The performances of serum and 24-hour urine 5-HIAA for the diagnosis of CS were measured by area under the receiver operating characteristics curve (AUROC) analyses. The optimal cutoff value of serum 5-HIAA for the diagnosis of CS was determined in a subgroup analysis of somatostatin analog (SSA)-naïve CS patients and 153 controls using the Youden index. Additionally, the association between serum and 24-hour urine 5-HIAA and the presence of CS-related symptoms was investigated.
Results:
379 NET patients were included, of whom 136 (35.9%) had CS. Serum 5-HIAA performed equally well as 24-hour urine 5-HIAA for the diagnosis of CS in the total NET cohort (n=379, AUROC 0.824 vs. 0.843, p=0.50) and in a subgroup of SSA-naïve NET patients (n=141, AUROC 0.915 vs. 0.938, p=0.66). Optimal cutoff value of serum 5-HIAA for the diagnosis of CS was 139.4 nmol/L (sensitivity 96.3%, specificity 87.6%). Serum 5-HIAA correlated with 24-hour urine 5-HIAA (r=0.892, p<0.001) and the presence of flushing, diarrhea and carcinoid heart disease (OR 1.047-1.073 for every 100 nmol/L increase, p<0.001).
Conclusion:
Serum 5-HIAA measurements are equivalent to 24-hour urine 5-HIAA measurements for the diagnosis of CS and form an accessible alternative.