Serum 5-Hydroxyindoleacetic Acid Measurements for the Diagnosis and Follow-up of Carcinoid Syndrome

Abstract

Context: The biochemical diagnosis of carcinoid syndrome (CS) is 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.

Objective: To assess the diagnostic value of serum 5-HIAA measurements in patients with CS.

Design: Retrospective cohort study.

Setting: Tertiary care hospital.

Patients: 379 patients with a neuroendocrine tumor (NET), of whom 136 (35.9%) had CS; 153 control samples were included.

Intervention: Paired serum and 24-hour urine 5-HIAA measurements.

Main outcome measure(s): Performance of serum and 24-hour urine 5-HIAA for the diagnosis of CS, measured by area under the receiver operating characteristic curve (AUROC).

Results: Serum 5-HIAA performance was similar to that of 24-hour urine 5-HIAA for the diagnosis of CS in the total NET cohort (n = 379, AUROC 0.824 vs 0.843, P = .50) and in a subgroup of somatostatin analog (SSA)-naïve patients (n = 141, AUROC 0.915 vs 0.938, P = .66). Optimal cutoff value of serum 5-HIAA for the diagnosis of CS was 139.4 nmol/L (sensitivity 96.3%, specificity 87.6%) as determined in a subgroup analysis of SSA-naive patients with CS and controls. Serum 5-HIAA correlated well with 24-hour urine 5-HIAA (r = 0.892, P < .001) and the presence of flushing, diarrhea, and carcinoid heart disease (odds ratio 1.047-1.073 for every 100 nmol/L increase, P < .001).

Conclusion: Serum 5-HIAA measurements are equivalent to 24-hour urine 5-HIAA measurements for the diagnosis of CS in patients with NET and form an accessible alternative.

Keywords: 5-hydroxyindoleacetic acid; SSA; biomarker; carcinoid syndrome; neuroendocrine tumor.