Comparison of Serum and Urinary 5-Hydroxyindoleacetic Acid as Biomarker for Neuroendocrine Neoplasms

Abstract

Context Patients with serotonin-secreting neuroendocrine neoplasms (NENs) have increased serum 5-hydroxyindoleacetic acid (5HIAA) concentrations. Serum 5HIAA thus serves as a biomarker in NEN. Objective To evaluate an improved tandem mass spectrometric serum 5HIAA assay for diagnosis and follow-up of NEN in a clinical cohort. Design A retrospective study during 2016-2018 at the Diagnostic Center and Department of Endocrinology at Helsinki University Hospital, Finland. Methods Detailed patient data was obtained from 116 patients. Serum 5HIAA was analyzed by 2 different liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays with samples prepared either by protein precipitation or solid phase extraction. Twenty-four–hour urine 5HIAA samples (n = 33) were analyzed by amperometric LC, and the results were compared. Specificity and sensitivity were calculated by receiver operating characteristic (ROC) analysis. Results We achieved 5 to10 000 nmol/L linearity and ≤2.5% variation with our new serum 5HIAA assay. In ROC analysis, the area under curve was 85% by serum assays [upper reference limit (URL) value 123 nmol/L] and 88% by the 24-h urine 5HIAA assay (URL value of 47.1 µmol), respectively. A difference (P < 0.001) between patients with active NEN and patients in remission was found by all 5HIAA assays. Conclusion Serum 5HIAA by LC-MS/MS after protein precipitation performs equally well for the diagnosis of NEN as urinary 5HIAA LC assay. The outcome and sensitivity for serum and 24-h urine assays are convergent. Due to much more reliable and convenient sampling, we recommend serum instead of 24-h urine 5HIAA for diagnosis and follow-up of NEN patients.