Fasting plasma 5-hydroxyindolacetic acid (5-HIAA) correlates with 24-hour urinary 5-HIAA; evaluation of a simpler assessment of 5-HIAA

Background: Research has shown that decreasing serotonin, as reflected by 5-hydroxyindolacetic acid [5-HIAA], is associated with clinical improvement in carcinoid syndrome (CS) patients. Collection of 24-hour urine samples is standard practice to assess 5-HIAA excretion in carcinoid syndrome patients, but samples are often incomplete, time-consuming, and typically cumbersome for patients to collect. This analysis was done to compare plasma to urine 5-HIAA [u5-HIAA] to determine if a single blood sample can be used to accurately assess 5-HIAA in place of a 24-hour urine collection. Methods: A phase 1 study of LX1033, a serotonin synthesis inhibitor (SSI) that reduces peripheral serotonin, was conducted in 32 healthy individuals (24 subjects received daily doses ranging from 750 to 2250 mg LX1033/day for 14 days; 8 subjects received placebo). Study participants were housed in a clinical research unit for 17 days. Daily fasting plasma and 24-hour urine samples were obtained for analysis of 5-HIAA. Samples were paired by subject and time point for statistical analysis. Pearson's correlation coefficients were calculated and tested for statistical significance on these paired sample values. Results: A total of 409 paired samples were analyzed. Correlations were statistically significant based on observed values for all treatment groups. Analysis of correlations based on change from baseline 5-HIAA paired values also showed statistically significant results, p<0.001. Conclusion: This study demonstrates that fasting plasma 5-HIAA was significantly correlated with u5-HIAA. Plasma samples are well controlled compared to 24-hour urine collections and offer a more convenient research tool for assessing temporal 5-HIAA. (Table Presented).