Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations

Abstract

ContextBiogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours.ObjectiveTo re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays.MethodsBibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences.Results5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.).ConclusionRevisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays.

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

“…Indole-3-carboxaldehyde (indole-3-aldehyde), a gut microbiota-derived indole derivative of tryptophan catabolism produced by the action of Lactobacillus-encoded tryptophanase inhibits inflammation through activation of the aryl hydrocarbon receptor in lymphoid cells 62 . Finally, 5-hydroxyindole-3-acetic acid is the most abundant end product of both central and peripheral enzymatic degradation of serotonin 63 . Although the direct biological activity of 5-hydroxyindole-3-acetic acid is yet to be documented; its excessive production by endocrine and neuroendocrine tumors 63 and the large quantities of reactive oxygen species that are produced during its biosynthesis from serotonin 64 might explain its association with systemic inflammation.…”

“…Finally, 5-hydroxyindole-3-acetic acid is the most abundant end product of both central and peripheral enzymatic degradation of serotonin 63 . Although the direct biological activity of 5-hydroxyindole-3-acetic acid is yet to be documented; its excessive production by endocrine and neuroendocrine tumors 63 and the large quantities of reactive oxygen species that are produced during its biosynthesis from serotonin 64 might explain its association with systemic inflammation. Epidemiological studies have reported associations between proinflammatory state among adolescents and young adults and an increased risk of future cardiovascular diseases 65 , thus the amino acids associated with elevated CRP in the present study could be biomarkers of proinflammatory phase leading to the development cardiovascular diseases.…”

Carcinoid Syndrome: A Review

“…When measured in a 24-hour urine sample, 5-HIAA level has a sensitivity of 73% and a specificity of 100% for diagnosing carcinoid [22]. Urine 5-HIAA can also be detected in people who eat food rich in tryptophan, to prevent these false-positive results one should abstain from tryptophan-containing foods 72 hrs before the test [23].…”

The Diagnosis of Neuroendocrine Tumours: An Endocrine Perspective

“…Urinary 5-HIAA values may found to be normal in non-metastatic tumours, in patients with CS who possibly secrete other biologically-active molecules, and rarely in some CS patients without diarrhoea, while a small number of normal individuals may have elevated urinary 5-HIAA (probably due to diet) (23). It may be used both for diagnosis and follow-up but it has weak cor- Moderate elevations due to foods that contain serotonin and tryptophan-bananas (23,25,38,224), plantains (38,224), pineapple (23,25,38,224), kiwis (38,224), walnuts (23,224), almond (224), cashews (224), macadamia nuts (224), plums (23,38,224), tomatoes (38,224), tomato products (38,224), avocado (23,25,38,224), pecans (23), cantaloupe (38), dates (38), grapefruit (38), honeydew melon (38), meat, milk, cheese, chocolate (23), tea and coffee (23), black olives (38), spinach (38), broccoli (38), cauliflower (38) heparin (23,25,38), imipramine (23,38), isoniazide …”

“…Conditions that increase 5-HIAA-Untreated patients with malabsorption (celiac disease, tropical sprue, Whipple disease, intestinal stasis, cystic fibrosis) Table 5. The foods and medications that should be avoided 72 hs prior to the test and conditions that affect 5-HIAA collection result are listed below (recommendations differ and the list below may not be definitive) (23,25,38,40,45,224,225). To avoid degradation, preservatives should be used (generally hydrochloric acid) to keep the pH around 3 (224).…”