Serotonin, 24 Hour, Urine
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
The diagnosis of a small subgroup of carcinoid tumors that produce predominately 5-HTP, but very little serotonin and chromogranin A
Follow-up of patients with known or treated carcinoid tumors that produce predominately 5-HTP, but very little serotonin and chromogranin A
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Serotonin, 24 Hr, U
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Plastic, 10-mL urine tube (Supply T068)
Specimen Volume: 5 mL
1. Collect urine for 24-hours.
2. Add 25 mL of 50% acetic acid as preservative at start of collection.
3. Refrigerate specimen during collection.
4. Patients should not eat avocados, bananas, butternuts, cantaloupe, dates, eggplant, grapefruit, hickory nuts, honeydew melon, kiwifruit, melon, nuts, pecans, pineapple, plantains, plums, tomatoes, or walnuts, which are high in serotonin for 48 hours before or during collection.
1. 24-Hour volume is required.
2. See Urine Preservatives in Special Instructions for multiple collections.
Urine Preservative Collection Options
50% Acetic Acid
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Urine||Frozen (preferred)||14 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Serotonin (5-hydroxytryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin production sites are the central nervous system (CNS), where it acts as a neurotransmitter, and neuroectodermal cells, chiefly gastrointestinal (GI) enterochromaffin cells (EC-cells). The CNS and peripheral serotonin pools are isolated from each other. EC-cell production accounts for 80% of the body's serotonin content.
Many different stimuli can release serotonin from EC-cells. Once secreted, in concert with other gut hormones, serotonin increases GI blood flow, motility, and fluid secretion. On first pass through the liver 30% to 80% of serotonin is metabolized, predominately to 5-hydroxyindoleacetic acid (5-HIAA), which is excreted by the kidneys. Ninety percent of the remainder is metabolized in the lungs, also to 5-HIAA. Of the remaining 10%, almost all is taken up by platelets, where it remains until it is released during clotting, promoting further platelet aggregation.
The main diseases that may be associated with measurable increases in serotonin are neuroectodermal tumors, in particular tumors arising from EC-cells, which are termed carcinoids. They are subdivided into foregut carcinoids, arising from respiratory tract, stomach, pancreas, or duodenum (approximately 15% of cases); midgut carcinoids, occurring within jejunum, ileum, or appendix (approximately 70% of cases); and hindgut carcinoids, which are found in the colon or rectum (approximately 15% of cases). The enzyme 5-HTP decarboxylase, which converts the intermediate 5-HTP to serotonin, is present in midgut tumors, but is absent or present in low concentrations in foregut and hindgut tumors.
Carcinoids display a spectrum of aggressiveness with no clear distinguishing line between benign and malignant. The majority of carcinoid tumors do not cause significant clinical disease. Those tumors that behave more aggressively tend to cause nonspecific GI disturbances, such as intermittent pain and bloating, for many years before more overt symptoms develop. In advanced tumors, morbidity and mortality relate as much, or more, to the biogenic amines, chiefly serotonin, and peptide hormones secreted, as to local and distant spread. The symptoms of this so-called carcinoid syndrome consist of flushing, diarrhea, right-sided valvular heart lesions, and bronchoconstriction. All of these symptoms are at least partly caused by serotonin. The carcinoid syndrome is usually caused by midgut tumors, as foregut and hindgut neoplasms produce far lesser amounts of serotonin. Because midgut tumors drain into the portal circulation, which passes into the liver, undergoing extensive hepatic (first-pass) serotonin degradation, symptoms do not usually occur until liver or other distant metastases have developed, producing serotonin that bypasses the hepatic degradation.
Serotonin production by disseminated carcinoid tumors can sometimes be so substantial that body tryptophan stores become depleted and clinical tryptophan deficiency, resembling pellagra (triad of diarrhea, dementia, and dermatitis), develops.
Diagnosis of carcinoid tumors with symptoms suggestive of carcinoid syndrome rests on measurements of circulating and urine serotonin, urine 5-HIAA (HIAA/9248 5-Hydroxyindoleacetic Acid [5-HIAA], Urine), and serum chromogranin A (CGAK/34641 Chromogranin A, Serum), a peptide that is cosecreted alongside specific hormones by neuroectodermal cells. Urine serotonin is, in most circumstances, the least likely marker to be elevated (see Interpretation).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =210 mcg/24 hours
Reference values apply to all ages.
It is usually impossible to diagnose asymptomatic, small carcinoid tumors by measurement of serum or urine serotonin, urine 5-HIAA, or serum chromogranin A. By contrast, 1 or more of these markers are elevated in most patients with more advanced and symptomatic tumors, usually to levels several times the upper limit of the reference interval.
In patients with advanced and symptomatic tumors the following patterns of tumor marker elevations are observed:
- Serum or whole blood serotonin is elevated in nearly all patients with midgut tumors, but only in approximately 50% of those with foregut carcinoids, and in no more than 20% of individuals with hindgut tumors, because foregut and hindgut tumors often have low or absent 5-HTP decarboxylase activity and, therefore, may produce little, if any, serotonin.
- Urine 5-HIAA is elevated in almost all carcinoid-syndrome patients with midgut tumors, in about 30% of individuals with foregut carcinoids, but almost never in hindgut tumors.
- Serum chromogranin A measurements are particularly suited for diagnosing hindgut tumors, being elevated in nearly all cases, even though serotonin and 5-HIAA are often normal. Chromogranin A is also elevated in 80% to 90% of patients with symptomatic foregut and midgut tumors.
- Urine serotonin is in most circumstances the least likely marker to be elevated. The exception is tumors (usually foregut tumors) that produce predominately 5-HTP, rather than serotonin, and also secrete little, if any, chromogranin A. In this case, circulating chromogranin A, circulating serotonin levels, and urine 5-HIAA levels would not be elevated. However, the kidneys can convert 5-HTP to serotonin, leading to high urine serotonin levels.
Urine serotonin measurements are not commonly employed in carcinoid tumor follow-up. The exceptions are patients with tumors that almost exclusively secrete 5-HTP, as summarized above. In these individuals, urine serotonin is the tumor marker of choice to monitor disease progression.
In all other patients, disease progression is monitored best using urinary 5-HIAA and serum chromogranin A measurements. These markers are usually proportional to the patient's tumor burden over a wide range of tumor extent and tumor secretory activity.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Serotonin- or tryptophan-rich foods (avocados, bananas, plums, walnuts, pineapple, eggplant, plantain, tomatoes, hickory nuts, kiwi, dates, grapefruit, cantaloupe, or honeydew melon) will elevate urinary serotonin and urinary 5-HIAA levels markedly. Serum and blood serotonin and chromogranin A levels are not significantly affected by diet.
Medications that may elevate urine and serum serotonin concentrations include lithium, MAO-inhibitors, methyldopa, morphine, and reserpine. Selective serotonin reuptake inhibitors (eg, PROZAC) can lead to depletion of platelet serotonin levels and result in false-negative urine, serum, and blood serotonin tests. The effects of drugs are more marked on urine serotonin and 5-HIAA levels than on serum serotonin levels.
Heavy nicotine consumption, in particular heavy smoking, can result in false elevations of urinary serotonin levels as measured with this assay. This is due to about 1% measurement cross-reactivity of the major nicotine metabolite cotinine with serotonin. While this has no significant impact on serum or whole blood serotonin, the renal elimination of cotinine means that this metabolite is highly concentrated in urine, resulting in potential elevations in urine serotonin of 10 mcg/24 hours to 80 mcg/24 hours above the true urine serotonin level.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Kema IP, Schellings AM, Meibotg G, et al: Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites. Clin Chem 1992;38(9):1730-1736
2. Kema IP, de Vries EG, Muskiet FA: Clinical chemistry of serotonin and metabolites. J Chromatogr 2000;747(1-2):33-48
3. Meijer WG, Kema IP, Volmer M, et al: Discriminating capacity of indole markers in the diagnosis of carcinoid tumors. Clin Chem 2000;46(10):1588-1596
4. Ganim RB, Norton JA: Recent advances in carcinoid pathogenesis, diagnosis and management. Surg Oncol 2000;9(4):173-179
5. Carling RS, Degg TS, Allen KR, et al: Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem 2002;39(Pt 6):577-582
Method Description Describes how the test is performed and provides a method-specific reference
Serotonin is removed from urine using reversed-phase solid-phase extraction (SPE). Separation is completed using a Bond Elut C18 SPE cartridge, and is eluted with 40% acetonitrile /1mM ammonium acetate/0.1% formic acid. The eluate is analyzed using liquid chromatography/tandem mass spectrometry (LC-MS/MS) and quantified using a stable isotope-labeled internal standard, d(4)-serotonin.(Carling RS, Degg TS, Allen KR, et al: Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem 2002;39:577-582)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday, Friday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|26603||Serotonin, 24 Hr, U||18253-5|