NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
In conjunction with, or as an alternative to, 5-hydroxyindoleacetic acid (5-HIAA) or serum chromogranin A measurements as a first-line test in the diagnosis of carcinoid syndrome. This includes the differential diagnosis of isolated symptoms suggestive of carcinoid syndrome, in particular flushing.
As a second-line test (5-HIAA or serum chromogranin A measurement are first-line tests) in the follow-up of patients with known or treated carcinoid tumors.
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
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
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.
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Serotonin tube (Supply T259) containing ascorbic acid
Specimen Volume: 2.5 mL
1. Transfer 2.5 mL whole blood to serotonin tube and mix well.
Note: The amount of whole blood added to the tube is based on the amount of ascorbic acid.
2. Immediately freeze specimen.
Additional Information: Medications that may affect serotonin concentrations include lithium, MAO inhibitors, methyldopa, morphine, and reserpine.
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.
Mild OK; Gross OK
Mild OK; Gross OK
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Frozen (preferred)||90 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Serotonin (5-hydroxytryptamine; 5-HT) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). 5-HT 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 5-HT pools are isolated from each other. EC-cell production accounts for 80% of the body's 5-HT content.
Many different stimuli can release 5-HT from EC-cells. Once secreted, in concert with other gut hormones, 5-HT increases GI blood flow, motility, and fluid secretion. On first-pass through the liver, 30% to 80% of 5-HT 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 5-HT 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). 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 5-HT, 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 5-HT. The carcinoid syndrome is usually caused by midgut tumors, as foregut and hindgut neoplasms produce far lesser amounts of 5-HT. Since midgut tumors drain into the portal circulation, which passes into the liver, symptoms do not usually occur until liver or other distant metastases have developed, bypassing the extensive hepatic first-pass 5-HT 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 urinary 5-HT, urinary 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.
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 =330 ng/mL
Metastasizing midgut carcinoid tumors usually produce blood or serum 5-hydroxytryptamine (5-HT) concentrations >1,000 ng/mL. However, elevations >400 ng/mL are suggestive of carcinoid tumors as the cause of carcinoid syndrome-like symptoms. Lesser increases may be nonspecific or drug-related (see Cautions).
Only a minority of patients with carcinoid tumors will have elevated 5-HT levels. It is usually impossible to diagnose small carcinoid tumors (>95% of cases) without any symptoms suggestive of carcinoid syndrome by measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), or chromogranin A.
In patients with more advanced tumors, circulating 5-HT 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. Foregut and hindgut tumors often have low or absent 5-hydroxytryptophan (5-HTP) decarboxylase activity and, therefore, may produce little if any 5-HT. Urinary 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 5-HT and 5-HIAA are often normal. Chromogranin A is also elevated in 80% to 90% of patients with foregut and midgut tumors. Therefore, to achieve maximum sensitivity in the initial diagnosis of suspected carcinoid tumors, 5-HT in serum/blood, 5-HIAA in urine, and serum chromogranin A should all be measured. In most cases, if none of these 3 analytes is elevated, carcinoids can be excluded as a cause of symptoms suggestive of carcinoid syndrome. For some cases, additional tests, such as urinary 5-HT measurement will be required. An example would be a nonchromogranin-secreting foregut tumor that only produces 5-HTP, rather than 5-HT. In this case, circulating chromogranin, 5-HT levels, and urinary 5-HIAA levels would not be elevated. However, the kidneys can convert 5-HTP to 5-HT, leading to high urinary 5-HT levels.
Disease progression can be monitored in patients with serotonin-producing carcinoid tumors by measurement of 5-HT in blood. However, at levels above approximately 5,000 ng/mL, the serotonin storage capacity of platelets becomes limiting, and there is no longer a linear relationship between tumor burden and blood 5-HT levels. Urinary 5-HIAA and serum chromogranin A continue to increase in proportion to the tumor burden to much higher 5-HT production levels, and are therefore better suited for follow-up in patients with extensive disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Since most circulating 5-hydroxytryptamine (5-HT) is contained in platelets, the preferred specimens for measurement either include all or most of the platelets (ie, whole blood and platelet-rich plasma) or consist of serum from completely clotted specimens, a process that releases nearly all 5-HT from platelets. "Ordinary" or platelet-poor plasma specimens are not suitable.
Medications that may elevate serotonin concentrations include lithium, MAO inhibitors, methyldopa, morphine, and reserpine. The observed levels are usually <400 ng/mL. Selective serotonin reuptake inhibitors (eg, fluoxetine) can lead to depletion of platelet serotonin levels and result in false-negative serum and blood 5-HT tests. The effects of drugs are more marked on urinary 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels than on serum and blood 5-HT levels.
Serotonin- or tryptophan-rich foods (avocados, bananas, plums, walnuts, pineapple, eggplant, plantain, tomatoes, hickory nuts, kiwi, dates, grapefruit, cantaloupe, and honeydew melon) do not contribute significantly to serum or blood 5-HT measurements, but can elevate platelet-poor plasma 5-HT, urinary 5-HT, and urinary 5-HIAA levels markedly (up to 10-fold).
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;38:1730-1736
2. Kema IP, de Vries EGE, Muskiet FAJ: Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Appl 2000;747:33-48
3. Meijer W, Kema I, Volmer M, et al: Discriminating capacity of indole markers in the diagnosis of carcinoid tumors. Clin Chem 2000;46:1588-1596
4. Ganim RB, Norton JA: Recent advances in carcinoid pathogenesis, diagnosis and management. Surg Oncol 2000;9:173-179
Method Description Describes how the test is performed and provides a method-specific reference
Serotonin is extracted from the sample 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|