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# A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Serotonin, Serum (SER)
Test Code: SEROTSO
Synonyms/Keywords
​Ref Lab Code: 84395
Useful For
In conjunction with, or as an alternative to, with 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 measurements are first-line tests) in the follow-up of patients with known or treated carcinoid tumors.​
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Red Top Tube (RTT) ​Serum Separator Tube (SST) ​2.5 mL ​1.1 mL
Collection Processing Instructions
Spin down as soon as blood has clotted. Submit specimen in plastic vial.
Additional Information: Medications that may affect serotonin concentrations include lithium, MAO inhibitors, methyldopa, morphine, and reserpine.​
Specimen Stability Information
Specimen Type Temperature Time
​Serum ​​Refrigerate (preferred) ​21 days
Room Temperature ​4 days
​Frozen ​90 days
Rejection Criteria
Hemolysis
Mild OK; Gross OK
​Lipemia
Mild OK; Gross OK
​Icterus
Mild OK; Gross OK
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Medical Laboratories ​Monday, Wednesday, Friday ​2 days
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)​
Reference Lab
Test Information
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% 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 arcinoids, 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, Urine), and serum chromogranin A (CGAK/34641Chromogranin A, Serum), a peptide that is cosecreted alongside specific hormones by neuroectodermal cells.
Reference Range Information
Performing Location Reference Range
​Mayo Medical Laboratories ​<=230 ng/mL
Interpretation
Metastasizing midgut carcinoid tumors usually produce blood or serum 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-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-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 80-90% 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.
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​84260
Synonyms/Keywords
​Ref Lab Code: 84395
Ordering Applications
Ordering Application Description
​Centricity ​Serotonin, Serum
​Cerner ​Serotonin Level (84395)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Red Top Tube (RTT) ​Serum Separator Tube (SST) ​2.5 mL ​1.1 mL
Collection Processing Instructions
Spin down as soon as blood has clotted. Submit specimen in plastic vial.
Additional Information: Medications that may affect serotonin concentrations include lithium, MAO inhibitors, methyldopa, morphine, and reserpine.​
Specimen Stability Information
Specimen Type Temperature Time
​Serum ​​Refrigerate (preferred) ​21 days
Room Temperature ​4 days
​Frozen ​90 days
Rejection Criteria
Hemolysis
Mild OK; Gross OK
​Lipemia
Mild OK; Gross OK
​Icterus
Mild OK; Gross OK
Useful For
In conjunction with, or as an alternative to, with 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 measurements are first-line tests) in the follow-up of patients with known or treated carcinoid tumors.​
Test Information
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% 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 arcinoids, 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, Urine), and serum chromogranin A (CGAK/34641Chromogranin A, Serum), a peptide that is cosecreted alongside specific hormones by neuroectodermal cells.
Reference Range Information
Performing Location Reference Range
​Mayo Medical Laboratories ​<=230 ng/mL
Interpretation
Metastasizing midgut carcinoid tumors usually produce blood or serum 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-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-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 80-90% 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.
For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Medical Laboratories ​Monday, Wednesday, Friday ​2 days
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​84260
For most current information refer to the Marshfield Laboratory online reference manual.