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Serotonin, Whole Blood

CPT: 84260
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Synonyms

  • 5-HT, Whole Blood
  • 5-Hydroxytryptamine, Blood

Expected Turnaround Time

4 - 6 days


Related Information


Related Documents


Specimen Requirements


Specimen

Whole blood, frozen


Volume

10 mL EDTA/ascorbic acid mixture (see Collection below)


Container

Lavender-top (EDTA) tube and transport tube (LabCorp N° 33314) containing 75 mg ascorbic acid


Collection

Sample collection practices that prevent blood clotting and oxidation of serotonin are imperative. Collect three tubes (4 mL each) whole blood. Invert tubes at least ten times to ensure thorough distribution of EDTA. Immediately transfer 10 mL whole blood to transport tube containing 75 mg ascorbic acid. Thoroughly mix by inverting whole blood/ascorbic acid mixture another ten times. Freeze transport tube and send entire collection to the laboratory. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.


Storage Instructions

Freeze. Please note that stability claims reflect stability of properly prepared whole blood with ascorbic acid preservative.


Stability Requirements

Temperature

Period

Room temperature

4 hours

Refrigerated

24 hours

Frozen

16 days

Freeze/thaw cycles

Stable x2


Patient Preparation

Monoamine oxidase inhibitor drugs should be discontinued for at least one week prior to sampling since they tend to increase the level of serotonin.


Causes for Rejection

Receipt of non-frozen specimen; specimen stored without preservative


Test Details


Use

Serotonin measurement is used in conjunction with urinary 5-hydroxyindoleacetic acid (5-HIAA) and/or serum chromogranin A in the diagnosis of carcinoid syndrome.


Limitations

The majority of gastroenteropancreatic neuroendocrine, carcinoid tumors do not produce elevated whole blood or serum serotonin levels. In most cases, 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A are superior tests for the assessment of carcinoid syndrome.1-4 In rare instances, a deficiency of aromatic amino acids decarboxylase in carcinoid tumor cell limits the conversion of 5-HTP into serotonin.17

Several medications (lithium, monoamine oxidase inhibitors, methyldopa, morphine, and reserpine) can produce elevation in serotonin concentration. Selective serotonin reuptake inhibitors can cause a reduction in serum and whole blood serotonin levels. Tryptophan-rich food (avocados, bananas, plums, walnuts, pineapple, eggplant, plantain, tomatoes, hickory nuts, kiwi, dates, grapefruit, cantaloupe, and honeydew melon) do not contribute to serum or blood serotonin measurements.12,13

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)


Reference Interval

• Pediatric:1 0-18 years: 113−431 ng/mL

• Adults: >18 years: 11−204 ng/mL


Additional Information

Carcinoid tumors are slow-growing neuroendocrine tumors derived from enterochromaffin cells that are widely distributed throughout the body.1-4 Approximately 65 percent of carcinoid tumors are found in the gastrointestinal tract from the foregut, midgut, and hindgut, and another 25 percent originate in the bronchopulmonary tract.3,4 The primary site for one in 10 cases remain undetermined.3 About a quarter of cases present with distant metastases, half of which have unknown primary tumor location.3

Carcinoid tumors secrete a variety of peptides and small molecules.1,4-6 Midgut carcinoid tumors frequently produce serotonin. Serotonin secreting carcinoids from other locations are less common. Serotonin (5-hydroxytryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin secretion in the gut causes an increase in gastrointestinal blood flow, motility, and fluid secretion. In healthy individuals, the great majority of serotonin made by the gut is converted by the liver and lungs to 5-hydroxyindoleacetic acid (5-HIAA) via first pass metabolism prior to entering the general circulation. Almost the entirety of the small amount of serotonin that survives the first pass metabolism is taken up by platelets. Platelets store serotonin until it is released as part of the clotting process to promote platelet aggregation.

Serotonin secreting carcinoid tumors are relatively slow growing, and in most cases, asymptomatic.1,4,6 The local, paracrine effect of increased serotonin on the gut intestine can cause diarrhea, malabsorption and tumor mass producing discomfort.4,7 Since most serotonin produced by carcinoid tumors is metabolized prior to reaching the circulation, the metabolic product, 5-HIAA, in urine is usually the most important marker for carcinoid tumors.4

In cases where a larger amount of serotonin reaches the systemic circulation (advanced disease with liver metastases bypassing first pass metabolism), patients can present with a constellation of symptoms referred to as the carcinoid syndrome. The carcinoid syndrome can also occur in the absence of liver metastases in cases where tumor pathology causes direct venous drainage of serotonin bypassing first pass liver metabolism.5,8 Carcinoid syndrome is relatively rare and is most commonly associated with midgut carcinoid tumors.2,4 Carcinoid syndrome occurs in 20% of cases of well-differentiated endocrine tumors of the jejunum or ileum.5,8 Carcinoid syndrome occurs less often with neuroendocrine tumors of other origins and is very rare in association with rectal NETs.5,8

Carcinoid syndrome is characterized by one or more symptoms including diarrhea, dry flushing without sweating with or without palpitations, and intermittent abdominal pain.5 Some patients also experience lacrimation and rhinorrhea. 5,8 Advance or long-standing carcinoid syndrome can lead to carcinoid heart disease involving the tricuspid and pulmonary valves of the heart.7,9 Other cardiovascular complications include bowel ischemia and hypertension.7 Approximately one in five patients with carcinoid syndrome sent with heart disease at diagnosis.5,8 Carcinoid tumors are classified similarly whether they produce symptoms of the carcinoid syndrome or not.10

The primary laboratory tests for the diagnosis and assessment of carcinoid tumors are serum chromogranin A and, in the case of tumors presenting with carcinoid syndrome, urinary 5-HIAA. Direct measurement of serotonin is considered a secondary test for this condition.14-16 Whole blood serotonin is measured because most circulating serotonin is contained in platelets and whole blood levels correlated with platelet levels. Alternatively, serum serotonin levels can be measured because the process of blood clotting causes the release of all platelet serotonin in to the serum.

In healthy individuals, approximately 99 percent of dietary tryptophan is metabolized by the oxidative pathway into nicotinic acid (vitamin B3).4 In carcinoid tumors, excessive conversion of tryptophan to serotonin can cause result in vitamin B3 deficiency referred to as pellagra, a condition that is characterized by the triad of symptoms; diarrhea, dementia, and dermatitis.11


Footnotes

1. Aggarwal G, Obideen K, Wehbi M. Carcinoid tumors: What should increase our suspicion? Cleve Clin J Med. 2008 Dec;75(12):849-855.19088003
2. Robertson RG, Geiger WJ, Davis NB. Carcinoid tumors. Am Fam Physician. 2006 Aug 1;74(3):429-434.16913162
3. Modlin IM, Lye KD, Kidd M. A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem? Am H Gastroenterol. 2004 Jan;99(1):23-32.14687136
4. Zueterhorst JM, Taal BG. Metastatic carcinoid tumors: a clinical review. Oncologist. 2005 Feb;10(2):123-131.15709214
5. Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012 Jan;61(1):6-32.22052063
6. Ghevariya V, Malieckal A, Ghevariya N, Mazumder M, Arand S. Carcinoid tumors of the gastrointestinal tract. South Med J. 2009 Oct;102(10):1032-1040.19738517
7. van der Horst-Schrivers AN, Wymenga AN, Links TP, Willemse PH, Kema IP, deVries EG. Complications of midgut carcinoid tumors and carcinoid syndrome. Neuroendocrinology. 2004;80 Suppl 1:28-32.15477713
8. Pape UF, Perren A, Niederle B, et al. ENETS Consensus Guidelines for the management if patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomase. Neuroendocrinology. 2012;95(2):135-156.22262080
9. Robiolio PA, Rigolin VH, Wilson JS, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995 Aug 15;92(4):790-795.7641358
10. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors. a review of nomenclature, grading, and stagging systems. Pancreas. 2010 Aug;39(6):707-712.20664470
11. Castiello RJ, Lynch PJ. Pellagra and the carcinoid syndrome. Arch Dermatol. 1972 Apr;105(4):574-577.4259595
12. Kema IP, Schellings AM, Meiborg G, Hoppenbrouwers CJ, Muskiet FA. Influence of a serotonin-and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites. Clin Chem. 1992 Sep;38:1730-1736.1382000
13. Kema IP, de Vires EG, Muskiet FA. Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Appl. 2000 Sep 29;747(1-2):33-48.11103898
14. Pussard E, Guigueno N, Adam O, Giudicelli JF. Validation of HPLC-amperometric detection to measure serotonin in plasma, platelets, whole blood, and urine. Clin Chem. 1996 Jul;42(7): 1086-1091.8674193
15. Carling RS, Degg TJ, Allen KR, Bax NDS, Barth JH. Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole- acetic acid in the diagnosis of carcinoid disease. Ann Clin Biochem. 2002 Nov;39(Pt 6):577-582.12564839
16. Allen KR, Degg TJ, Anthoney DA, Fitzroy-Smith D. Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: three case examples. Ann Clin Biochem. 2007 May;44(Pt 3):300-307.17456301
17. Feldman JM. Serotonin metabolism in patients with carcinoid tumors; incidence of 5-hydroxytryptohan-secreting tumors. Gastroenterology. 1978 Dec;75(6):1109-1114.309417

References

Kocha W, Maroun J, Kennecke H, et al. Consensus recommendations for the diagnosis and management of well- differentiated gastroentererohepatic neuroendocrine tumours: a revised statement from a Canadian National Expert Group. Curr Oncol. 2010 Jun;17(3):49-64.20567626
Meijer W, Kema I, Volmer M, Willemse PH, de Vries EG. Discriminating capacity of indole markers in the diagnosis of carcinoid tumors. Clin Chem. 2000 Oct;46(10):1588-1596.11017936

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
120089 Serotonin, Whole Blood 2939-7 120089 Serotonin, Whole Blood ng/mL 2939-7

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