View source for 5-Hydroxyindoleacetic acid

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{{chembox
| Watchedfields = changed
| verifiedrevid = 477224591
| ImageFile = 5-Hydroxyindolessigsäure (5-HIAA).svg
| ImageSize = 200px
| PIN = (5-Hydroxy-1''H''-indol-3-yl)acetic acid
| OtherNames = 
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1760
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C05635
| InChI = 1/C10H9NO3/c12-7-1-2-9-8(4-7)6(5-11-9)3-10(13)14/h1-2,4-5,11-12H,3H2,(H,13,14)
| InChIKey = DUUGKQCEGZLZNO-UHFFFAOYAY
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H9NO3/c12-7-1-2-9-8(4-7)6(5-11-9)3-10(13)14/h1-2,4-5,11-12H,3H2,(H,13,14)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DUUGKQCEGZLZNO-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 54-16-0
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = YHC763JY1P
| PubChem = 1826
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 395915
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 27823
| SMILES = c1cc2c(cc1O)c(c[nH]2)CC(=O)O
| MeSHName = Hydroxyindoleacetic+Acid
  }}
|Section2={{Chembox Properties
| C=10 | H=9 | N=1 | O=3 
| Appearance =
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|Section3={{Chembox Hazards
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'''5-Hydroxyindoleacetic acid''' ('''5-HIAA''') is the main [[metabolite]] of [[serotonin]]. The [[metabolic intermediate]] [[5-Hydroxyindoleacetaldehyde|5-hydroxyindoleacetaldehyde]] (5-HIAL) is formed from serotonin by [[monoamine oxidase]] (MAO) and then 5-HIAA is formed from 5-HIAL via [[aldehyde dehydrogenase]] (ALDH). In [[chemical analysis]] of [[urine]] samples, 5-HIAA is used to determine serotonin levels in the body.

== Clinical significance ==
5-HIAA is tested by 24-hour urine samples<ref name = "Burks_2016">{{cite journal |vauthors = Burks ML, Bao S |date=2016-06-01 |title=The 24-Hour Urinary 5-HIAA: A Simple Test With a Common Pitfall |url=https://www.aaceclinicalcasereports.com/article/S2376-0605(20)30585-X/abstract |journal=AACE Clinical Case Reports |language=English |volume=2 |issue=3 |pages=e186–e188 |doi=10.4158/EP15794CR |issn=2376-0605|doi-access=free }}</ref> combined with an acidic additive to maintain pH below 3. Certain foods like [[pineapple]], [[Kiwifruit|kiwi]], [[banana]], [[walnut]]s and drugs such as [[acetaminophen]], [[nicotine]] or [[caffeine]] are known to interfere with the measurement.<ref name="pmid1382000">{{cite journal | vauthors = Kema IP, Schellings AM, Meiborg G, Hoppenbrouwers CJ, Muskiet FA | title = Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites | journal = Clin Chem | volume = 38 | issue = 9 | pages = 1730–6 | date = September 1992 | pmid = 1382000 | doi = 10.1093/clinchem/38.9.1730 | doi-access = free }}</ref><ref name="pmid2413754">{{cite journal | vauthors = Feldman JM, Lee EM | title = Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid | journal = Am J Clin Nutr | volume = 42 | issue = 4 | pages = 639–43 | date = October 1985 | pmid = 2413754 | doi = 10.1093/ajcn/42.4.639 | doi-access = free }}</ref><ref name = "Burks_2016"/> 5-HIAA levels can vary depending on other complications, including [[tumor]]s, [[kidney]] malfunction, and small [[bowel resection]].

Since 5-HIAA is a metabolite of serotonin, testing is most frequently performed for the diagnosis of [[carcinoid]] tumors of the [[enterochromaffin cell|enterochromaffin (Kultschitzsky) cells]] of the small intestine, which release large amounts of serotonin. Values greater than 25&nbsp;mg per 24 hours (higher if the patient has [[malabsorption]]) are strong evidence for carcinoid. The normal range is 2 to 6&nbsp;mg per 24 hours.<ref>{{MedlinePlusEncyclopedia|003612|5-HIAA}}</ref>

Low levels of 5-HIAA in the [[cerebrospinal fluid]] have been associated with aggressive behavior and suicide by violent means, correlating with diminished serotonin levels.<ref>Thomas Bronisch: ''Der Suizid: Ursachen Warnsignale Prävention.'' 5. Auflage, C.H.Beck, München 2007, {{ISBN|978-3-406-55967-9}}, S.&nbsp;63–65 (German).</ref>

Elevated serotonin ([[hyperserotonemia]]) is one of the most common biological findings in [[autism]]<ref>{{cite journal | last1 = Burgess | first1 = NK | last2 = Sweeten | first2 = TL | last3 = McMahon | first3 = WM | last4 = Fujinami | first4 = RS | title = Hyperserotoninemia and altered immunity in autism. | journal = Journal of Autism and Developmental Disorders | volume = 36 | issue = 5 | pages = 697–704 | year = 2006 | pmid = 16614791 | doi = 10.1007/s10803-006-0100-7| s2cid = 26442860 }}</ref> and 5-HIAA may be elevated in patients with autistic spectrum disorders.

==Limitations==
5-HIAA may be normal with nonmetastatic carcinoid tumor and may be normal even with the carcinoid syndrome, particularly in subjects without diarrhea, because some patients with the carcinoid syndrome excrete nonhydroxylated indolic acids.
# Midgut carcinoids are most apt to produce carcinoid syndrome with 5-HIAA elevation. Patients with renal disease may have falsely low 5-HIAA levels in the urine.<ref>{{cite web |url=https://www.lecturio.com/concepts/carcinoid-tumors-and-syndrome/ | title= Carcinoid Tumors and Syndrome
| website= The Lecturio Medical Concept Library |access-date= 6 July 2021}}</ref>
# 5-HIAA is increased in untreated patients with malabsorption, who have increased urinary tryptophan metabolites. Such patients include those with celiac disease, tropical sprue, Whipple disease, stasis syndrome, and cystic fibrosis. It is increased in those with chronic intestinal obstruction.
# Poor correlation exists between 5-HIAA level and the clinical severity of the carcinoid syndrome. 3 recent studies confirm its use as a prognostic factor in this disease.
# 5-HIAA is the major urinary metabolite of serotonin, a ubiquitous bioactive amine. Serotonin, and consequently 5-HIAA, are produced in excess by most carcinoid tumors, especially those producing the carcinoid syndrome of flushing, hepatomegaly (enlarged [[liver]]), diarrhea, bronchospasm, and heart disease. Quantitation of urinary 5-HIAA is the best test for carcinoid, but scrupulous care must be taken that specimen collection and patient preparation have been correct. Carcinoid tumors may cause increased excretion of tryptophan, 5-hydroxytryptophan and histamine as well as serotonin. Serum serotonin assay may detect some carcinoids missed by 5-HIAA assay.<ref name="pmid7520678">{{cite journal | vauthors = Deacon AC | title = The measurement of 5-hydroxyindoleacetic acid in urine | journal = Ann Clin Biochem | volume = 31 (Pt 3) | issue = 3| pages = 215–32 | date = May 1994 | pmid = 7520678 | doi = 10.1177/000456329403100302 |s2cid= 39995403}}</ref>

The production and metabolism of serotonin, and thus 5-HIAA, is dependent upon the tissue of origin of the tumor. Tumors from midgut cells, such as ileal carcinoid usually contain and release large quantities of serotonin. These amounts may not be fully reflected in the amount of 5-HIAA in urine, because little is metabolized. Foregut tumors lack the decarboxylase enzyme necessary to convert 5-hydroxytryptophan to serotonin, resulting in minimal to no elevation in urinary 5-HIAA levels. Tumors derived from hindgut cells (rectal carcinoid) rarely produce excess serotonin or 5-HIAA. Of 75 patients with carcinoid tumors, 75% had above normal urinary 5-HIAA excretion and 64% had above normal serotonin excretion.<ref name="pmid7520678"/>

==References==
{{reflist}}

==Further reading==
* {{cite book |author1=Berk, J. Edward |author2=Bockus, Henry L. |title=Bockus gastroenterology |publisher=W.A. Saunders |location=Philadelphia |year=1985 |isbn=0-7216-1777-8 }} - Johnson HC Jr, “Urine Tests,” Volume 1, 342–7.
*Schultz AL, “5-Hydroxyindoleacetic Acid,” Methods in Clinical Chemistry, Pesce AJ and Kaplan LA, eds, St Louis, MO: Mosby-Year Book Inc, 1987, 714–20.
* {{cite book |author1=Berk, J. Edward |author2=Bockus, Henry L. |title=Bockus gastroenterology |publisher=W.A. Saunders |location=Philadelphia |year=1985 |isbn=0-7216-1777-8 }} - Warner RR, “Carcinoid Tumor,” Volume 3, 1874–6.
* {{cite journal |vauthors=Agranovich AL, Anderson GH, Manji M, Acker BD, Macdonald WC, Threlfall WJ |title=Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome |journal=J Surg Oncol |volume=47 |issue=1 |pages=45–52 |date=May 1991 |pmid=1708841 |doi= 10.1002/jso.2930470111|s2cid=30043654 }}
* {{cite journal |author=Feldman JM |title=Urinary serotonin in the diagnosis of carcinoid tumors |journal=Clin. Chem. |volume=32 |issue=5 |pages=840–4 |date=May 1986 |doi=10.1093/clinchem/32.5.840 |pmid=2421946 |url=http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=2421946 |doi-access=free |url-access=subscription }}{{Dead link|date=June 2020 |bot=InternetArchiveBot |fix-attempted=yes }}

{{Neurotransmitter metabolism intermediates}}
{{Nicotinic acetylcholine receptor modulators}}

{{DEFAULTSORT:Hydroxyindoleacetic acid, 5-}}

[[Category:Indoles]]
[[Category:Acetic acids]]
[[Category:Hydroxyarenes]]
[[Category:Nicotinic antagonists]]
[[Category:Human metabolites]]
[[Category:Hydroxy acids]]