5-Hydroxyindoleacetic acid

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Contents

5-Hydroxyindoleacetic acid
5-Hydroxyindolessigsaure (5-HIAA).svg
Names
Preferred IUPAC name
(5-Hydroxy-1H-indol-3-yl)acetic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.179 OOjs UI icon edit-ltr-progressive.svg
KEGG
MeSH Hydroxyindoleacetic+Acid
PubChem CID
UNII
  • InChI=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) Yes check.svgY
    Key: DUUGKQCEGZLZNO-UHFFFAOYSA-N Yes check.svgY
  • 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)
    Key: DUUGKQCEGZLZNO-UHFFFAOYAY
  • c1cc2c(cc1O)c(c[nH]2)CC(=O)O
Properties
C10H9NO3
Molar mass 191.186 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite of serotonin. The metabolic intermediate 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 [1] combined with an acidic additive to maintain pH below 3. Certain foods like pineapple, kiwi, banana, walnuts and drugs such as acetaminophen, nicotine or caffeine are known to interfere with the measurement. [2] [3] [1] 5-HIAA levels can vary depending on other complications, including tumors, 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 (Kultschitzsky) cells of the small intestine, which release large amounts of serotonin. Values greater than 25 mg per 24 hours (higher if the patient has malabsorption) are strong evidence for carcinoid. The normal range is 2 to 6 mg per 24 hours. [4]

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. [5]

Elevated serotonin (hyperserotonemia) is one of the most common biological findings in autism [6] 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.

  1. 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. [7]
  2. 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.
  3. 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.
  4. 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. [8]

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. [8]

Related Research Articles

<span class="mw-page-title-main">Serotonin</span> Monoamine neurotransmitter

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex, touching on diverse functions including mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction.

<span class="mw-page-title-main">Tryptophan</span> Chemical compound

Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3 (niacin). It is encoded by the codon UGG.

<span class="mw-page-title-main">Uremia</span> Excess urea in the blood due to kidney dysfunction

Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure. It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">5-Hydroxytryptophan</span> Chemical compound

5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes a physiologically inappropriate increase in solute-free water being reabsorbed by the tubules of the kidney to the venous circulation leading to hypotonic hyponatremia.

Cerebral salt-wasting syndrome (CSWS), also written cerebral salt wasting syndrome, is a rare endocrine condition featuring a low blood sodium concentration and dehydration in response to injury (trauma) or the presence of tumors in or surrounding the brain. In this condition, the kidney is functioning normally but excreting excessive sodium. The condition was initially described in 1950. Its cause and management remain controversial. In the current literature across several fields, including neurology, neurosurgery, nephrology, and critical care medicine, there is controversy over whether CSWS is a distinct condition, or a special form of syndrome of inappropriate antidiuretic hormone secretion (SIADH).

<span class="mw-page-title-main">Gitelman syndrome</span> Genetic kidney disorder

Gitelman syndrome (GS) is an autosomal recessive kidney tubule disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. It is the most frequent hereditary salt-losing tubulopathy. Gitelman syndrome is caused by disease-causing variants on both alleles of the SLC12A3 gene. The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter, which can be found in the distal convoluted tubule of the kidney.

<span class="mw-page-title-main">Enterochromaffin cell</span> Cell type

Enterochromaffin (EC) cells are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal regulation, particularly intestinal motility and secretion. They were discovered by Nikolai Kulchitsky.

<span class="mw-page-title-main">Carcinoid</span> Slow-growing type of neuroendocrine tumor

A carcinoid is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut are associated with carcinoid syndrome.

<span class="mw-page-title-main">Hartnup disease</span> Metabolic disorder

Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids. Niacin is a precursor to nicotinamide, a necessary component of NAD+.

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors. The syndrome is caused by neuroendocrine tumors most often found in the gut releasing biologically active substances into the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction.

HIAA may refer to:

<span class="mw-page-title-main">Neuroendocrine tumor</span> Tumors of the endocrine and nervous systems

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body.

<span class="mw-page-title-main">Vanillylmandelic acid</span> Chemical compound

Vanillylmandelic acid (VMA) is a chemical intermediate in the synthesis of artificial vanilla flavorings and is an end-stage metabolite of the catecholamines. It is produced via intermediary metabolites.

<span class="mw-page-title-main">Phenylacetylglutamine</span> Chemical compound

Phenylacetylglutamine is a product formed by the conjugation of phenylacetate and glutamine. It is a common metabolite that occurs naturally in human urine.

<span class="mw-page-title-main">Sarpogrelate</span> Chemical compound

Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. It blocks serotonin-induced platelet aggregation, and has applications in the treatment of many diseases including diabetes mellitus, Buerger's disease, Raynaud's disease, coronary artery disease, angina pectoris, and atherosclerosis.

<span class="mw-page-title-main">Urine test strip</span> Diagnostic tool used in urinalysis

A urine test strip or dipstick is a basic diagnostic tool used to determine pathological changes in a patient's urine in standard urinalysis.

<span class="mw-page-title-main">Distal renal tubular acidosis</span> Medical condition

Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the distal tubule and cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes. It leads to relatively alkaline urine, due to the kidney's inability to acidify the urine to a pH of less than 5.3.

Intestinal metabolic bromhidrosis syndrome (IMBS) is a disorder, that is characterized by bromhidrosis and halitosis symptoms that are caused by odorous intestinal metabolites passing through the intestinal wall and by the liver to be excreted by skin glands and the lung gas exchange.

References

  1. 1 2 Burks ML, Bao S (2016-06-01). "The 24-Hour Urinary 5-HIAA: A Simple Test With a Common Pitfall". AACE Clinical Case Reports. 2 (3): e186–e188. doi: 10.4158/EP15794CR . ISSN   2376-0605.
  2. Kema IP, Schellings AM, Meiborg G, Hoppenbrouwers CJ, Muskiet FA (September 1992). "Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites". Clin Chem. 38 (9): 1730–6. doi: 10.1093/clinchem/38.9.1730 . PMID   1382000.
  3. Feldman JM, Lee EM (October 1985). "Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid". Am J Clin Nutr. 42 (4): 639–43. doi: 10.1093/ajcn/42.4.639 . PMID   2413754.
  4. MedlinePlus Encyclopedia : 5-HIAA
  5. Thomas Bronisch: Der Suizid: Ursachen Warnsignale Prävention. 5. Auflage, C.H.Beck, München 2007, ISBN   978-3-406-55967-9, S. 63–65 (German).
  6. Burgess NK, Sweeten TL, McMahon WM, Fujinami RS (2006). "Hyperserotoninemia and altered immunity in autism". Journal of Autism and Developmental Disorders. 36 (5): 697–704. doi:10.1007/s10803-006-0100-7. PMID   16614791. S2CID   26442860.
  7. "Carcinoid Tumors and Syndrome". The Lecturio Medical Concept Library. Retrieved 6 July 2021.
  8. 1 2 Deacon AC (May 1994). "The measurement of 5-hydroxyindoleacetic acid in urine". Ann Clin Biochem. 31 (Pt 3) (3): 215–32. doi:10.1177/000456329403100302. PMID   7520678. S2CID   39995403.

Further reading