5-Hydroxyindoleacetic acid

Last updated
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. In chemical analysis of urine samples, 5-HIAA is used to determine serotonin levels in the body.

Contents

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. This multifacetedness has led to its study being described as "like the fable of the blind men and the elephant".

Albuminuria is a pathological condition wherein the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein ; in healthy people, only trace amounts of it are present in urine, whereas larger amounts occur in the urine of patients with kidney disease. For a number of reasons, clinical terminology is changing to focus on albuminuria more than proteinuria.

<span class="mw-page-title-main">Uremia</span> Type of kidney disease, urea in the blood

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.

<span class="mw-page-title-main">Hyperuricemia</span> Medical condition

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

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.

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

Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier.

The Schilling test was a medical investigation used for patients with vitamin B12 (cobalamin) deficiency. The purpose of the test was to determine how well a patient is able to absorb B12 from their intestinal tract. The test is now considered obsolete and is rarely performed, and is no longer available at many medical centers. It is named for Robert F. Schilling.

<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.

<span class="mw-page-title-main">Dubin–Johnson syndrome</span> Genetic liver disease

Dubin–Johnson syndrome is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.

HIAA may refer to:

<span class="mw-page-title-main">Neuroendocrine tumor</span> Medical condition

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">Guanidinoacetate methyltransferase deficiency</span> Medical condition

Guanidinoacetate methyltransferase deficiency is an autosomal recessive cerebral creatine deficiency that primarily affects the nervous system and muscles. It is the first described disorder of creatine metabolism, and results from deficient activity of guanidinoacetate methyltransferase, an enzyme involved in the synthesis of creatine. Clinically, affected individuals often present with hypotonia, seizures and developmental delay. Diagnosis can be suspected on clinical findings, and confirmed by specific biochemical tests, brain magnetic resonance spectroscopy, or genetic testing. Biallelic pathogenic variants in GAMT are the underlying cause of the disorder. After GAMT deficiency is diagnosed, it can be treated by dietary adjustments, including supplementation with creatine. Treatment is highly effective if started early in life. If treatment is started late, it cannot reverse brain damage which has already taken place.

<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.

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