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Functional Assessment of Urinary Neuro-biogenic Amines—A COMPREHENSIVE GUIDE 


5-hydroxyindoleacetic acid


5-hydroxyindoleacetic acid (5-

HIAA) is a metabolite of serotonin.

Clinically, urinary 5-HIAA is an indica-

tor of serotonin synthesis and metabo-

lism. Levels of serotonin and 5-HIAA

may be affected by a variety of factors.

Ninety-five percent of the body’s sero-

tonin is found in the gut.



levels (2 mg/24 hr) of uri-

nary 5-HIAA have been associated with

depression, Hartnup disease, mastocy-

tosis, phenylketonuria, renal disease or

small bowel resection.Low levels of tryp-

tophan or serotonin may result in low

levels of 5-HIAA. Medications that may

decrease 5-HIAA include aspirin, ethyl

alcohol, imipramine, levodopa, MAO in-

hibitors, heparin, isoniazid, methyldopa,

and tricyclic antidepressants.


5-HIAA has been associat-

ed with Celiac disease and chronic re-

nal insufficiency. A study demonstrated

elevated plasma levels of serotonin, its

metabolite 5-hydroxyindolacetic acid

(5-HIAA), and urine albumin in and

Asian population of men with Type

II diabetes. Exogenous estrogens have

been shown to elevate both serotonin

and 5-HIAA levels in post-menopaus-

al women. Serotonin is converted into

melatonin by the enzyme arylalkyl-

amine N-acetyltransferase; deficient

function of this enzyme may result in el-

evated serotonin and 5-HIAA levels and

low melatonin levels. Deficient function

of the serotonin transporter (SERT) may

prevent normal reuptake of serotonin by

pre-synaptic neurons, and result in ele-

vated serotonin and 5-HIAA levels.

Serotonin Syndrome is an excess of

serotonin due to a sudden change in se-

rotonin re-uptake function. The change

in serotonin reuptake is usually due to a

new medication, such as a serotonin re-

uptake inhibitor (SSRI) or a monoamine

oxidase inhibitor (MAOI). Symptoms

of serotonin excess are wide-ranging.

A triad of symptoms including altered

mental status, neuromuscular hyperac-

tivity or hyper-reflexia, and autonomic

instability, is suspicious for serotonin ex-

cess. Symptoms of Serotonin Syndrome





Dilated pupils


Changes in blood pressure,


Nausea or vomiting


Rapid heart rate


Loss of muscle coordination

Twitching muscles

Shivering and goose bumps

Heavy sweating

The main disease that may be as-

sociated with measurable increases in

5-HIAA is carcinoid tumors arising from

GI enterochromaffin cells. The enzyme

5-HTP decarboxylase, which converts

the intermediate 5-hydroxytryptophan

(5-HTP) to serotonin, is present in mid-

gut tumors. About 70% of cases are mid-

gut carcinoids (tumors are found within

the jejunum, ileum, or appendix). Only