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

85

of serotonin excess are wide-ranging.

A triad of symptoms including altered

mental status, neuromuscular hyperac-

tivity or hyperreflexia, and autonomic

instability, is suspicious for serotonin ex-

cess. Symptoms of Serotonin Syndrome

include:

Confusion

Agitation

Restlessness

Dilated pupils

Headache

Changes in blood pressure,

temperature

Nausea or vomiting

Diarrhea

Rapid heart rate

Tremor

Loss of muscle coordination

Twitching muscles

Shivering and goose bumps

Heavy sweating

The main diseases that may be asso-

ciated with measurable increases in se-

rotonin are neuroectodermal tumors, in

particular, carcinoid tumors arising from

GI enterochromaffin cells. The enzyme

5-HTP decarboxylase, which converts

the intermediate 5-HTP to serotonin, is

present in midgut tumors. About 70%

of cases are midgut carcinoids (tumors

are found within the jejunum, ileum, or

appendix). Only about 10% of midgut

carcinoids produce enough serotonin to

cause symptoms. Diagnosis of carcinoid

tumor requires evaluation of multiple

biomarkers:

plasma serotonin

urine serotonin

urine 5-HIAA (HIAA /

5-Hydroxyindoleacetic Acid)

serum chromogranin A

Urine serotonin is the least like-

ly marker to be elevated, and is not, in

isolation, considered diagnostic for car-

cinoid tumors. Urine and plasma levels

of serotonin and 5-HIAA may vary with

the inclusion of foods rich in serotonin

or the use of medications that increase

serotonin levels. Foods including avoca-

dos, bananas, pineapples, plums, walnuts,

tomatoes, kiwi fruit, and eggplant may

interfere with serotonin and 5-HIAA

testing and should be avoided for 3 days

prior to and during urine collection.

Medications that may increase 5-HIAA

include acetaminophen, caffeine, ephed-

rine, diazepam (Valium), nicotine, glyc-

eryl guaiacolate (guaifenisin), and phe-

nobarbital. 5-HT receptor antagonists

may also elevate serotonin and 5-HIAA

levels.

Serotonin and Migraine

Research continues into the origin of

migraine headaches. Evidence indicates

that dysregulation of serotonin synthe-

sis and signaling in certain areas of the

brain may contribute to the causation

of migraine headaches. The current un-

derstanding of the relationship between

serotonin and migraine headaches

includes:

Migraineurs are predominantly

female

There are gender differences

in serotonin transporters in

the midbrain and in peripheral

platelet cells