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92

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

about 10% of midgut carcinoids pro-

duce enough serotonin to cause symp-

toms. Levels of over 25 mg/24 hr (131

umol/day) may indicate large carcinoid

tumors of the duodenum, ileum, biliary

tree or pancreas.

Levels of 7-25 mg/24 hr have been

associated with Celiac disease, tropical

sprue, Cystic fibrosis, foregut carcinoid

tumors, midgut carcinoid tumors, carci-

noma of the bronchus, Whipple disease

and ovarian carcinoid tumours. Foregut

carcinoid tumors may arise from the re-

spiratory tract, stomach, pancreas, or du-

odenum. Midgut carcinoid tumors may

arise from the within jejunum, ileum,

or appendix. Diagnosis of carcinoid tu-

mor requires the evaluation of multiple

biomarkers:

serotonin

urine serotonin

urine 5-HIAA

serum chromogranin A

Urine and plasma levels of 5-HIAA

may vary with the inclusion of foods

rich in serotonin or the use of medica-

tions that increase serotonin levels.

Foods, including avocados, bananas,

pineapples, plums, walnuts, tomatoes,

kiwi fruit, and eggplant may interfere

with 5-HIAA testing and should be

avoided for 3 days prior to and during

urine collection. Medications that may

increase 5-HIAA include acetamino-

phen, caffeine, ephedrine, diazepam

(Valium), nicotine, glyceryl guaiacolate

(guaifenisin), and phenobarbital. 5-HT

receptor antagonists may also elevate

5-HIAA levels.

Synthesis and Metabolism:

5-HIAA

Tryptophan

Tryptamine

5-HTP

Serotonin

MAO-A/B

TPH2

(brain)

AADC

MAO-A

ALDH

AADC

TPH1

(bodypinealgland)

Serotonin is synthesized from the

amino acid L-tryptophan in presynaptic

neurons. The enzyme tryptophan hy-

droxylase (TPH) produces 5-hydroxy-

tryptophan (5-HTP) which is converted

to serotonin by 5-HTP decarboxylase.

Once synthesized, serotonin is either

stored in neuron vesicles or metabolized

by monoamine oxidase A (MAO-A) into

5-HIAA. 5-HIAA levels represent about

1% of the tryptophan metabolized in

the body. Low levels of tryptophan

may result in low levels of serotonin

and 5-HIAA. Most peripheral serotonin

production occurs in the gastrointes-

tinal (GI) enterochromaffin cells. The

gastrointestinal tract produces about

80% of the body’s serotonin. The com-

plex interaction of the microbiome, the

immune system and the mucosa of the

intestine all have an influence on sero-

tonin synthesis, release, and degradation.

Serotonin released into the synapse is

taken back up into presynaptic neurons

by the serotonin transporter (SERT).

There may be multiple forms of SERT

(isoforms) in the body and nervous sys-