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Test ID SERU Serotonin, 24 Hour, Urine

Reporting Name

Serotonin, 24 Hr, U

Useful For

The diagnosis of a small subgroup of carcinoid tumors that produce predominately 5-hydroxytryptophan (5-HTP), but very little serotonin and chromogranin A

 

Follow-up of patients with known or treated carcinoid tumors that produce predominately 5-HTP, but very little serotonin and chromogranin A

Specimen Type

Urine


Specimen Required


Container/Tube: Plastic, 10-mL urine tube (T068)

Specimen Volume: 5 mL

Collection Instructions:

1. Collect urine for 24-hours.

2. Add 25 mL of 50% acetic acid as preservative at start of collection.

3. Refrigerate specimen during collection.

4. Patients should not eat avocados, bananas, butternuts, cantaloupe, dates, eggplant, grapefruit, hickory nuts, honeydew melon, kiwifruit, melon, nuts, pecans, pineapple, plantains, plums, tomatoes, or walnuts, which are high in serotonin for 48 hours before or during collection.

Additional Information:

1. 24-Hour volume is required.

2. See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens in Special Instructions for multiple collections.


Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Frozen (preferred) 14 days
  Refrigerated  7 days

Reference Values

≤210 mcg/24 hours 

Reference values apply to all ages.

Day(s) and Time(s) Performed

Monday, Wednesday, Friday; 10 a.m.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

84260

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SERU Serotonin, 24 Hr, U 18253-5

 

Result ID Test Result Name Result LOINC Value
26603 Serotonin, 24 Hr, U 18253-5
TM80 Collection Duration 13362-9
VL67 Urine Volume 3167-4

Clinical Information

Serotonin (5-hydroxytryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin production sites are the central nervous system (CNS), where it acts as a neurotransmitter, and neuroectodermal cells, chiefly gastrointestinal (GI) enterochromaffin cells (EC-cells). The CNS and peripheral serotonin pools are isolated from each other. EC-cell production accounts for 80% of the body's serotonin content.

 

Many different stimuli can release serotonin from EC-cells. Once secreted, in concert with other gut hormones, serotonin increases GI blood flow, motility, and fluid secretion. On first pass through the liver 30% to 80% of serotonin is metabolized, predominately to 5-hydroxyindoleacetic acid (5-HIAA), which is excreted by the kidneys. Ninety percent of the remainder is metabolized in the lungs, also to 5-HIAA. Of the remaining 10%, almost all is taken up by platelets, where it remains until it is released during clotting, promoting further platelet aggregation.

 

The main diseases that may be associated with measurable increases in serotonin are neuroectodermal tumors, in particular tumors arising from EC-cells, which are termed carcinoids. They are subdivided into foregut carcinoids, arising from respiratory tract, stomach, pancreas, or duodenum (approximately 15% of cases); midgut carcinoids, occurring within jejunum, ileum, or appendix (approximately 70% of cases); and hindgut carcinoids, which are found in the colon or rectum (approximately 15% of cases). The enzyme 5-HTP decarboxylase, which converts the intermediate 5-HTP to serotonin, is present in midgut tumors, but is absent or present in low concentrations in foregut and hindgut tumors.

 

Carcinoids display a spectrum of aggressiveness with no clear distinguishing line between benign and malignant. The majority of carcinoid tumors do not cause significant clinical disease. Those tumors that behave more aggressively tend to cause nonspecific GI disturbances, such as intermittent pain and bloating, for many years before more overt symptoms develop. In advanced tumors, morbidity and mortality relate as much, or more, to the biogenic amines, chiefly serotonin, and peptide hormones secreted, as to local and distant spread. The symptoms of this so-called carcinoid syndrome consist of flushing, diarrhea, right-sided valvular heart lesions, and bronchoconstriction. All of these symptoms are at least partly caused by serotonin. The carcinoid syndrome is usually caused by midgut tumors, as foregut and hindgut neoplasms produce far lesser amounts of serotonin. Because midgut tumors drain into the portal circulation, which passes into the liver, undergoing extensive hepatic (first-pass) serotonin degradation, symptoms do not usually occur until liver or other distant metastases have developed, producing serotonin that bypasses the hepatic degradation.

 

Serotonin production by disseminated carcinoid tumors can sometimes be so substantial that body tryptophan stores become depleted and clinical tryptophan deficiency, resembling pellagra (triad of diarrhea, dementia, and dermatitis), develops.

 

Diagnosis of carcinoid tumors with symptoms suggestive of carcinoid syndrome rests on measurements of circulating and urine serotonin, urine 5-HIAA (HIAA / 5-Hydroxyindoleacetic Acid [5-HIAA], 24 Hour, Urine), and serum chromogranin A (CGAK / Chromogranin A, Serum), a peptide that is cosecreted alongside specific hormones by neuroectodermal cells. Urine serotonin is, in most circumstances, the least likely marker to be elevated (see Interpretation).

Interpretation

It is usually impossible to diagnose asymptomatic, small carcinoid tumors by measurement of serum or urine serotonin, urine 5 hydroxyindoleacetic acid (5-HIAA), or serum chromogranin A. By contrast, 1 or more of these markers are elevated in most patients with more advanced and symptomatic tumors, usually to levels several times the upper limit of the reference interval.

 

In patients with advanced and symptomatic tumors the following patterns of tumor marker elevations are observed:

-Serum or whole blood serotonin is elevated in nearly all patients with midgut tumors, but only in approximately 50% of those with foregut carcinoids, and in no more than 20% of individuals with hindgut tumors, because foregut and hindgut tumors often have low or absent 5-hydroxytryptophan (5-HTP) decarboxylase activity and, therefore, may produce little, if any, serotonin.

-Urine 5-HIAA is elevated in almost all carcinoid-syndrome patients with midgut tumors, in about 30% of individuals with foregut carcinoids, but almost never in hindgut tumors.

-Serum chromogranin A measurements are particularly suited for diagnosing hindgut tumors, being elevated in nearly all cases, even though serotonin and 5-HIAA are often normal. Chromogranin A is also elevated in 80% to 90% of patients with symptomatic foregut and midgut tumors.

-Urine serotonin is in most circumstances the least likely marker to be elevated. The exception is tumors (usually foregut tumors) that produce predominately 5-HTP, rather than serotonin, and also secrete little, if any, chromogranin A. In this case, circulating chromogranin A, circulating serotonin levels, and urine 5-HIAA levels would not be elevated. However, the kidneys can convert 5-HTP to serotonin, leading to high urine serotonin levels.

 

Urine serotonin measurements are not commonly employed in carcinoid tumor follow-up. The exceptions are patients with tumors that almost exclusively secrete 5-HTP, as summarized above. In these individuals, urine serotonin is the tumor marker of choice to monitor disease progression.

 

In all other patients, disease progression is monitored best using urinary 5-HIAA and serum chromogranin A measurements. These markers are usually proportional to the patient's tumor burden over a wide range of tumor extent and tumor secretory activity.

Clinical Reference

1. Kema IP, Schellings AM, Meibotg G, et al: Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites. Clin Chem 1992;38(9):1730-1736

2. Kema IP, de Vries EG, Muskiet FA: Clinical chemistry of serotonin and metabolites. J Chromatogr 2000;747(1-2):33-48

3. Meijer WG, Kema IP, Volmer M, et al: Discriminating capacity of indole markers in the diagnosis of carcinoid tumors. Clin Chem 2000;46(10):1588-1596

4. Ganim RB, Norton JA: Recent advances in carcinoid pathogenesis, diagnosis and management. Surg Oncol 2000;9(4):173-179

5. Carling RS, Degg TS, Allen KR, et al: Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem 2002;39(Pt 6):577-582

Analytic Time

4 days

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Urine Preservative Collection Options

Ambient

No

Refrigerated

Preferred

Frozen

Yes

6N HCl

No

50% Acetic Acid

Preferred

Na2CO3

No

Toluene

Yes

6N HNO3

Yes

Boric Acid

No

Thymol

No

Forms

If not ordering electronically, complete, print, and send an Oncology Test Request Form (T729) with the specimen

(http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)