5-Hydroxyindoleacetic Acid (HIAA), Quantitative, 24-Hour Urine

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Turnaround Time: 4 - 8 days
CPT Code:


Test Type: 4 mL aliquot Urine (24-hour)
Stability Time:



Room temperature

7 days


14 days


14 days

Freeze/thaw cycles

Stable x3

Reference Range:

0.0−14.9 mg/24 hours

If a borderline elevation of 5-HIAA is found, sample should be recollected following withdrawal of dietary and medication sources that might elevate 5-HIAA (see Patient Preparation). Nontropical sprue may cause a slight increase in urinary 5-HIAA. 5-HIAA levels are lowered by renal insufficiency and after small bowel resection. When a patient strongly suspected for carcinoid syndrome shows normal or borderline increases of 5-HIAA, two possibilities should be considered: one, that large amounts of serotonin produced are not being metabolized, in which case blood levels of serotonin are required to document the diagnosis; and two, that secretion of 5-HIAA by the tumor is intermittent, in which case repeat timed specimen collections are needed to demonstrate the abnormality.


Levels of 5-HIAA may not be elevated in nonfunctional tumors. Because flushing is mediated by different hormones in foregut and midgut tumors, some patients with a neuroendocrine tumors will have symptoms of flushing with low or normal levels of 5-HIAA. A number of substances interfere with determination of urinary 5-HIAA.1

Causes of Elevated 5-HIAA:

Foods: Avocado, bananas, eggplant, kiwi fruit, nuts (hickory nuts, pecans, walnuts), pineapple, plums, tomato products.

Drugs: Acetaminophen (Tylenol®), antihistamines (nasal drops and spray), antihypertensives, antipsychotics, caffeine, cough suppressants, diazepam (Valium®), muscle relaxants, nicotine, warfarin (Coumadin®)

Causes of Diminished 5-HIAA:

• Alcohol, aspirin, antidepressants (imipramine, monoamine oxidase inhibitors), herbal products: Diadzin (active compound in kudzu, a Chinese herbal treatment for alcohol abuse), St John's wort

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Serotonin measurement is used in conjunction with urinary 5-hydroxyindoleacetic acid (5-HIAA) and/or serum chromogranin A in the diagnosis of carcinoid syndrome. Carcinoid tumors are slow-growing neuroendocrine tumors derived from enterochromaffin cells that are widely distributed throughout the body.1-4 Approximately 65% of carcinoid tumors are found in the gastrointestinal tract from the foregut, midgut, and hindgut and another 25% originate in the bronchopulmonary tract.2,4 About a quarter of cases present with distant metastases, half of which have unknown primary tumor location.2 Carcinoid tumors secrete a variety of peptides and small molecules.1,4,5,6 Midgut carcinoid tumors frequently produce serotonin. Serotonin-secreting carcinoids from other locations are less common. Serotonin (5-hydroxy-tryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin secretion in the gut causes an increase in gastrointestinal blood flow, motility, and fluid secretion. In healthy individuals, the great majority of serotonin made by the gut is converted by the liver and lungs to 5-hydroxy-indoleacetic acid (5-HIAA) via first pass metabolism prior to entering the general circulation.

Serotonin secreting carcinoid tumors are relatively slow growing, and in most cases, asymptomatic.1,4,5 The local, paracrine effect of increased serotonin on the gut intestine can cause diarrhea, malabsorption, and tumor mass producing discomfort.4,7 Since most serotonin produced by carcinoid tumors is metabolized prior to reaching the circulation, the metabolic product, 5-HIAA in a 24-hour urine collection is usually the most important marker for diagnosing and monitoring treatment of the carcinoid syndrome.4,8 The severity of carcinoid syndrome symptoms correlates with the level of 5-HIAA in urine. Urine 5-HIAA has been shown to have a sensitivity of 73% and specificity of 100% for diagnosing well-differentiated functional gastroenterohepatic neuroendocrine tumors.9 Compared with patients having normal urinary 5-HIAA levels, patients with elevated levels, whether symptomatic or not, tend to have poorer prognosis.10-12

In cases where a larger amount of serotonin reached the systemic circulation (advanced disease with liver metastases bypassing first pass metabolism), patients can present with a constellation of symptoms referred to as the carcinoid syndrome. The carcinoid syndrome can also occur in the absence of liver metastases in cases where tumor pathology causes direct venous drainage of serotonin bypassing first pass liver metabolism.6,13 Carcinoid syndrome is relatively rare and is most commonly associated with midgut carcinoid tumors.3,4 Carcinoid syndrome occurs in 20% of cases of well-differentiated endocrine tumors of the jejunum or ileum.6,13 Carcinoid syndrome occurs less often with neuroendocrine tumors of other origins and is very rare in association with rectal neuroendocrine tumors.6,13 Carcinoid syndrome is characterized by one or more symptoms, including diarrhea, dry flushing without sweating with or without palpitations, and intermittent abdominal pain.6 Some patients also experience lacrimation and rhinorrhea.6,13 Advanced or long-standing carcinoid syndrome can lead to carcinoid heart disease involving the tricuspid and pulmonary valves of the heart.7 Significant elevations in urine 5-HIAA have been associated with carcinoid heart disease.14-16 Other cardiovascular complications include bowel ischemia and hypertension.7 Approximately one in five patients with carcinoid syndrome present with heart disease at diagnosis.6,13 Carcinoid tumors are classified similarly, whether they produce symptoms of the carcinoid syndrome or not.17

In healthy individuals, approximately 99% of dietary tryptophan is metabolized by the oxidative pathway into nicotinic acid (vitamin B3).4 In carcinoid tumors, excessive conversion of tryptophan to serotonin can cause result in vitamin B3 deficiency referred to as pellagra, a condition that is characterized by a triad of symptoms: diarrhea, dementia, and dermatitis.18

1. Aggarwal G, Obideen K, Wehbi M. Carcinoid tumors: What should increase our suspicion? Cleve Clin J Med. 2008 Dec; 75(12):819-855. PubMed 2421946

2. Modlin IM, Lye KD, Kidd M. A 50-year analysis of 562 gastric carcinoids: Small tumor or larger problem? Am J Gastroenterol. 2004 Jan; 99(1):23-32. PubMed 2421946

3. Robertson RG, Geiger WJ, Davis NB. Carcinoid tumors. Am Fam Physician. 2006 Aug 1; 74(3):429-434. PubMed 2421946

4. Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: A clinical review. Oncologist. 2005 Feb; 10(2):123-131. PubMed 2421946

5. Ghevariya V, Malieckal A, Ghevariya N, Mazumder M, Anand S. Carcinoid tumors of the gastrointestinal tract. South Med J. 2009 Oct; 102(10):1032-1040. PubMed 2421946

6. Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012 Jan; 61(1)6-32. PubMed 2421946

7. van der Horst-Schrivers AN, Wymenga AN, Links TP, Willemse PH, Kema IP, de Vries EG. Complications of midgut carcinoid tumors and carcinoid syndrome. Neuroendocrinology. 2004; (80 Suppl)1:28-32. PubMed 2421946

8. Bajetta E, Ferrari L, Martinetti A, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumours. Cancer. 1999 Sep 1; 86(5):858-865. PubMed 2421946

9. Feldman JM, O'Dorisio TM. Role of neuropeptides and serotonin in the diagnosis of carcinoid tumours. Am J Med. 1986 Dec 22; 81(6B):41-48. PubMed 2421946

10. Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol 2005 Mar 1; 89(3):151-160. PubMed 2421946

11. Agranovich AL, Anderson GH, Manji M, Acker BD, Macdonald WC, Threlfall WJ. Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome. J Surg Oncol. 1991 May; 47(1):45-52. PubMed 2421946

12. Janson ET, Holmberg L, Stridsberg M, et al. Carcinoid tumors: Analysis of prognostic factors and survival in 301 patients from a referral center. Ann Onco

Collection Details:

Patient Preparation:

Avoid bananas, avocados, plums, eggplant, tomatoes, avocados plums, eggplant, tomatoes, plantain, pineapple, walnuts, and interfering drugs for a 72 hour period prior to and during collection. Foods and medications associated with altered urinary HIAA results: Decreased HIAA: Aspirin, chlorpromazine (Thorazine), corticotropin, dihydroxyphenylacetic acid, alcohol, gentisic acid, homogentisic acid, hydrazine derivatives, imipramine (Tofranil®), <isocarboxazid (Marplan), keto acids, levodopa, MAO inhibitors, methenamine methyldopa (Aldomet®), perchlorperazine, phenothiazines (Compazine®), promazine, promethazine (Mepergan®). Increased HIAA: Acetaminophen, acetanilide, caffeine, coumaric acid, diazepam (Valium®), ephedrine, fluorouracil glycerol guaiacolate (Guaifenesin), melphalan (Alkeran®), mephenesin, methamphetamine (Desoxyn), methocarbamol (Robaxin®), naproxen, nicotine, phenacetin, phenmetrazine, phenobarbital, phentolamine, rauwolfia, reserpine.

Collection Instructions:

Measure and record total 24-hour urine volume on the request form.

Plastic urine container, no preservative (Note: 1 g/L boric acid may be added as a preservative for other tests without harm to 5-HIAA.)

Instruct the patient to void at 8 AM and discard the specimen. Then collect all urine including the final specimen voided at the end of the 24-hour collection period (ie, 8 AM the next morning). Screw the lid on securely. Label container with patient's name, date, and time. Measure and record total urine volume. Mix well; send aliquot.

Room temperature.