5-HIAA Test – Purpose, Normal Range, and Carcinoid Syndrome Diagnosis

Overview

The 5-HIAA (5-Hydroxyindoleacetic Acid) test is an important diagnostic tool that helps detect and monitor certain rare types of tumors called carcinoid tumors. These tumors produce serotonin, a chemical that regulates mood, digestion, and several body functions. When serotonin is broken down, it forms 5-HIAA, which is released into the urine.

By measuring the amount of 5-HIAA in the urine, doctors can evaluate whether the body is producing excessive serotonin — a common sign of carcinoid syndrome.

What is 5-HIAA?

5-HIAA (5-Hydroxyindoleacetic Acid) is a metabolite (breakdown product) of serotonin, a neurotransmitter or chemical messenger that helps regulate mood, sleep, appetite, and digestion.

The 5-HIAA test is mainly used to detect or monitor carcinoid tumors — rare serotonin-producing tumors found mostly in the gastrointestinal tract (especially the small intestine) or lungs.

When carcinoid tumors produce too much serotonin, it leads to increased levels of 5-HIAA in urine, which helps doctors confirm the diagnosis.

Where is 5-HIAA Produced in the Body?

• Serotonin Production:
  Serotonin is produced mainly in enterochromaffin cells located in the lining of the gastrointestinal tract, and to a smaller extent in certain parts of the brain.
• Conversion to 5-HIAA:
  Once serotonin has completed its role, it travels to the liver, where it is metabolized (broken down) into 5-HIAA.
• Excretion:
  The body then eliminates 5-HIAA through the urine, making urine testing the most accurate method to measure it.

Main Functions and Importance of the 5-HIAA Test

The 5-HIAA test plays a key role in identifying and managing serotonin-producing tumors. Here are the main uses:

1. Detect Carcinoid Syndrome:
   High levels of 5-HIAA in urine are a hallmark of carcinoid syndrome, caused by tumors that produce excessive serotonin.
2. Monitor Treatment Effectiveness:
   After surgery or therapy for carcinoid tumors, repeated testing of 5-HIAA helps monitor how well the treatment is working. Decreasing levels indicate successful treatment.
3. Identify Hormonal Overproduction Symptoms:
   In cases of unexplained flushing, chronic diarrhea, or wheezing, the 5-HIAA test helps identify whether a hormone-producing tumor might be the cause.
4. Differentiate Between Causes:
   The test can help rule out non-carcinoid causes of similar symptoms, such as food allergies or irritable bowel syndrome (IBS).

Causes of Low 5-HIAA Levels

Low or normal levels of 5-HIAA usually mean that serotonin metabolism is functioning normally. Some possible causes of low 5-HIAA include:

• Normal metabolism: Healthy individuals naturally have low levels.
• Certain medications: Drugs such as monoamine oxidase inhibitors (MAOIs) can reduce 5-HIAA production.
• Serotonin deficiency: Though rare, conditions that lower serotonin production may also reduce 5-HIAA levels.

Symptoms of Low 5-HIAA Levels

• Generally asymptomatic:
  Low 5-HIAA levels usually do not cause any symptoms.
• If clinically significant:
  If serotonin deficiency is present, symptoms like mood changes, depression, or sleep disturbance may occur, but these are rare in the context of this test.

Causes of High 5-HIAA Levels

Increased levels of 5-HIAA can indicate an overproduction of serotonin in the body. The main causes include:

1. Carcinoid Tumors (Most Common):
   These tumors, especially those originating in the small intestine, appendix, colon, or lungs, release excessive serotonin, which leads to high urinary 5-HIAA levels.
2. Other Neuroendocrine Tumors:
   Rare tumors of the pancreas or bronchial system may also secrete serotonin and elevate 5-HIAA.
3. Dietary Factors (False Positives):
   Eating foods high in serotonin before the test — such as bananas, pineapples, walnuts, avocados, tomatoes, and plums — can temporarily raise 5-HIAA levels.
4. Medications:
   Some drugs, including acetaminophen (paracetamol) and caffeine, can affect results if taken before the test.

Symptoms of High 5-HIAA Levels (Carcinoid Syndrome)

When 5-HIAA levels are high due to carcinoid syndrome, patients may experience the following symptoms:

• Flushing of the skin: Sudden redness and warmth of the face or neck.
• Diarrhea: Frequent, watery stools, often chronic.
• Abdominal cramps: Due to excessive serotonin affecting digestion.
• Wheezing or asthma-like breathing problems: Caused by serotonin’s effect on airways.
• Rapid heartbeat (Palpitations): May occur during flushing episodes.

These symptoms are often intermittent and may worsen after eating or stress.

Reference Ranges for 5-HIAA Test

The 5-HIAA test is most commonly done using a 24-hour urine collection to accurately measure excretion.

Sample Type and Test Method

• Sample Type: 24-hour urine sample (most common method).
• Alternative: Blood (plasma) 5-HIAA levels may be checked in specific situations.
• Container: A special container with preservatives is provided for urine collection.
• Testing Method: Usually performed using liquid chromatography or mass spectrometry for accuracy.

Test Preparation

To ensure accurate results, patients are advised to follow certain precautions before and during the 24-hour urine collection:

1. Dietary Restrictions (for 2–3 days before test):

Avoid foods rich in serotonin, such as:

• Bananas
• Pineapples
• Avocados
• Walnuts
• Tomatoes
• Kiwi
• Plums
• Eggplants

2. Medication Adjustments (if prescribed by doctor):

Avoid medicines like acetaminophen, caffeine, and ephedrine before the test, if possible. Always consult your doctor before stopping any medication.

3. Proper Sample Collection:

• Collect all urine passed in 24 hours in the provided container.
• Keep it refrigerated during collection.
• Return the sample promptly to the lab.

When to Consult a Doctor

You should consult a doctor if you experience any of the following symptoms:

• Frequent flushing of the face or neck.
• Unexplained or persistent diarrhea.
• Wheezing, difficulty breathing, or palpitations.
• Abdominal pain or cramps with no clear cause.

If 5-HIAA levels are elevated, the doctor may recommend imaging tests (CT, MRI, or PET scans) or other hormonal tests to locate and confirm the tumor.

Important Word Explanations

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