What is the significance of 5-HIAA (5-Hydroxyindoleacetic acid)?

From the Guidelines

Elevated 5-HIAA levels are a significant indicator of carcinoid syndrome, and patients with levels of 300 mcmol or greater over 24 hours are more likely to have carcinoid heart disease, as shown in a recent study involving 250 patients with carcinoid syndrome 1. In the context of carcinoid syndrome, 5-HIAA is a crucial marker for diagnosis and monitoring. The measurement of 5-HIAA in urine is a standard diagnostic tool, with normal values typically ranging from 2-8 mg per 24 hours, though reference ranges may vary between laboratories. When interpreting 5-HIAA results, it is essential to consider factors that may interfere with the test, such as certain foods, medications, or other conditions that affect serotonin metabolism. For instance, foods like avocados, bananas, eggplant, pineapples, plums, tomatoes, and walnuts can artificially elevate 5-HIAA levels, while medications like acetaminophen, caffeine, phenothiazines, and serotonin reuptake inhibitors can also impact results. In patients with carcinoid syndrome, a cardiology consultation and echocardiogram should be considered to assess for carcinoid heart disease, especially if 5-HIAA levels are elevated or if there are signs and symptoms of heart disease, as supported by the study 1. Key considerations for 5-HIAA testing include:

• Avoiding certain foods for 3 days before collection
• Collecting all urine over a 24-hour period in a special container with preservative
• Being aware of medications that can interfere with results
• Interpreting results in the context of clinical presentation and other diagnostic findings. The use of somatostatin analogs like octreotide or lanreotide may be recommended for symptom control and potentially to control tumor growth in patients with clinically significant tumor burden or progressive disease, as shown in studies like the PROMID and CLARINET trials 1.

From the Research

5-HIAA and Carcinoid Syndrome

• 5-HIAA (5-hydroxyindoleacetic acid) is a biochemical marker used to assess the activity of carcinoid tumors and the effectiveness of treatment in patients with carcinoid syndrome 2, 3, 4, 5, 6.
• Studies have shown that somatostatin analogues, such as octreotide and lanreotide, can effectively reduce urinary 5-HIAA levels and alleviate symptoms of carcinoid syndrome, including flushing and diarrhea 2, 3, 4, 5, 6.
• The reduction in 5-HIAA levels has been observed in 45-46% of patients treated with somatostatin analogues, with a significant decrease in symptoms in 65-72% of patients 6.
• Increasing the dose or frequency of somatostatin analogues or switching to a different somatostatin analogue can lead to further reduction in symptoms in 72-84% of cases 6.
• Other treatments, such as liver-directed therapy, telotristat ethyl, and interferon-alpha, have also been shown to be effective in reducing symptoms and 5-HIAA levels in patients with carcinoid syndrome 6.

Treatment Outcomes

• A study published in 1996 found that lanreotide treatment resulted in a significant decrease in flushing episodes and bowel movements, with 42% of patients experiencing at least a 50% reduction in 5-HIAA values after six months of treatment 2.
• Another study published in 1986 found that treatment with a long-acting somatostatin analogue resulted in a decrease of 50% or more in urinary 5-HIAA levels in 72% of patients, with a median duration of response of more than 12 months 3.
• A 1993 study found that treatment with octreotide alone or in combination with alpha-interferon resulted in a significant reduction in urinary 5-HIAA levels and symptoms in 70% of patients, with a median duration of response of 8-10 months 4.
• A 1995 study analyzed published dose-titration data on octreotide use in carcinoid patients and found that increasing the dose of octreotide is associated with increased benefit with respect to control of flushing, diarrhea, and 5-HIAA levels 5.
• A 2019 systematic review and meta-analysis found that somatostatin analogues, liver-directed therapy, telotristat ethyl, and interferon-alpha are effective treatments for carcinoid syndrome, with response rates ranging from 40% to 84% 6.