What are the causes of elevated Hydroxyindoleacetic acid (5-HIAA)?

From the Guidelines

Elevated HEIC acid levels are primarily caused by conditions affecting dopamine metabolism in the body, with the main causes including certain neuroendocrine tumors, Parkinson's disease treatment, and genetic disorders affecting catecholamine metabolism. The causes of elevated HEIC acid levels can be broken down into several key categories:

• Neuroendocrine tumors, such as pheochromocytomas and neuroblastomas, which produce excess catecholamines that metabolize into HEIC acid 1
• Parkinson's disease treatment with levodopa, which can significantly increase HEIC acid levels as the medication is converted to dopamine and then metabolized
• Various medications that affect dopamine pathways, including antipsychotics and some antidepressants, which may alter HEIC acid levels
• Genetic disorders affecting catecholamine metabolism, such as aromatic L-amino acid decarboxylase deficiency, which can lead to abnormal HEIC acid levels
• Stress, both physical and psychological, which can temporarily increase catecholamine production, potentially elevating HEIC acid
• Certain foods rich in vanillin or catecholamine precursors, which may influence levels, though dietary effects are typically minimal compared to pathological causes
• Kidney dysfunction, which can cause elevated levels due to decreased excretion, as HEIC acid is primarily eliminated through the kidneys 1 When elevated HEIC acid is detected, further diagnostic workup is typically needed to determine the underlying cause, often including imaging studies and additional biochemical testing to identify potential tumors or metabolic disorders 1.

From the FDA Drug Label

1. 2 Pharmacodynamics In healthy subjects, telotristat ethyl 500 mg three times daily (twice the recommended dosage) for 14 days decreased whole blood serotonin and 24-hour urinary 5-hydroxyindolacetic acid (u5-HIAA) from baseline.

The causes of elevated HEIC acid (also known as 5-hydroxyindolacetic acid or 5-HIAA) are not directly stated in the provided text, but it can be inferred that an overproduction of serotonin may lead to elevated levels of 5-HIAA, as telotristat ethyl reduces the production of peripheral serotonin and subsequently decreases 24-hour u5-HIAA.

• Key points:
  • Serotonin overproduction may lead to elevated 5-HIAA levels.
  • Telotristat ethyl reduces serotonin production, which in turn decreases 24-hour u5-HIAA. 2

From the Research

Causes of Elevated 5-Hydroxyindoleacetic Acid (5-HIAA)

• Elevated 5-HIAA levels are associated with carcinoid syndrome, a condition caused by the release of serotonin and other substances from well-differentiated neuroendocrine tumors (NETs) 3
• The serotonin pathway plays a central role in the pathophysiology of carcinoid syndrome, and alteration of this pathway can lead to elevated 5-HIAA levels 4
• Neuroendocrine tumors (NETs) that metastasize to the liver can cause an increase in serotonin production, leading to elevated 5-HIAA levels 5
• The release of hormones and other products from NETs, including serotonin, can lead to elevated 5-HIAA levels 6

Relationship Between 5-HIAA Levels and Carcinoid Syndrome

• Elevated 5-HIAA levels are a diagnostic marker for carcinoid syndrome 4
• Higher 5-HIAA levels are associated with disease progression and increased risk of mortality in patients with carcinoid heart disease 6
• The accuracy of diagnostic methods for assessing 5-HIAA levels can be improved by considering new serotonin precursors or metabolites as diagnostic markers 4

Clinical Implications of Elevated 5-HIAA Levels

• Elevated 5-HIAA levels can be used as a prognostic marker for patients with carcinoid syndrome 6
• Management of 5-HIAA levels is important in patients with carcinoid syndrome, and treatment options include somatostatin analogs and serotonin synthesis inhibitors 7
• Elevated 5-HIAA levels can be associated with increased symptoms and reduced quality of life in patients with carcinoid syndrome 5