Carcinoid syndrome

Overview

Carcinoid syndrome is a rare condition that occurs when a carcinoid tumor—a slow-growing type of neuroendocrine tumor—produces and releases hormones such as serotonin into the bloodstream. These tumors most often originate in the gastrointestinal tract or lungs. Carcinoid syndrome typically develops when the tumor has metastasized (spread), especially to the liver, which allows hormone byproducts to bypass normal liver metabolism and circulate systemically, causing a range of symptoms. While the tumors themselves may grow slowly, the hormone-related effects can significantly affect a patient’s quality of life.

Causes

Carcinoid syndrome is caused by the excessive secretion of serotonin and other vasoactive substances (e.g., histamine, tachykinins, prostaglandins) from carcinoid tumors into the bloodstream. Normally, these substances are broken down by the liver. However, when the tumor metastasizes to the liver or other areas where it bypasses hepatic metabolism, the substances enter the systemic circulation and trigger symptoms. Key causes include:

• Metastatic carcinoid tumors: Most commonly arising from the small intestine, appendix, rectum, or lungs

• Liver metastasis: Essential for most systemic symptoms, as it allows hormone bypass of first-pass liver metabolism

• Primary lung carcinoid tumors: Can cause carcinoid syndrome without liver involvement

Symptoms

The hallmark symptoms of carcinoid syndrome are related to the release of serotonin and other bioactive substances into the bloodstream. Common features include:

• Flushing: Sudden redness or warmth, usually of the face and neck, often triggered by stress, alcohol, or certain foods

• Diarrhea: Frequent, watery bowel movements, sometimes leading to dehydration

• Wheezing or asthma-like symptoms: Due to bronchoconstriction

• Abdominal cramping and pain

• Heart valve lesions: Mainly affecting the right side of the heart (tricuspid and pulmonary valves), leading to carcinoid heart disease

• Fatigue and weight loss

• Pellegra-like skin symptoms: Due to niacin deficiency from excessive serotonin production

Diagnosis

Diagnosis of carcinoid syndrome involves identifying both the hormone-producing tumor and its systemic effects. Key diagnostic steps include:

• 24-hour urine test for 5-HIAA (5-hydroxyindoleacetic acid): A metabolite of serotonin, elevated in most cases

• Blood tests: May include chromogranin A (a tumor marker), serotonin levels, and liver function tests

• Imaging studies:

  • CT or MRI scans to locate primary and metastatic tumors

  • Somatostatin receptor scintigraphy (Octreoscan) or PET/CT using gallium-68 DOTATATE for tumor localization

• Echocardiogram: To assess for carcinoid heart disease if cardiac symptoms are present

• Endoscopy or colonoscopy: For direct visualization and biopsy of tumors within the GI tract

Treatment

Treatment of carcinoid syndrome focuses on controlling symptoms, reducing hormone production, and managing the underlying tumor. Options include:

• Somatostatin analogs: Octreotide or lanreotide are first-line therapies that suppress hormone release and alleviate symptoms

• Surgical removal: If feasible, resection of the primary tumor or metastatic deposits (especially in the liver)

• Hepatic artery embolization: To reduce blood supply to liver metastases and decrease hormone output

• Peptide receptor radionuclide therapy (PRRT): Targeted radiation therapy using radiolabeled somatostatin analogs

• Interferon-alpha: Occasionally used to inhibit tumor growth and hormone production

• Anti-diarrheal medications and dietary adjustments: For symptom relief

• Cardiac management: Valve replacement surgery may be required for advanced carcinoid heart disease

Prognosis

The prognosis for carcinoid syndrome varies depending on the location of the tumor, extent of metastasis, and response to treatment. While carcinoid tumors tend to grow slowly, the syndrome can cause significant complications if left untreated. With effective symptom control and tumor-directed therapy, many patients can live for years after diagnosis. However, long-term issues such as carcinoid heart disease or severe diarrhea may impact quality of life. Early diagnosis and multidisciplinary care are essential for optimal outcomes.