Carcinoid syndrome

Rare paraneoplastic syndrome caused by metastatic serotonin-secreting neuroendocrine tumors (carcinoids), typically of midgut origin with liver metastases, leading to episodic flushing, secretory diarrhea, bronchospasm, and fibrotic right-sided heart valve lesions.

• Though uncommon, carcinoid syndrome is a classic cause of unexplained flushing and diarrhea. Its presence usually signifies advanced malignancy (often already with liver metastases) and can lead to serious complications like carcinoid heart disease (cause of morbidity) and niacin deficiency. Early recognition allows for appropriate imaging, somatostatin analog therapy, and possible tumor resection to improve outcomes.

• Episodic cutaneous flushing of the face/neck (red to violaceous); often triggered by stress, alcohol, or certain foods.
• Diarrhea (intermittent, secretory) with abdominal cramping; can lead to electrolyte disturbances and weight loss.
• Bronchospasm causing wheezing and dyspnea (asthma-like episodes), often accompanying flushing.
• Fibrosis of the right heart valves (due to serotonin) causing tricuspid regurgitation and pulmonary stenosis (jugular venous distension, edema); left heart is typically spared (lung metabolism of serotonin).
• Advanced cases: pellagra (dermatitis, diarrhea, dementia from niacin deficiency) due to tryptophan being diverted to serotonin.

1. Biochemical confirmation: 24-hour urinary 5-HIAA (serotonin metabolite) is the best initial test (avoid serotonin-rich foods before test); plasma 5-HIAA or serum chromogranin A can be supportive.
2. Localize the tumor: imaging with contrast CT/MRI of the abdomen and somatostatin receptor nuclear scan (octreotide scan or ⁶⁸Ga-DOTATATE PET) to identify primary lesion and metastases.
3. Evaluate extent and complications: perform echocardiography to assess carcinoid heart disease if murmurs or symptoms; check vitamin B3 levels if pellagra signs are present.
4. Avoid triggers: counsel on avoiding alcohol and triggering foods (e.g., red wine, chocolate, nuts, cheese) that can precipitate flushing.
5. Peri-procedural care: administer prophylactic octreotide before anesthesia or invasive procedures to prevent a carcinoid crisis (massive hormone release causing shock).

1. Acute carcinoid crisis (severe flushing, bronchospasm, hypotension): prompt IV octreotide to abort the episode, plus supportive care (fluids, airway support, antihistamines/bronchodilators).
2. Chronic management: long-acting somatostatin analogs (octreotide, lanreotide) to control hormone secretion and relieve symptoms; add oral telotristat (tryptophan hydroxylase inhibitor) if diarrhea remains severe.
3. Surgical therapy: resection of primary tumor and metastases when feasible (e.g., remove bowel tumor, hepatic metastasectomy or embolization) offers best chance at symptom control.
4. Advanced/metastatic disease: consider PRRT (peptide receptor radionuclide therapy with Lutetium-177) for somatostatin receptor–positive tumors; targeted therapies (e.g., everolimus) or interferon-alpha in select cases. Manage complications: replace niacin, and perform valve surgery if heart failure is advanced.

• Classic rule of thirds for carcinoid tumors: ~1/3 are multiple, ~1/3 metastasize (and can cause syndrome), and ~1/3 present with a second malignancy.
• Tryptophan steal: Excess serotonin production by the tumor depletes tryptophan, leading to niacin (vitamin B3) deficiency → pellagra (Dermatitis, Diarrhea, Dementia).

• Profound flushing, bronchospasm, and hypotension during surgery or biopsy in a NET patient = carcinoid crisis – require emergent octreotide, IV fluids, and pressors to prevent cardiovascular collapse.
• Signs of right-sided heart failure (worsening edema, ascites, neck vein distension) in a carcinoid patient – suggests progressing carcinoid heart disease; urgent cardiac evaluation (echo) and consideration of valve replacement.

1. Episodic flushing + diarrhea + wheezing → suspect carcinoid syndrome.
2. Obtain 24h urine 5-HIAA test (confirm excess serotonin).
3. If 5-HIAA is elevated → perform imaging (CT/MRI) + somatostatin receptor scan to locate tumor and metastases.
4. Begin octreotide to control symptoms; refer to oncology/surgery for tumor-directed therapy (resection if localized, etc.).
5. For any invasive procedure or if high risk, give prophylactic octreotide to prevent crisis; provide niacin supplementation if needed; periodic echocardiograms to monitor heart.

• Middle-aged adult with recurrent flushing, wheezing, diarrhea, and a new murmur of tricuspid regurgitation; elevated 5-HIAA levels → Carcinoid syndrome from a metastatic small intestinal NET.
• Patient with a history of carcinoid tumor develops a photosensitive rash, glossitis, diarrhea, and mental status changes → niacin deficiency (pellagra) due to carcinoid syndrome.