Summary

Carcinoid Syndrome is a clinical syndrome caused by the systemic release of vasoactive substances – primarily Serotonin (5-HT) – from Neuroendocrine Tumours (NETs). NETs most commonly arise in the midgut (Appendix, Ileum), but can occur in the foregut (Lung, Stomach) or hindgut (Rectum). The syndrome typically only manifests when the tumour has metastasised to the liver, allowing serotonin to bypass hepatic metabolism and enter the systemic circulation. Cardinal features include paroxysmal flushing, secretory diarrhoea, wheezing (bronchospasm), and right-sided valvular heart disease (Carcinoid Heart Disease). Diagnosis is by measuring 24-hour Urinary 5-HIAA (a serotonin metabolite) and Chromogranin A. Treatment involves Somatostatin Analogues (Octreotide, Lanreotide) to control symptoms, surgical resection where possible, and perioperative Octreotide to prevent Carcinoid Crisis.

Key Facts

• Tumour Origin: Midgut NETs (Appendix, Ileum) most common to cause syndrome.
• Syndrome Appears: Usually only after Liver Metastases (Hepatic metabolism bypassed).
• Secreted Substances: Serotonin (5-HT), Histamine, Bradykinin, Prostaglandins, Tachykinins.
• Classic Triad: Flushing, Diarrhoea, Bronchospasm.
• Heart: Carcinoid Heart Disease – Right-sided valve fibrosis (Tricuspid Regurgitation, Pulmonary Stenosis). Left heart spared (Lungs metabolise serotonin).
• Diagnosis: 24h Urinary 5-HIAA (>25 µmol/24h), Chromogranin A.
• Treatment: Somatostatin Analogues (Octreotide/Lanreotide). Surgery. PRRT.

Clinical Pearls

"No Liver Mets = No Syndrome": Serotonin from gut NETs is cleared by the liver. Carcinoid syndrome typically only occurs when there are liver metastases (or a lung primary, which drains directly to systemic circulation).

"Right Heart Valve Fibrosis – Left Heart Spared": Serotonin is metabolised by MAO in the lungs. So valves exposed before the lungs (Tricuspid, Pulmonary) are damaged. Left-sided valves are protected.

"Avoid the Crisis": Carcinoid Crisis (Severe flushing, Hypotension, Bronchospasm) is triggered by anaesthesia, surgery, or tumour manipulation. Prevent with Octreotide infusion.

"Tryptophan Thievery": NETs consume Tryptophan to make Serotonin. This can cause Pellagra (Niacin deficiency – 3Ds: Dermatitis, Diarrhoea, Dementia).

Why This Matters Clinically

Carcinoid syndrome is often a sign of metastatic disease, requiring MDT management. Recognising the syndrome early, avoiding triggers for crisis, and using somatostatin analogues can dramatically improve quality of life.

Key Examination Findings

Differential Diagnosis (Flushing)

• 5-Year Survival (All NETs): ~60-70%. Depends on grade, stage, primary site.
• 5-Year Survival (Metastatic Midgut with Syndrome): ~50%.
• CHD Worsens Prognosis: Significantly reduces survival.
• Prognosis Improving: With PRRT, targeted therapies, and MDT care.

Prognostic Factors

Follow-Up Schedule

Nutritional Considerations

Key Counselling Points (Extended)

1. Symptom Control: "The monthly injection should significantly reduce your flushing and diarrhoea."
2. Heart Monitoring: "We will do yearly heart scans – the hormones can affect your heart valves over time."
3. Surgery Safety: "If you ever need any operation, even a dental procedure, tell your doctors you have Carcinoid Syndrome. You need a special drip to prevent a dangerous reaction."
4. Avoid Triggers: "Alcohol and extreme stress can trigger flushing. Try to minimise these."
5. Long-Term Condition: "This is a chronic condition, but many people live well for many years with proper treatment."
6. MDT Care: "You will be looked after by a team including cancer specialists, hormone doctors, and sometimes heart doctors."

Patient FAQs

Common Clinical Pitfalls

Key Guidelines

Landmark Trials

Scenario 1:

• Stem: A 60-year-old man presents with episodic dry facial flushing, watery diarrhoea, and wheeze. He has a palpable liver. Echo shows Tricuspid Regurgitation. What is the likely diagnosis and how would you confirm it?
• Answer: Carcinoid Syndrome (Metastatic Midgut NET). Confirm with 24-hour Urinary 5-HIAA, Chromogranin A, and CT Abdomen +/- Gallium-68 DOTATATE PET/CT.

Scenario 2:

• Stem: Why does Carcinoid Syndrome typically only occur with liver metastases?
• Answer: Serotonin from midgut NETs is normally cleared by the liver (First-Pass Metabolism). When tumour cells metastasise TO the liver, they secrete serotonin directly into hepatic veins, bypassing portal clearance and reaching the systemic circulation.

Scenario 3:

• Stem: What cardiac lesions are seen in Carcinoid Heart Disease, and why is the left side spared?
• Answer: Right-Sided Valves: Tricuspid Regurgitation, Pulmonary Stenosis. Serotonin is metabolised by MAO in the lungs, so left-sided valves (Mitral, Aortic) are protected.

Scenario 4:

• Stem: A patient with Carcinoid Syndrome requires surgery. How do you prevent Carcinoid Crisis?
• Answer: IV Octreotide Infusion (50-100 µg/hr) started before anaesthesia and continued throughout surgery. Avoid catecholamine-releasing agents. Bolus Octreotide if crisis occurs.

What is Carcinoid Syndrome?

Carcinoid Syndrome is caused by a type of tumour called a Neuroendocrine Tumour (NET) that releases hormones (like serotonin) into your bloodstream. This usually happens when the tumour has spread to the liver.

What are the symptoms?

• Flushing: Sudden redness of the face and neck, without sweating.
• Diarrhoea: Frequent, watery loose stools.
• Wheezing: Difficulty breathing, like asthma.
• Heart problems: The hormones can damage the heart valves over time.

How is it treated?

• Monthly injections (Octreotide/Lanreotide): These block the hormone release and control symptoms.
• Surgery: To remove the tumour and any spread to the liver, if possible.
• Special scans and treatments: Targeted radiation therapy for the tumour.

Key Counselling Points

1. Symptom Control: "The injections should significantly reduce your flushing and diarrhoea."
2. Heart Monitoring: "We will do regular heart scans to check your valves."
3. Surgery Safety: "If you need any operation, tell your doctors about your condition. You'll need a special infusion to prevent a crisis."
4. Avoid Triggers: "Alcohol and stress can trigger flushing."

• Siegfried Oberndorfer (1907): First described "Karzinoide" (Carcinoid) tumours as less aggressive than typical carcinomas.
• Björck & Thorson (1952): First described the clinical syndrome of flushing, diarrhoea, and right-sided heart disease associated with carcinoid tumours.
• Somatostatin Analogues (1980s): Revolutionised symptom control.
• PRRT (2000s): Lu-177 DOTATATE provided targeted treatment for somatostatin receptor-positive tumours.