Carcinoid syndrome

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How the diagnosis is reached

Episodic flushing, secretory diarrhea and wheeze form the classic triad of carcinoid syndrome, produced by vasoactive mediators, principally serotonin, released from a neuroendocrine tumour. The key to the anatomy is the liver: midgut tumours drain into the portal vein, and hepatic metabolism inactivates their secretions, so systemic symptoms appear only once liver metastases release mediators directly into the systemic circulation. That is why this patient has both an ileal primary and extensive hepatic disease. Cardiac involvement is right-sided and characteristically spares the left heart, because the pulmonary vascular bed inactivates the remaining mediators before they reach the left side; the plaque-like deposits retract the tricuspid leaflets and produce regurgitation. The pellagra-like rash reflects diversion of tryptophan into serotonin synthesis at the expense of niacin. Diagnostically, urinary 5-HIAA is the mainstay but requires dietary restriction of serotonin-rich foods to avoid false positives, and chromogranin A supports it. Normal metanephrines and tryptase exclude pheochromocytoma and systemic mastocytosis, the two conditions most likely to be confused with this presentation. Treatment starts with a somatostatin analogue, octreotide or long-acting lanreotide, which controls the flushing and diarrhea in most patients and slows tumour progression as well. Bulky liver disease can be debulked or embolised, and peptide receptor radionuclide therapy is held back for progression. Two smaller points carry more weight in the short term. The low niacin needs replacing, since the tumour is consuming the tryptophan that would otherwise make it, and any surgery or anaesthesia has to be covered with octreotide, because handling the tumour can precipitate carcinoid crisis, a vasodilatory collapse far easier to prevent than to treat.

Key clinical clues

• Triad of episodic flushing, secretory diarrhea and wheeze, triggered by alcohol and food
• Right-sided valve disease sparing the left heart, mediators inactivated by the lungs
• Ileal primary with liver metastases; symptoms need hepatic disease to bypass portal clearance
• Pellagra-like rash from tryptophan diversion away from niacin synthesis
• Markedly raised urinary 5-HIAA with normal metanephrines and tryptase

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