Carcinoid syndrome
Carcinoid syndrome is the clinical syndrome of episodic flushing, secretory diarrhea, and late right-sided valvular heart disease caused by serotonin and other vasoactive amines escaping hepatic first-pass metabolism, almost always because a well-differentiated neuroendocrine tumor has spread to the liver or arises outside the portal circulation. Diagnosis rests on an elevated 24-hour urinary 5-HIAA with tumor localization by somatostatin-receptor PET, and management combines somatostatin analogues for symptom control and antiproliferative effect with tumor-directed therapy and peri-procedural crisis prevention.
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What this article covers
- Overview
Definition: carcinoid syndrome is the clinical syndrome produced when a well-differentiated neuroendocrine tumor secretes serotonin and other vasoactive amines directly into the systemic circulation…
- Epidemiology
Rare presentation of an uncommon tumor: carcinoid syndrome develops in only a minority, roughly one third to one half, of patients with metastatic gastrointestinal neuroendocrine tumors, because most such tumors are hormonally nonfunctional.
- Risk factors
Hepatic metastasis from a midgut neuroendocrine tumor: the dominant risk factor, because it removes the liver's first-pass clearance of secreted mediators.
- Pathophysiology
Serotonin synthesis diverts tryptophan: the tumor converts dietary tryptophan to serotonin instead of niacin, which drives both the peripheral effects of the syndrome and, when sustained, niacin deficiency.
- Clinical features
Episodic flushing: the most common feature, typically affecting the face, neck, and upper trunk, lasting seconds to a few minutes, sometimes provoked by alcohol, stress, or certain foods.
- Differential diagnosis
Pheochromocytoma: episodic flushing can occur, but the dominant pattern is paroxysmal hypertension with headache and diaphoresis rather than diarrhea, distinguished by elevated plasma or urinary metanephrines (Pheochromocytoma).
- Diagnosis
Establish the diagnosis with an elevated 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA): the biochemical confirmatory test, reflecting excess systemic serotonin turnover from a functioning…
- Management
Start a somatostatin analogue as first-line therapy for symptom control: it both relieves flushing and diarrhea and slows tumor growth.
- Complications
Carcinoid heart disease and right heart failure: progressive tricuspid and pulmonary valve fibrosis leads to regurgitation, volume overload, and right-sided heart failure; a major determinant of morbidity and mortality once established.
- Prognosis
Driven by tumor biology and hepatic burden more than the syndrome itself: overall survival correlates with tumor grade, hepatic metastatic burden, and completeness of source control, detailed under well-differentiated neuroendocrine tumors.
- Prevention
Peri-procedural octreotide prophylaxis in every known case: octreotide 500 mcg SC or IV 1 hour before any surgery, anesthesia, endoscopy with biopsy, or embolization, with an infusion available intraoperatively.
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Related articles
- Well-differentiated neuroendocrine tumors
Well-differentiated neuroendocrine tumors (formerly carcinoid tumors) arise from enterochromaffin and islet-type cells of the gut and pancreas, are graded G1 to G3 by Ki-67 and mitotic count, and may be functional (gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma, or carcinoid syndrome) or nonfunctional. Diagnosis rests on biopsy with neuroendocrine markers plus Ki-67 grading and somatostatin-receptor imaging, and management ranges from surgical resection to somatostatin analogues, peptide receptor radionuclide therapy, and targeted agents.
- Pancreatic neuroendocrine tumors (PanNETs)
Pancreatic neuroendocrine tumors (PanNETs) are islet-cell tumors that may be functional, producing a hormone-excess syndrome such as insulinoma or gastrinoma, or nonfunctioning and detected by mass effect or incidentally. First-line treatment is surgical resection when localized, with somatostatin analogues and acid suppression used to control hormone-excess symptoms before or in place of surgery.
- Hyperthyroidism
Hyperthyroidism is the clinical syndrome of thyroid hormone excess, produced by a range of causes from Graves disease and autonomously functioning nodules to destructive thyroiditis and exogenous hormone ingestion. Diagnosis begins with a suppressed thyroid-stimulating hormone and elevated free thyroxine, followed by radioactive iodine uptake testing or antibody measurement to identify the cause, and first-line treatment is a beta blocker for symptom control while the underlying cause directs thionamide, radioactive iodine ablation, or thyroidectomy therapy.
- Pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma are catecholamine-secreting tumors of adrenal medullary chromaffin cells and extra-adrenal sympathetic ganglia, causing sustained or paroxysmal hypertension with headache, sweating, and palpitations, diagnosed by plasma free or 24-hour urine fractionated metanephrines before any imaging is obtained. First-line treatment is surgical resection preceded by alpha blockade with phenoxybenzamine (or off-label doxazosin) for 10 to 14 days, with a beta blocker added only after alpha blockade is established.
- Diarrhea
Diarrhea is three or more unformed stools daily, split by duration into acute (under 14 days, usually infectious), persistent (14 to 30 days, often parasitic), and chronic (over 30 days, usually noninfectious), and by mechanism into osmotic, secretory, inflammatory, malabsorptive, and motility diarrhea. Acute diarrhea is managed with rehydration and tested only when red-flag features are present, while chronic diarrhea is worked up by mechanism using stool studies, celiac serology, fecal calprotectin, and endoscopy.