How can I differentiate between carcinoid syndrome and other causes of flushing and diarrhea in a patient?

To differentiate carcinoid syndrome from other causes of flushing and diarrhea, focus on the clinical features, biochemical testing, and exclusion of alternative diagnoses. Carcinoid syndrome typically presents with episodic flushing, secretory diarrhea, bronchospasm, and sometimes right-sided cardiac valvular lesions due to serotonin and other vasoactive substances released by neuroendocrine tumours (NETs) ¹ (Gade et al., 2020). The flushing in carcinoid syndrome is often described as a rapid onset, pink to red flushing involving the face and upper chest, sometimes accompanied by a burning sensation, which contrasts with the more prolonged or patchy flushing seen in other conditions such as mast cell disorders or menopausal flushing ¹ (Rastogi et al., 2018).

Biochemical differentiation is key: Measure 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, which is elevated in carcinoid syndrome but normal in most other causes of flushing and diarrhea ¹ (Lips et al., 2003). Plasma chromogranin A can also support the diagnosis but is less specific ¹ (Gade et al., 2020). Other causes such as mast cell activation syndrome may show elevated serum tryptase or histamine levels, which are not elevated in carcinoid syndrome (Rastogi et al., 2018).

Imaging and clinical context: Identification of a primary NET or metastatic disease on imaging (CT, MRI, or somatostatin receptor scintigraphy) supports carcinoid syndrome diagnosis ¹ (Lips et al., 2003). In contrast, flushing and diarrhea due to other causes like menopausal symptoms, medication side effects, or inflammatory bowel disease lack these tumour markers and imaging findings ¹.

Summary: The combination of characteristic episodic flushing and secretory diarrhea, elevated urinary 5-HIAA, and evidence of NET on imaging differentiates carcinoid syndrome from other causes of flushing and diarrhea. Alternative diagnoses should be considered if these features are absent, and appropriate tests for mast cell disorders or other etiologies should be pursued ¹ (Rastogi et al., 2018; Gade et al., 2020).