What is the differential diagnosis for a patient presenting with cough, palpitations, episodes of flushing, and tachycardia?

Differential Diagnosis: Cough, Palpitations, Flushing, and Tachycardia

The combination of cough, palpitations, flushing episodes, and tachycardia should immediately raise suspicion for carcinoid syndrome, systemic mastocytosis, or pheochromocytoma—all potentially life-threatening neuroendocrine conditions that require urgent biochemical evaluation before considering more benign causes.

Critical Life-Threatening Diagnoses to Exclude First

Carcinoid Syndrome

• Carcinoid syndrome classically presents with episodic flushing, tachycardia, and right-sided valvular heart disease 1
• The presence of excessive 5-HIAA in 24-hour urine collection and response to somatostatin analogs strongly supports this diagnosis 1
• Right-sided heart valve disease (tricuspid regurgitation, pulmonary stenosis) distinguishes carcinoid from other flushing syndromes 1
• Order: 24-hour urine 5-HIAA, serum chromogranin A, and CT chest/abdomen to locate primary tumor 2

Systemic Mastocytosis

• Mastocytosis presents with flushing, tachycardia, and potential anaphylactic episodes 1
• Look for characteristic skin lesions (urticaria pigmentosa) and obtain serum tryptase levels 1
• Bone marrow biopsy with immunohistochemistry provides definitive diagnosis showing increased mast cell infiltration 1
• Absolute mast cell counts in skin biopsies are less diagnostically helpful 1

Pheochromocytoma

• Episodic hypertension with tachycardia, palpitations, and flushing suggests catecholamine excess 2
• Obtain 24-hour urine metanephrines and plasma free metanephrines 2
• CT or MRI of adrenals once biochemical diagnosis confirmed 2

Secondary Considerations After Excluding Neuroendocrine Causes

Pertussis Infection (Bordetella pertussis)

• Pertussis causes prolonged paroxysmal cough lasting 4-6 weeks or longer, often called "the hundred day cough" 3
• The paroxysmal phase features spasmodic cough with posttussive vomiting; the classic "whoop" is frequently absent in adults 3
• Tachycardia occurs during coughing paroxysms but does not explain isolated flushing episodes 3
• Diagnosis requires PCR or culture during catarrhal phase (first 2 weeks); serologic testing for IgG/IgA antibodies if presenting later 3
• This diagnosis becomes less likely if flushing occurs independent of cough episodes

Supraventricular Tachycardia (SVT)

• Regular paroxysmal palpitations with abrupt onset and termination suggest AVNRT or AVRT 3
• Patients describe sudden episodes of rapid regular heartbeat, sometimes with polyuria after termination 3
• Obtain 12-lead ECG during tachycardia; look for pseudo-R wave in V1 or pseudo-S waves in inferior leads suggesting AVNRT 3
• SVT alone does not explain cough or flushing, making this an incomplete diagnosis for the full symptom complex 3

Upper Airway Cough Syndrome (UACS)

• UACS can cause chronic cough with sensation of postnasal drip, though "silent" UACS exists without typical symptoms 3
• Trial of first-generation antihistamine plus decongestant for 1-2 weeks is diagnostic and therapeutic 3
• Does not explain palpitations, tachycardia, or flushing episodes 3

Gastroesophageal Reflux Disease (GERD)

• GERD causes chronic cough and can mimic upper airway symptoms 3, 4
• Empiric proton pump inhibitor therapy for 8-12 weeks is appropriate if reflux symptoms present 4
• Does not account for flushing or palpitations 3

Diagnostic Algorithm

Step 1: Immediate biochemical screening (same day)

• 24-hour urine 5-HIAA (carcinoid) 1
• Serum tryptase (mastocytosis) 1
• 24-hour urine or plasma metanephrines (pheochromocytoma) 2
• Serum chromogranin A 2

Step 2: If biochemical tests negative, obtain 12-lead ECG

• Capture rhythm during palpitations if possible 3
• Look for pre-excitation (delta waves) suggesting accessory pathway 3

Step 3: Chest radiograph

• Evaluate for pulmonary pathology, carcinoid tumor, or infiltrates 4

Step 4: If above unrevealing, consider infectious causes

• Pertussis PCR/culture if cough duration >2 weeks with paroxysmal character 3
• Pertussis serology if >4 weeks from symptom onset 3

Step 5: Empiric trials only after excluding dangerous causes

• First-generation antihistamine/decongestant for UACS 3
• PPI therapy for suspected GERD 4

Critical Pitfalls to Avoid

• Never dismiss flushing as benign rosacea or menopause without excluding carcinoid and mastocytosis 1, 2
• Do not attribute tachycardia solely to anxiety when combined with flushing and cough 5
• Avoid treating isolated symptoms (antitussives for cough, beta-blockers for tachycardia) before establishing underlying diagnosis 3
• If patient is on ACE inhibitor, discontinue immediately as this causes chronic cough in up to 20% of patients; resolution typically occurs within 1-4 weeks 3, 4
• Do not assume SVT explains all symptoms—the combination with flushing demands broader investigation 3