What is the appropriate diagnostic work‑up for an adult with chronic nausea and vomiting lasting ≥4 weeks?

Diagnostic Work-Up for Chronic Nausea and Vomiting in Adults

Begin with a detailed history to differentiate vomiting from regurgitation, rumination, or bulimia, followed by gastric emptying scintigraphy (4-hour protocol) as the gold standard test to confirm or exclude gastroparesis, and upper endoscopy to rule out structural obstruction. 1

Initial Clinical Assessment

The evaluation starts with characterizing the symptom pattern and identifying red flags:

• Differentiate the symptom: Distinguish true vomiting from regurgitation (effortless return of food), rumination (voluntary regurgitation and rechewing), or self-induced vomiting in bulimia 1
• Duration and frequency: Document how long symptoms have persisted (≥4 weeks defines chronic), how often vomiting occurs, and the severity of episodes 1
• Timing patterns: Note whether symptoms are postprandial, nocturnal, or related to specific foods 1
• Associated symptoms: Ask specifically about early satiety, postprandial fullness, bloating, abdominal pain, and weight loss 1

Physical Examination Findings to Assess

The physical examination should target specific findings that guide diagnosis:

• Succussion splash: Indicates delayed gastric emptying or gastric outlet obstruction 1
• Right upper quadrant bruit on auscultation: Suggests celiac artery compression syndrome 1
• Digital ulcers and telangiectasia: Point toward scleroderma as an underlying cause 1
• Ascites, abdominal mass, or enlarged lymph nodes: Raise concern for underlying malignancy 1
• Signs of dehydration or malnutrition: Assess for consequences of chronic vomiting 1

Mandatory Diagnostic Testing

First-Line Test: Gastric Emptying Scintigraphy

Gastric emptying scintigraphy with a radiolabeled solid meal is the best accepted method to diagnose gastroparesis. 1

• Protocol specifics: The test must be performed for 4 hours (not 2 hours) after ingestion to maximize diagnostic yield in symptomatic patients 1
• Technical requirements: The radioisotope must be cooked into the solid portion of the meal, not just mixed in 1
• Interpretation: Shorter test durations are inaccurate and should not be used 1

Rule Out Structural Obstruction

Upper endoscopy (esophagogastroduodenoscopy) is essential to exclude mechanical obstruction in the stomach or small intestine before diagnosing gastroparesis. 1

• The diagnosis of gastroparesis requires both delayed gastric emptying AND absence of obstructing structural lesions 1
• Endoscopy can identify peptic ulcer disease, malignancy, or other anatomic causes of symptoms 1

Additional Laboratory Work-Up

If not recently performed, obtain:

• Complete blood count: To assess for anemia or infection 1
• Liver chemistries: To evaluate hepatobiliary causes 1
• Metabolic panel: To check electrolytes (especially in patients with frequent vomiting) and glucose control in diabetics 1
• Thyroid function tests: Hypothyroidism and hyperthyroidism can cause dysmotility 1

Specialized Testing for Refractory Cases

Antroduodenal Manometry

• Provides information about coordination of gastric and duodenal motor function in fasting and postprandial periods 1
• Shows decreased antral contractility and abnormal migrating motor complexes in gastroparesis 1
• Reserved for cases where diagnosis remains unclear after standard testing 1

Alternative Gastric Emptying Tests

• 13C-octanoate breath test: Uses nonradioactive isotope to measure gastric emptying indirectly, but primarily used in research settings rather than routine clinical practice 1

Critical Diagnostic Pitfalls to Avoid

• Do not diagnose gastroparesis without objective confirmation: Symptoms alone are insufficient; delayed gastric emptying must be documented 1
• Do not skip endoscopy: Structural obstruction must be excluded before attributing symptoms to a motility disorder 1
• Do not use 2-hour gastric emptying studies: The 4-hour protocol significantly increases diagnostic yield 1
• Do not overlook medication-induced causes: Opioids and GLP-1 agonists commonly cause gastroparesis-like symptoms and must be identified before extensive testing 1
• Do not miss underlying systemic diseases: Diabetes, scleroderma, and other connective tissue disorders are common causes that require specific evaluation 1

Differential Diagnosis Considerations

The differential diagnosis of chronic nausea and vomiting is extensive and includes:

• Gastrointestinal causes: Gastroparesis, functional dyspepsia, peptic ulcer disease, gastric outlet obstruction, chronic intestinal pseudo-obstruction 1
• Central nervous system causes: Increased intracranial pressure, vestibular disorders, cyclic vomiting syndrome 1
• Endocrine/metabolic causes: Diabetic ketoacidosis, hyperthyroidism, hypothyroidism, adrenal insufficiency, uremia 1
• Medication-related: Opioids, GLP-1 agonists, chemotherapy agents 1