What is the differential diagnosis for an adult patient with no significant medical history presenting with sudden onset constant epigastric fullness and decreased appetite for 10 days, which begins several hours after waking and is not associated with food intake?

Differential Diagnosis for Sudden Onset Constant Epigastric Fullness and Decreased Appetite

The most likely diagnosis is functional dyspepsia (postprandial distress syndrome subtype), but you must first exclude life-threatening causes including myocardial infarction, acute pancreatitis, perforated peptic ulcer, and gastric malignancy before making this diagnosis. 1

Immediate Life-Threatening Causes to Exclude First

• Myocardial infarction presenting atypically with isolated epigastric symptoms (10-20% mortality if missed), particularly in women, diabetics, and elderly patients—obtain ECG within 10 minutes and serial troponins at 0 and 6 hours 1, 2
• Acute pancreatitis characterized by epigastric pain radiating to back (though your patient lacks this radiation), diagnosed by serum lipase ≥2x normal or amylase ≥4x normal with 80-90% sensitivity and specificity 1
• Perforated peptic ulcer with 30% mortality if treatment delayed, identified by peritoneal signs (rigidity, rebound tenderness, absent bowel sounds) on physical examination 1
• Gastric outlet obstruction from malignancy, now the most common cause in adults due to decreased PUD incidence with widespread H2 blocker use 3

Most Likely Diagnosis: Functional Dyspepsia (Postprandial Distress Syndrome)

After excluding organic pathology, functional dyspepsia with postprandial distress syndrome is the primary diagnosis, as 80% of patients with dyspepsia will have functional dyspepsia after investigation. 1

Key Diagnostic Features Supporting This Diagnosis:

• Bothersome postprandial fullness (severe enough to impact usual activities) present at least 3 days per week, which is the cardinal symptom of postprandial distress syndrome 3
• Decreased appetite/early satiation preventing finishing regular-sized meals, the second defining feature of postprandial distress syndrome 3
• Symptom onset several hours after waking (not immediately meal-related) is consistent with functional dyspepsia, where symptoms may occur with or without direct food triggers 3
• 10-day duration meets the Rome IV clinical criteria requiring only 8 weeks of symptoms for routine clinical practice (less restrictive than research criteria requiring 6 months) 3

Alternative Functional Dyspepsia Subtype:

• Epigastric pain syndrome is less likely given the absence of bothersome epigastric pain or burning as the predominant symptom 3

Organic Causes Requiring Consideration

Gastroparesis or Delayed Gastric Emptying

• Gastroparesis presents with early satiety, postprandial fullness, nausea, and bloating—overlapping significantly with functional dyspepsia 4, 5
• Critical distinction: Gastroparesis and functional dyspepsia cannot be fully distinguished by symptoms alone and require gastric emptying studies (scintigraphy or breath testing) for definitive diagnosis 3, 5
• Pathophysiology: Delayed gastric emptying from antral hypomotility, impaired fundic accommodation, gastric dysrhythmias, or pylorospasm 4
• Note: The term "functional dyspepsia with delayed gastric emptying" may be preferable to gastroparesis, as the gastroparesis construct over-emphasizes motor deficits 3

Rapid Gastric Emptying

• Paradoxical cause: Epigastric fullness can result from rapid emptying leading to proximal small intestine distention, not just delayed emptying 6

Peptic Ulcer Disease

• Gastric or duodenal ulcer can present with epigastric fullness, though typically accompanied by epigastric pain or burning 3
• H. pylori infection is a major causative factor requiring testing via breath or stool antigen (not serology) 1, 2

Gastric Malignancy

• Age ≥55 years with early satiety/limited appetite qualifies as an alarm symptom requiring urgent 2-week wait endoscopy 7
• Gastric adenocarcinoma has 32% 5-year survival and often presents with nonspecific symptoms including early satiety and decreased appetite 3
• Your patient's age is critical: If ≥55 years, urgent endoscopy is mandatory; if <55 years without alarm features, empirical management is appropriate 1, 7

Gastritis or Gastric Inflammation

• Acute or chronic gastritis from H. pylori, NSAIDs, or other causes presents with epigastric fullness and decreased appetite 3
• CT findings: Gastric wall thickening, mucosal hyperenhancement, or fat stranding suggest gastritis 3

Gastroesophageal Reflux Disease (GERD)

• GERD affects 42% of Americans monthly and can present with epigastric fullness, though typically accompanied by heartburn or regurgitation 3
• Distinction: Burning sensation starting in epigastrium but radiating to chest suggests GERD over functional dyspepsia 1

Small Intestinal Disorders

• Celiac disease should be considered only if overlapping IBS-type symptoms (diarrhea, constipation, pain relieved by defecation) are present 7
• Small bowel obstruction (partial) can present with fullness and decreased appetite, though typically accompanied by cramping pain and distention 8

Diagnostic Algorithm

Step 1: Exclude Life-Threatening Causes

• ECG within 10 minutes to exclude myocardial infarction 1, 2
• Vital signs: Check for tachycardia ≥110 bpm, fever ≥38°C, or hypotension suggesting perforation or sepsis 1
• Physical examination: Assess for peritoneal signs (rigidity, rebound, absent bowel sounds) indicating perforation 1
• Serum lipase or amylase if any suspicion of pancreatitis 1

Step 2: Initial Laboratory Testing

• Complete blood count to assess for anemia (suggesting malignancy or chronic bleeding) and thrombocytosis (associated with gastroesophageal cancer) 1, 7
• C-reactive protein and serum lactate if concern for inflammatory or ischemic process 1
• Liver and renal function tests, serum electrolytes, and glucose 1, 2

Step 3: H. pylori Testing

• Test all patients using breath or stool antigen testing (not serology, which has lower specificity) as part of "test and treat" strategy, which ranks first in reducing symptoms at 12 months (RR 0.89; 95% CI 0.78-1.0) 1, 2

Step 4: Age-Based and Alarm Feature Assessment

If age ≥55 years OR any alarm features present:

• Urgent endoscopy (2-week wait if weight loss present; non-urgent if treatment-resistant dyspepsia or raised platelet count) 1, 7
• Alarm features: Weight loss, anemia, dysphagia, persistent vomiting, hematemesis, early satiety with limited appetite 1, 7

If age <55 years AND no alarm features:

• Proceed to empirical management without endoscopy initially 1

Step 5: Imaging if Diagnosis Unclear

• CT abdomen/pelvis with IV contrast is the gold standard when diagnosis remains unclear, identifying pancreatitis, perforation (extraluminal gas in 97%), gastric wall thickening, masses, or vascular emergencies 3, 1
• Use neutral oral contrast (water or dilute barium) to delineate intraluminal space when gastric disease suspected 3

Critical Pitfalls to Avoid

• Never dismiss cardiac causes regardless of age—atypical presentations are common, and missing MI has 10-20% mortality 1, 2
• Do not attribute persistent vomiting to functional dyspepsia—Rome IV criteria state this suggests another disorder and mandates investigation 3, 1
• Do not delay endoscopy in patients with alarm features (weight loss, anemia, dysphagia, age ≥55 years), as missing gastric cancer or perforated ulcer leads to poor outcomes 1, 7
• Clinical impression based on symptoms alone is unreliable and cannot distinguish functional disorders from severe conditions—objective testing is required 6
• Do not use H. pylori serology for test-and-treat strategy—use breath or stool testing only 1, 2