What is the differential diagnosis for a 15-year-old male with no prior medical history, presenting with morning nausea and vomiting, mild abdominal cramping, and abdominal tenderness, but no headaches, constipation, or diarrhea, and normal laboratory results, including complete blood count (CBC), comprehensive metabolic panel (CMP), iron, ferritin, thyroid-stimulating hormone (TSH), and vitamin D levels?

Differential Diagnosis for Morning Nausea and Vomiting in a 15-Year-Old Male

The most likely diagnosis in this adolescent with isolated morning nausea, vomiting, and abdominal cramping is cyclic vomiting syndrome (CVS), followed by cannabinoid hyperemesis syndrome (CHS) despite the negative urine drug screen, functional dyspepsia with gastroparesis features, and less likely but critical to exclude—superior mesenteric artery syndrome or other mechanical causes.

Primary Differential Diagnoses

Cyclic Vomiting Syndrome (Most Likely)

• CVS has a prevalence of approximately 2% in US adults and characteristically presents with stereotypical episodes of acute-onset vomiting that can occur at specific times of day, most commonly in the early morning hours 1, 2
• The morning-predominant pattern strongly suggests CVS, as most episodes tend to occur in early morning hours 1
• Abdominal pain is present in most patients during CVS episodes and should not preclude this diagnosis 1
• Prodromal symptoms lasting approximately 1 hour before vomiting onset occur in 65% of CVS patients, which may manifest as the mild cramping described 1
• Constitutional symptoms including fatigue, feeling hot or cold, mental fog, restlessness, anxiety, bowel urgency, diaphoresis, or shakiness are common during prodromal and emetic phases 1
• Psychiatric comorbidity, younger age, and tobacco use are associated with CVS 2

Cannabinoid Hyperemesis Syndrome (Critical to Reconsider)

• Cannabis use has a pooled prevalence of 47% in patients with CVS-like symptoms, and CHS is characterized by paradoxical cannabis-associated vomiting with patients reporting need for hot water bathing to alleviate symptoms 2
• A negative urine drug screen does NOT exclude CHS—you must obtain a detailed cannabis use history directly, as patients may not volunteer this information and urine screens can be falsely negative depending on timing and sensitivity 2
• Missing cannabis use history is a critical pitfall, as cannabis use augments hot water bathing behavior and distinguishes CHS from CVS 2
• Cannabinoid withdrawal syndrome (CWS) occurs commonly on cessation of heavy and prolonged cannabis use and can present with morning nausea 2

Functional Dyspepsia with Gastroparesis Features

• Morning nausea with abdominal cramping fits the pattern of functional dyspepsia, which is defined by Rome IV criteria as bothersome epigastric pain, burning, postprandial fullness, or early satiation without structural disease 1, 2
• Delayed gastric emptying occurs in 25-40% of functional dyspepsia patients and is more frequent in patients with nausea and vomiting 1, 2
• However, when vomiting is prominent or persistent in functional dyspepsia, this likely represents the gastroparesis end of the spectrum and warrants gastric emptying scintigraphy 2
• The morning-only pattern is somewhat atypical for pure gastroparesis, which usually causes symptoms throughout the day 1

Superior Mesenteric Artery Syndrome (Must Exclude)

• This mechanical cause presents with nausea, vomiting, and abdominal pain, particularly in thin adolescents 1
• Can be evaluated with radiologic imaging such as small bowel follow-through or CT enterography 1
• The abdominal tenderness on exam makes this diagnosis important to exclude 1

Essential Diagnostic Workup

Immediate Next Steps

• Obtain detailed cannabis use history directly—ask specifically about frequency, duration, and any hot water bathing behaviors for symptom relief 2
• Ask about triggers including stress (70-80% of CVS patients), sleep deprivation, hormonal fluctuations, travel, motion sickness, infections, surgery, fasting, or intense exercise 1
• Inquire about prodromal symptoms: impending sense of doom, panic, inability to communicate, fatigue, mental fog, restlessness, anxiety, headache, bowel urgency, diaphoresis, flushing, or shakiness occurring before vomiting episodes 1
• Document the stereotypical nature of episodes—CVS patients can identify a specific order of onset and cluster of symptoms that recur with each episode 1

Required Testing

• Upper endoscopy is essential to exclude mechanical obstruction, peptic ulcer disease, and malignancy before diagnosing a functional or motility disorder 2, 3
• If upper endoscopy is normal and vomiting persists, perform gastric emptying scintigraphy for at least 4 hours (gold standard for gastroparesis diagnosis) 2, 3
• Normal gastric retention at 4 hours is <10%; gastroparesis is confirmed when retention is >10% at 4 hours 2
• Medications affecting gastric emptying should be withdrawn 48-72 hours prior to testing, and blood glucose should be maintained in normal range during the test 2

Additional Considerations

• Check serum amylase or lipase to exclude acute pancreatitis (≥2x normal for lipase, ≥4x normal for amylase) 3
• Obtain ECG and serial cardiac troponins at 0 and 6 hours to exclude atypical presentation of myocardial infarction, even in this young patient if risk factors present 3
• Consider CT or ultrasound imaging if superior mesenteric artery syndrome or other mechanical obstruction is suspected based on body habitus or exam findings 1

Critical Pitfalls to Avoid

• Never attribute persistent vomiting to functional dyspepsia alone—Rome IV criteria state this suggests another disorder and mandates investigation for structural disease 3
• Do not rely on negative urine drug screen to exclude cannabis use—obtain detailed direct history about cannabis, as screens can be falsely negative 2
• Relying solely on symptoms can be misleading, as symptoms correlate poorly with degree of gastric emptying delay 2
• Shorter gastric emptying test durations (<2 hours) are inaccurate for determining gastroparesis 2
• Not accounting for medications affecting gastric emptying (prokinetics, opioids, anticholinergics) can lead to inaccurate results 2

Management Approach Pending Workup

• If CVS is suspected, educate the patient about recognizing prodromal symptoms and triggers, as early intervention during the prodromal phase has higher probability of aborting episodes 1
• Start empirical high-dose PPI therapy (omeprazole 20-40 mg once daily before meals) while awaiting endoscopy to address potential acid-related pathology 3
• Provide antiemetic agents such as phenothiazines or 5-HT3 receptor antagonists for symptomatic relief 4
• Avoid opioids as they worsen gastric emptying and symptoms 2, 4
• Recommend dietary modifications including frequent smaller meals, replacing solid food with liquids when symptomatic, and maintaining adequate hydration 4