What is the appropriate workup and differential diagnosis for a 21-year-old female with 3 weeks of persistent nausea and vomiting?

Workup and Differential Diagnosis for 21-Year-Old Female with 3 Weeks of Persistent Nausea and Vomiting

Obtain a urine pregnancy test immediately—pregnancy is the most common cause of persistent nausea and vomiting in reproductive-age females and must be ruled out first. 1

Initial Laboratory Workup

The following tests should be ordered systematically to identify the underlying cause:

• Urine pregnancy test (β-hCG): Mandatory first step in any reproductive-age female with nausea and vomiting 1, 2
• Complete blood count (CBC): Assess for infection, anemia, or hematologic abnormalities 1
• Comprehensive metabolic panel: Identify metabolic causes including hypercalcemia, uremia, hyponatremia, hyperglycemia, or Addison's disease 1
• Liver function tests and lipase: Exclude hepatobiliary disease, pancreatitis 1
• Thyroid-stimulating hormone (TSH): Rule out hyperthyroidism or hypothyroidism 3
• Urinalysis: Assess for urinary tract infection or diabetic ketoacidosis 1
• Urine drug screen: Specifically test for cannabis, as Cannabis Hyperemesis Syndrome (CHS) is increasingly common in this age group 1

Differential Diagnosis by Category

Gastrointestinal Causes

• Gastroparesis/delayed gastric emptying: Symptoms worsen throughout the day as food accumulates; consider if symptoms have evening predominance 4, 5
• Gastroesophageal reflux disease (GERD): Patients often cannot distinguish heartburn from nausea 5
• Peptic ulcer disease or gastritis: Consider if pain is present 2, 3
• Functional dyspepsia: Present in approximately 20% of the general population, with 25-40% having delayed gastric emptying 4
• Bowel obstruction: Evaluate if bilious vomiting or abdominal distension present 4, 2
• Inflammatory bowel disease: Consider if diarrhea or weight loss present 2

Pregnancy-Related

• Early pregnancy/hyperemesis gravidarum: Most common cause in this demographic; symptoms typically begin 4-9 weeks gestation 1, 6

Medication/Toxin-Related

• Cannabis Hyperemesis Syndrome: Requires detailed substance use history; patients often report relief with hot showers 1
• Medication side effects: Review all medications including SSRIs, NSAIDs, antibiotics, opioids 2, 3

Metabolic/Endocrine

• Diabetic ketoacidosis: Check glucose and ketones if diabetic or hyperglycemic 1
• Hypercalcemia: Can cause nausea independent of other symptoms 1
• Uremia/renal failure: Check creatinine and BUN 1
• Adrenal insufficiency: Consider if hypotension or electrolyte abnormalities present 2
• Hyperthyroidism: Check TSH 3

Central Nervous System

• Increased intracranial pressure: From tumor, trauma, or idiopathic intracranial hypertension; look for headache, visual changes, neurologic signs 4, 2
• Migraine-associated nausea: Often cyclical pattern 2, 3
• Vestibular disorders: Associated with vertigo or dizziness 2

Infectious

• Chronic gastroenteritis: Consider parasitic infections (Giardia) if travel history or persistent diarrhea 2, 7
• Hepatitis: Check liver enzymes 3
• Urinary tract infection/pyelonephritis: Check urinalysis 1

Psychiatric

• Anxiety disorders: Can manifest as chronic nausea 3, 7
• Eating disorders (bulimia): Requires sensitive questioning about eating behaviors 4, 2
• Cyclic vomiting syndrome: Episodic pattern with symptom-free intervals 2

Key Historical Features to Elicit

• Timing and pattern: Morning symptoms suggest pregnancy; evening symptoms suggest gastroparesis 1, 5
• Relationship to meals: Postprandial fullness suggests gastroparesis or functional dyspepsia 4
• Vomitus characteristics: Bilious suggests obstruction distal to ampulla of Vater; undigested food suggests gastroparesis 4
• Cannabis use: Specifically ask about frequency and recent changes in use 1
• Hot shower relief: Pathognomonic for Cannabis Hyperemesis Syndrome 1
• Weight loss: Suggests organic pathology requiring urgent evaluation 2, 7
• Medication history: Recent additions or dose changes 2, 3
• Sexual activity and contraception use: Essential for pregnancy risk assessment 1

Advanced Testing (If Initial Workup Negative)

• Gastric emptying scintigraphy: Gold standard for gastroparesis diagnosis; must be performed for at least 2 hours (preferably 4 hours) with radiolabeled solid meal 4, 5
• Upper endoscopy (EGD): Indicated if alarm symptoms present (weight loss, dysphagia, anemia, age >50) or if gastric malignancy risk factors exist 3, 7
• Abdominal imaging (CT or ultrasound): If obstruction, mass, or hepatobiliary disease suspected 3, 8
• Head CT/MRI: Only if neurologic signs or symptoms of increased intracranial pressure present 4, 8

Critical Pitfalls to Avoid

• Never overlook pregnancy testing in any reproductive-age female with nausea and vomiting, regardless of reported sexual history 1
• Do not use antiemetics if mechanical bowel obstruction is suspected, as this masks progressive ileus and gastric distension 1
• Do not perform repeated endoscopy or imaging unless new alarm symptoms develop 1
• Cannabis use requires direct, non-judgmental questioning; patients may not volunteer this information 1
• Three weeks duration makes simple viral gastroenteritis unlikely; chronic causes must be systematically evaluated 2, 7