What causes vomiting, weight loss, and fatigue?

Differential Diagnosis of Vomiting, Weight Loss, and Fatigue

The combination of vomiting, weight loss, and fatigue requires urgent evaluation for life-threatening conditions including malignancy (particularly esophageal, gastric, and lung cancers), endocrine disorders (hyperthyroidism, adrenal insufficiency, hypopituitarism), and metabolic derangements, with the specific workup guided by associated symptoms, timing, and patient risk factors.

Critical Life-Threatening Causes to Exclude First

Malignancy

• Esophageal cancer commonly presents with this triad before diagnosis is established, with dysphagia, eating difficulties, and appetite loss resulting in considerable weight loss and fatigue that influence daily living 1
• Lung and gastrointestinal malignancies are leading causes of involuntary weight loss in adults, particularly when accompanied by constitutional symptoms 2
• Cancer-related symptoms including fatigue, anorexia, weight change, nausea, and vomiting are common toxic effects that influence nutrition 1

Endocrine Emergencies

• Hyperthyroidism can cause persistent vomiting, weight loss, and fatigue, with sinus tachycardia as a key diagnostic clue 3
• Adrenal insufficiency presents with fatigue, weight loss, nausea, and vomiting, and can progress to hypovolemic shock 1
• Hypopituitarism may present with chronic fatigue, malaise, weight loss, nausea, and vomiting that can be overlooked for years, particularly when hyponatremia is present 4

Metabolic and Infectious Causes

• Hepatic dysfunction and liver failure cause fatigue, altered mental status, and poor oral intake in patients with chronic alcohol use 5
• Systemic infections can present with fever, nausea, vomiting, diarrhea, fatigue, and weight loss 6

Essential Initial Assessment Components

History Elements That Guide Diagnosis

• Onset, pattern, duration, and changes over time help differentiate acute (≤7 days) from chronic (≥4 weeks) presentations 7
• Associated symptoms including dysphagia, odynophagia, abdominal pain, diarrhea, fever, or cough narrow the differential 1, 7
• Medication and substance use history, as polypharmacy and psychotropic medications commonly cause these symptoms 2
• Relationship to food intake and timing of symptoms distinguishes gastrointestinal from systemic causes 7

Physical Examination Priorities

• Vital signs including heart rate (tachycardia suggests hyperthyroidism or volume depletion) and temperature 3
• Mental status and cognitive function assessment, as hepatic encephalopathy, thiamine deficiency, and hypopituitarism cause overlapping neurological symptoms 5
• Muscle wasting and signs of malnutrition, particularly with poor oral intake 5
• Thyroid examination and signs of endocrine dysfunction 3

Algorithmic Diagnostic Approach

Immediate Laboratory Evaluation

• Complete blood count (anemia is common and contributes to fatigue) 1
• Comprehensive metabolic panel including electrolytes, renal function, and liver function 5, 2
• Ultrasensitive thyroid-stimulating hormone test to exclude thyroid disorders 2
• Fecal occult blood test if gastrointestinal symptoms present 2

Additional Testing Based on Clinical Suspicion

• Upper gastrointestinal studies have reasonably high yield in selected patients with dysphagia or persistent vomiting 2
• Chest radiograph if respiratory symptoms or smoking history present 6
• Abdominal imaging if hepatic dysfunction or abdominal pain present 6
• Brain imaging should be performed in patients with chronic liver disease and unexplained alteration of brain function to exclude structural lesions 5

Age-Specific Considerations

Elderly Patients

• Depression is the leading cause of unintentional weight loss, especially in long-term care facility residents 2
• Approximately one quarter of elderly patients with unintentional weight loss have no identifiable cause after thorough evaluation 2
• Polypharmacy and medication interactions more commonly contribute to symptoms 2

Younger Adults

• Early pregnancy must be excluded in women of childbearing age 7
• Inflammatory bowel disease should be considered with chronic diarrhea 1
• Eating disorders and psychiatric conditions require screening 1

Critical Pitfalls to Avoid

• Never assume fatigue is solely due to one cause, as multiple organ systems may be simultaneously affected, particularly in patients with chronic alcohol use or malignancy 5
• Do not overlook endocrine causes when gastrointestinal symptoms dominate the presentation, as hyperthyroidism and hypopituitarism can present primarily with vomiting 4, 3
• Normal ammonia levels do not exclude hepatic encephalopathy in patients with liver disease 5
• Failing to assess nutritional status and implement early nutritional support when oral intake is inadequate 8
• Overlooking medication-induced symptoms, as combinations of narcotics, antidepressants, antiemetics, and antihistamines contribute to excessive drowsiness and fatigue 1

Immediate Management Priorities

Supportive Care

• Fluid and electrolyte replacement for patients with vomiting 1
• Administer IV thiamine before any glucose-containing solutions in patients with alcohol use disorder to prevent Wernicke encephalopathy 5
• Small, frequent meals and avoidance of trigger foods 1

Symptom Control

• Serotonin antagonists or dopamine antagonists effectively reduce acute nausea and vomiting when specific etiology is not immediately identified 7
• Antiemetic drugs should be used for the shortest time necessary to control symptoms 7

Nutritional Support

• Oral nutritional supplements should be considered if poor appetite persists beyond 5-7 days 8
• Enteral nutrition should be initiated if oral intake remains less than 50% of requirements for more than 7 days 8

When to Escalate Care

• Alarm symptoms including severe abdominal pain, blood in stool or vomit, severe headache, confusion, or respiratory distress require urgent evaluation 1
• Progressive weight loss exceeding 10% of body weight warrants expedited workup for malignancy 1
• Failure to improve with initial management indicates need for additional evaluation and specialist referral 5