Workup for Unexplained Weight Loss
The appropriate workup for unexplained weight loss should include a comprehensive metabolic panel, complete blood count, thyroid function tests, fasting glucose/HbA1c, inflammatory markers, urinalysis, chest radiography, and fecal occult blood testing as initial investigations. 1
Initial Assessment
History
- Quantify weight loss (amount, timeframe)
- Dietary changes and appetite
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Psychological symptoms (depression, anxiety)
- Medication review (those affecting taste or causing nausea)
- Social factors (food insecurity, isolation)
- Review of systems for malignancy symptoms (night sweats, fatigue)
Physical Examination
- Vital signs including temperature
- Comprehensive examination focusing on:
- Oral cavity (dentition, mucositis)
- Thyroid
- Lymph nodes
- Abdominal examination
- Rectal examination
Laboratory Investigations
First-line Tests
- Complete blood count
- Basic metabolic panel
- Liver function tests
- Thyroid function tests (TSH)
- C-reactive protein and erythrocyte sedimentation rate
- Fasting glucose or HbA1c
- Urinalysis
- Fecal occult blood test 1
Imaging
- Chest radiography (required in initial evaluation)
- Abdominal ultrasonography 1
Additional Investigations Based on Initial Findings
For Suspected Gastrointestinal Causes
- Upper endoscopy and colonoscopy (particularly important as GI causes account for approximately 30% of unexplained weight loss) 2
- Tests for malabsorption if clinically indicated
For Suspected Malignancy
- Age-appropriate cancer screenings
- Consider whole-body CT for patients with additional concerning symptoms, abnormal physical examinations, anemia, or elevated tumor markers (diagnostic yield of 33.5%) 3
For Suspected Endocrine Causes
- Additional thyroid studies
- Consider screening for Cushing syndrome if clinically suspected 4
For Suspected Psychiatric Causes
- Depression screening (psychological disorders represent approximately 11% of non-malignant causes of weight loss) 2
Diagnostic Approach Algorithm
- Perform initial laboratory and imaging studies
- If initial evaluation is unremarkable:
- Consider GI endoscopic evaluation
- Consider psychiatric evaluation
- Consider observation for 3-6 months with regular weight monitoring 1
- If diagnosis remains unclear after comprehensive evaluation (occurs in 16-28% of cases), continue monitoring as prognosis for unknown causes is similar to non-malignant causes 1, 2
Important Considerations
- Non-malignant diseases are more common causes of unexplained weight loss than malignancy in older adults 1
- Gastrointestinal disorders account for weight loss in approximately one-third of patients 2
- Medication use and polypharmacy should be carefully evaluated 1
- When baseline evaluation is unremarkable, a 3-6 month observation period is appropriate 1
- Psychological disorders, particularly depression, may account for up to 60% of cases in some studies 5
Remember that a cause is not identified in 16-28% of cases despite thorough evaluation 1. Treatment should focus on the underlying cause when identified, with consideration of nutritional support during the diagnostic process.