Work-up for unintentional weight loss

1. Confirm the weight loss is real and significant

• Significant loss is more than 5% of usual body weight over 6-12 months. Loss above 10% is severe and suggests protein-energy malnutrition. (Symptom to Diagnosis: An Evidence Based Guide, 4th ed.; Sleisenger and Fordtran's Gastrointestinal and Liver Disease)
• Document it with old weights, or with changes in clothing or belt size. Family or caregiver history helps.
• 25-50% of people who complain of weight loss haven't actually lost weight. Older adults often lose muscle mass and just look thinner. (Symptom to Diagnosis)
• Patient estimates can mislead. Among patients who overestimated their loss, cancer was found in only 6%. Among those who underestimated it, cancer was found in 52%. (Symptom to Diagnosis)
• History alone is imperfect. One study found that a third of patients with true loss were missed by history. (Sleisenger and Fordtran's)

2. Think through the mechanism

• Stool changes. Diarrhea or greasy, foul-smelling stools suggest malabsorption, small bowel disease or pancreatic disease. Narrow stools or difficulty defecating suggest colorectal cancer.
• Intake versus expenditure.
  • Most patients lose weight because they eat less. Causes include depression, dental problems, dysphagia, early satiety, dementia, medications, alcohol and social isolation.
  • Loss despite normal or high intake points to a hypermetabolic or catabolic state, or to malabsorption. Think of cancer, hyperthyroidism, uncontrolled diabetes, severe COPD, chronic infection and malabsorption.

3. History and examination

• Review of systems: fever, night sweats, cough, hemoptysis, dysphagia, abdominal pain, bowel changes, GI bleeding, polyuria, palpitations.
• Medication history: SGLT2 inhibitors, GLP-1 agonists, metformin, diuretics, digoxin, SSRIs, stimulants, chemotherapy.
• Substances and exposures: alcohol, tobacco, drugs, TB or HIV risk, travel.
• Psychosocial: mood (PHQ-2 or PHQ-9), cognition, eating disorder, finances, ability to shop and cook, dentition.
• Examination:
  • Full head-to-toe exam, with attention to mental status.
  • Oral and dental exam, thyroid, lymph nodes, breast, abdomen (masses, organomegaly), rectal exam, skin, and neurologic and joint findings.
  • Check that cancer screening is up to date (mammogram, Pap/HPV, colonoscopy, PSA where appropriate).

4. Baseline investigations

• CBC with differential
• Chemistry panel: renal function, calcium, glucose
• Liver panel
• TSH
• ESR and CRP
• Urinalysis
• Fecal occult blood test
• HIV test where appropriate
• Chest X-ray
• Abdominal ultrasound, which several studies added

• Ferritin, B12, folate and celiac serology if malabsorption is suspected.
• Stool studies and fecal elastase.
• HbA1c.
• Cortisol if adrenal insufficiency is suspected.
• Blood cultures, TB testing and ANA/ANCA if infection or autoimmune disease is suspected.
• SPEP if myeloma is suspected.

5. Targeted follow-up of abnormal findings

6. Common causes

• Cancer: about 19-36%. It is mostly GI, then lung and lymphoma.
• Depression and alcoholism: about 16%.
• Non-malignant GI disease: about 13%.
• Endocrine disease: about 7%.
• No cause found: about 22%.

7. If the work-up is negative

• Cancer is unlikely after a negative initial evaluation with appropriate follow-up of any abnormalities.
• Don't keep ordering tests. Reassess in 1-3 months with serial weights and repeat the history.
• Offer nutritional support, dietitian input and treatment of any contributors. Artificial nutrition mainly helps patients with a reversible mechanical cause of poor intake. Examples are head and neck cancer after radiotherapy, bowel obstruction, and upper GI surgery.
• Revisit the work-up if the weight loss continues.

Recent evidence check