Common Causes of Weight Loss
Unintentional weight loss can be caused by cancer, metabolic disorders, psychological factors, medication side effects, or inadequate nutritional intake, and requires thorough investigation to identify the underlying cause. 1
Medical Causes of Weight Loss
Cancer-Related Causes
Malignancy: Cancer can cause weight loss through multiple mechanisms 1:
- Reduced food intake due to primary anorexia
- Metabolic derangements (elevated resting metabolic rate, insulin resistance, lipolysis)
- Systemic inflammation and catabolic factors
- Tumor-derived substances affecting appetite and metabolism
Cancer-specific symptoms leading to reduced intake 1:
- Oral ulceration, xerostomia, poor dentition
- Intestinal obstruction, malabsorption
- Nausea, vomiting, reduced intestinal motility
- Chemosensory alterations
- Pain
Endocrine and Metabolic Disorders
- Hyperthyroidism: Causes weight loss in approximately 90% of patients 2
- Diabetes mellitus: Uncontrolled diabetes can lead to weight loss through:
- Glycosuria and caloric loss
- Insulin deficiency affecting glucose metabolism 1
- Adrenal insufficiency
Gastrointestinal Disorders
- Malabsorption syndromes:
- Celiac disease
- Inflammatory bowel disease
- Pancreatic insufficiency
- Gastrointestinal infections
- Dysphagia or odynophagia limiting food intake
Psychological Factors
- Depression and anxiety disorders
- Eating disorders:
- Anorexia nervosa
- Bulimia nervosa
- Dementia with associated behavioral changes affecting eating
Medication-Related Weight Loss
- Medications that commonly cause weight loss:
- Chemotherapeutic agents
- Some antidepressants
- Stimulants
- Some diabetes medications
- Thyroid replacement therapy (excessive doses)
Lifestyle and Social Factors
Inadequate caloric intake due to:
- Food insecurity 1
- Limited access to healthy food options
- Cultural circumstances
- Social isolation
- Financial constraints
Increased physical activity without compensatory increase in caloric intake 3
Cachexia and Wasting Syndromes
Cancer cachexia: Characterized by 1:
- Systemic inflammation
- Negative protein and energy balance
- Loss of skeletal muscle with or without fat loss
- Decreased functional capacity
Other wasting syndromes:
- HIV/AIDS-associated wasting
- Cardiac cachexia
- Renal cachexia
- COPD-related weight loss
Intentional Weight Loss
Lifestyle interventions 3:
- Caloric restriction (500-750 kcal/day deficit)
- Increased physical activity (150-300 minutes/week)
- Behavioral strategies
Pharmacotherapy for obesity 1:
- FDA-approved medications for BMI ≥30 or BMI ≥27 with comorbidities
Bariatric surgery for severe obesity 1
Diagnostic Approach to Unintentional Weight Loss
Quantify the weight loss:
- Significant weight loss is defined as >5% of body weight over 6-12 months 1
- Severe weight loss is >10% of body weight
Evaluate for red flags:
- Rapid weight loss
- Associated symptoms (fever, night sweats, pain)
- Age >65 years
- History of tobacco use or alcohol abuse
Laboratory and diagnostic testing based on clinical suspicion:
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Inflammatory markers
- Age-appropriate cancer screening
- Additional testing based on symptoms
Management Considerations
- Treatment should target the underlying cause when identified
- Nutritional support may be necessary:
- Oral nutritional supplements
- Enteral or parenteral nutrition in severe cases 1
- Pharmacologic appetite stimulants in select cases
- Oxandrolone may be indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma 4
Monitoring and Follow-up
- Regular monitoring of weight and nutritional status
- Reassessment if weight loss continues despite intervention
- Consideration of specialist referral for refractory cases
Weight loss can significantly impact quality of life, with studies showing that even moderate weight loss in cancer patients is associated with psychological distress and lower quality of life 5. Therefore, prompt identification and management of the underlying cause is essential.