Causes of Unintentional Weight Loss
Unintentional weight loss is most commonly caused by cancer, gastrointestinal disorders, psychological conditions, and metabolic disorders, with malignancy accounting for approximately 24% of cases and non-malignant causes representing about 60% of cases. 1, 2
Definition and Significance
- Significant weight loss is defined as >5% of body weight over 6-12 months
- Severe weight loss is >10% of body weight over the same period
- Unintentional weight loss is associated with increased morbidity and mortality, particularly in older adults
Major Causes
1. Malignancy (24% of cases)
- Gastrointestinal cancers (53% of malignant causes) 2
- Other solid tumors
- Hematologic malignancies
- Mechanisms include:
- Reduced food intake due to tumor effects
- Systemic inflammation
- Metabolic derangements
- Cancer cachexia (characterized by inflammation, negative protein/energy balance, muscle loss) 1
2. Non-malignant Gastrointestinal Disorders (30% of cases) 2
- Malabsorption syndromes
- Inflammatory bowel disease
- Peptic ulcer disease
- Celiac disease
- Chronic pancreatitis
- Oral/dental problems (particularly in elderly)
- Poor dentition
- Xerostomia (dry mouth)
- Oral ulcerations
3. Psychological Disorders (11-16% of cases) 1, 2
- Depression
- Anxiety
- Dementia
- Eating disorders
- Social isolation
4. Metabolic and Endocrine Disorders
- Diabetes mellitus
- Weight loss through glycosuria and caloric loss
- Insulin deficiency affecting glucose metabolism 1
- Hyperthyroidism
- Adrenal insufficiency
5. Medication-Related Causes
- Side effects of medications
- Polypharmacy interfering with taste or causing nausea 3
- Common culprits:
- Chemotherapeutic agents
- Antibiotics
- Digoxin
- SSRIs
- Metformin
6. Chronic Infections
- Tuberculosis
- HIV/AIDS
- Parasitic infections
- Subacute bacterial endocarditis
7. Social Factors
- Food insecurity leading to inadequate caloric intake 1
- Poverty
- Inability to shop or prepare meals
- Social isolation
8. Other Causes
- Chronic organ failure (heart, lung, kidney, liver)
- Neurological disorders affecting swallowing
- Substance abuse
- Chronic pain
9. Idiopathic/Unknown Causes
- No identifiable cause in 16-28% of cases 3, 2
- Prognosis for unknown causes similar to non-malignant causes 2
Age-Related Considerations
Elderly Patients (≥65 years)
- Oral disorders are the second most common cause after non-hematologic malignancies 4
- Higher risk of malnutrition due to:
- Decreased appetite
- Altered taste sensation
- Swallowing difficulties
- Cognitive impairment
- Social isolation
Clinical Implications
- A readily identifiable cause is not found in up to 28% of cases initially 3
- When baseline evaluation is unremarkable, a three- to six-month observation period is justified
- Long-term follow-up is essential as malignancies may be undetectable until death 4
- Regular monitoring (e.g., yearly visits) should continue longer than typically reported periods
- Autopsies should be pursued in cases of unsolved deaths with persistent unexplained weight loss 4
Understanding these diverse causes is essential for developing an appropriate diagnostic approach and management plan for patients presenting with unintentional weight loss.