What are the possible causes of unintentional weight loss?

Causes of Unintentional Weight Loss

Unintentional weight loss (defined as >5% over 3-6 months or >10% regardless of timeframe) requires systematic evaluation for malignancy, endocrine disorders, gastrointestinal disease, psychiatric conditions, and chronic infections, with cancer being the most critical diagnosis to exclude given its prevalence in 30-80% of cases depending on tumor type. 1, 2

Medical Causes by Category

Malignancy (Most Critical to Exclude)

• Cancer is the leading cause, with weight loss occurring in 30-80% of patients depending on primary tumor type 2
• Severe involuntary weight loss (>10% over 6 months) occurs in 15% of all cancer patients at diagnosis 2
• Pancreatic and gastric cancers show the highest association, with 85% of patients experiencing weight loss at diagnosis 2
• Cancer cachexia involves metabolic disturbances from tumor-produced catabolic factors that prevent adaptation to nutrient deprivation, unlike simple starvation 2
• Weight loss in cancer patients predicts reduced quality of life, increased treatment toxicity, decreased tumor response, and reduced survival, with 4-23% of terminal cancer patients dying directly from cachexia 2

Endocrine Disorders

• Hyperthyroidism causes weight loss in 90% of patients through increased metabolic rate, though 10% paradoxically gain weight 3
• Levothyroxine overdosage produces hyperthyroid symptoms including increased appetite with weight loss, heat intolerance, and excessive sweating 4
• Diabetes mellitus commonly presents with unintentional weight loss, particularly in young adults with new-onset type 2 diabetes 1
• The American Diabetes Association recommends screening with fasting glucose or HbA1c in all patients with unexplained weight loss 1

Infectious Disease

• HIV infection causes weight loss at all stages of disease progression 2
• HIV Wasting Syndrome is defined as weight loss ≥10% with fever and/or diarrhea of unknown origin 2
• Approximately one-third of HIV patients experience weight loss during the asymptomatic latent phase 2

Psychiatric and Behavioral Disorders

• Eating disorders including anorexia nervosa and bulimia cause significant weight loss, particularly in younger women 1, 2
• Intentional insulin or medication omission to induce weight loss requires mental health evaluation 2
• Diabetes distress affects 18-45% of patients and can impact eating behaviors and self-care 2
• Cognitive impairment affecting ability to maintain adequate nutrition 2

Medication-Induced Weight Loss

• Many medications cause weight loss through decreased appetite, altered taste perception, or nausea/vomiting 2
• Common culprits include stimulants, GLP-1 receptor agonists, and topiramate 2
• Conversely, antipsychotics, tricyclic antidepressants, glucocorticoids, and beta-blockers typically cause weight gain 2

Gastrointestinal Disorders

• Malabsorption syndromes, inflammatory bowel disease, and chronic pancreatitis impair nutrient absorption 5
• Physical limitations to food intake include mouth ulcers and GI obstruction 5

Malnutrition and Cachexia

• Disease-related malnutrition results from systemic inflammation causing anorexia and tissue breakdown 5
• Cachexia is characterized by involuntary weight loss with ongoing skeletal muscle loss that cannot be reversed by conventional nutrition care 5
• Sarcopenia (low lean body mass) often accompanies weight loss, with fatigue, decreased strength, and limited physical function 5
• Sarcopenic obesity (low lean body mass in obese individuals) is frequently overlooked but predicts adverse outcomes 5

Diagnostic Approach

Initial Assessment

• Quantify weight loss by documenting current weight, calculating BMI (normal 18.5-25.0 kg/m²), and determining percentage loss over time 1
• Establish onset, duration, and pattern of weight loss 1
• Document associated symptoms: fever, night sweats, changes in bowel habits 1

First-Tier Laboratory Testing

• Complete blood count, basic metabolic panel, liver function tests 2
• Thyroid function tests (TSH, free T4) 2
• Diabetes screening (fasting glucose or HbA1c) 1
• Inflammatory markers (CRP, ESR) to identify inflammatory, infectious, or malignant processes 1, 2
• Lactate dehydrogenase, ferritin, protein electrophoresis 2
• Urinalysis, fecal occult blood testing 2
• Chest radiography 2

Age-Specific Considerations

• In younger adults, prioritize diabetes screening as type 2 diabetes frequently presents with unintentional weight loss and dehydration 1
• In younger women, maintain high suspicion for eating disorders 1

When Initial Workup is Negative

• When no cause is identified (occurs in 6-28% of cases), a three- to six-month observation period is recommended 2

Management Priorities

Nutritional Support

• Refer to a registered dietitian (preferably certified specialist in oncology) if weight loss continues or BMI <18.5 kg/m² 5, 1
• Caution regarding refeeding syndrome in patients with weight loss >15% in 3-6 months 1
• For patients at risk of unintentional weight loss, consume smaller, more frequent meals with minimal liquids during meals 5
• Fortified, commercially prepared or homemade nutrient-dense beverages can improve energy and nutrient intake when food alone is insufficient 5

Cancer-Related Weight Loss

• During active cancer treatment, goals include preventing nutrient deficiencies, achieving/maintaining healthy weight, preserving lean body mass, and minimizing nutrition-related side effects 5
• Dietary counseling during cancer treatment improves outcomes including fewer treatment-related symptoms, improved quality of life, and improved dietary intake 5
• Megestrol acetate can enhance appetite in cancer patients struggling to maintain weight 5
• Enteral and parenteral nutrition should be used selectively with clear purpose, recognizing overall treatment goals 5

HIV-Related Weight Loss

• Protein intake should achieve 1.2 g/kg body weight/day in stable phases and may increase to 1.5 g/kg during acute illness 2

Catabolic Illness

• Recent weight loss >10% necessitates thorough nutrition assessment 5
• Unintentional weight loss of 10-20% suggests moderate protein-calorie malnutrition; >20% indicates severe malnutrition 5
• Hospitalized patients require 25-35 kcal/kg body weight, with protein needs of 1.0 g/kg for mildly stressed patients and 1.5 g/kg for moderately to severely stressed patients 5

Critical Pitfalls to Avoid

• Do not overlook sarcopenic obesity: muscle loss is frequently missed in obese individuals due to excess fat and extracellular water, yet it predicts adverse outcomes 5
• Do not assume weight loss is intentional in overweight/obese patients—they can have serious underlying disease 5
• Do not delay diabetes screening in younger adults with weight loss, as this is a common presentation 1
• Do not overfeed catabolic patients, as this exacerbates hyperglycemia, causes abnormal liver function, and increases oxygen consumption 5