What are the causes of sudden weight loss?

Causes of Sudden Weight Loss

Sudden weight loss is most commonly caused by malignancy (up to 36%), gastrointestinal disorders, psychiatric conditions, and endocrine disorders, with approximately 23% of cases remaining unexplained despite thorough investigation. 1

Medical Causes

Malignancy

• Cancer accounts for up to one-third of cases of unintentional weight loss, particularly affecting the gastrointestinal tract 2, 1
• Patients with cancer-related weight loss often present with abnormal physical findings, lower serum albumin levels, and higher alkaline phosphatase values 1
• Weight loss is frequently the first symptom occurring in cancer patients, reported in 30-80% of cases depending on the primary tumor type 3
• Severe involuntary weight loss (>10% of usual body weight over 6 months) occurs in 15% of all patients at the time of cancer diagnosis 3
• Pancreatic and stomach cancers are associated with weight loss in 85% of patients at diagnosis 3

Gastrointestinal Disorders

• Nonmalignant gastrointestinal disorders are common causes of unintentional weight loss 2, 1
• Malabsorption syndromes can lead to significant weight loss despite adequate caloric intake 4
• Conditions such as inflammatory bowel disease, celiac disease, and chronic pancreatitis can impair nutrient absorption 4

Endocrine Disorders

• Hyperthyroidism causes weight loss in approximately 90% of affected individuals despite increased appetite 5
• Diabetes mellitus, particularly uncontrolled, can lead to weight loss through glucosuria and metabolic derangements 1
• Adrenal insufficiency may present with weight loss alongside other symptoms 1

Infectious Diseases

• HIV infection can cause weight loss at all stages of disease progression 6
• HIV Wasting Syndrome is defined as weight loss of ≥10% with fever and/or diarrhea of unknown origin 6
• Approximately one-third of patients experience weight loss during the asymptomatic latent phase of HIV infection 6
• Chronic infections such as tuberculosis can cause progressive weight loss 2

Psychiatric and Psychological Causes

Mental Health Disorders

• Depression and anxiety are significant contributors to unintentional weight loss, particularly in older adults 2, 7
• Psychiatric disorders are among the most common causes of weight loss in institutionalized older adults 7
• Diabetes distress affects 18-45% of patients and can impact eating behaviors and self-care 3

Disordered Eating

• Anorexia nervosa, bulimia, and other eating disorders can cause significant weight loss 3
• Intentional omission of insulin or medications to cause weight loss (particularly in diabetes patients) requires mental health evaluation 3

Medication-Related Causes

Medication Side Effects

• Many medications can cause weight loss through various mechanisms 4:
  • Decreased appetite (stimulants, some antidepressants)
  • Altered taste perception (antibiotics, antihistamines)
  • Nausea/vomiting (chemotherapy, antibiotics)
  • Increased metabolism (thyroid medications)
• Polypharmacy in older adults increases the risk of medication-related weight loss 2

Medication Review

• Common medications associated with weight changes include 3:
  • Weight gain: antipsychotics (clozapine, olanzapine), tricyclic antidepressants, glucocorticoids, beta-blockers
  • Weight loss: some stimulants, GLP-1 receptor agonists, topiramate

Social and Functional Causes

Social Factors

• Isolation and financial constraints may contribute to unintentional weight loss, particularly in older adults 2
• Limited access to food, inability to prepare meals, and poverty can lead to inadequate nutrition 2

Functional Limitations

• Difficulties with chewing or swallowing can significantly impact nutritional intake 2
• Mobility issues limiting access to food preparation or shopping 2
• Cognitive impairment affecting ability to maintain adequate nutrition 3

Cancer-Related Cachexia

Mechanisms

• Cancer cachexia is characterized by depletion of both fat and muscle mass with preservation of central protein mass 3
• Cachexia involves metabolic disturbances caused by tumor-produced catabolism factors 3
• Cachexia differs from simple starvation as cachectic patients fail to adapt their energy requirements to nutrient deprivation 3
• Inflammatory response in cachexia prevents substantial benefit from nutritional support 3

Impact

• Weight loss in cancer patients is associated with reduced quality of life, lower activity levels, increased treatment-related adverse reactions, reduced tumor response to treatment, and reduced survival 3
• 4-23% of terminal cancer patients ultimately die because of cachexia 3

Diagnostic Approach

Initial Evaluation

• Unintentional weight loss is defined as loss of at least 5% of body weight over 6 months 4
• Recommended initial tests include 2:
  • Complete blood count
  • Basic metabolic panel
  • Liver function tests
  • Thyroid function tests
  • Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate)
  • Lactate dehydrogenase, ferritin, protein electrophoresis
  • Urinalysis
  • Age-appropriate cancer screenings
  • Chest radiography and fecal occult blood testing

When Initial Evaluation is Unremarkable

• When no cause is identified (occurs in 6-28% of cases), a three- to six-month observation period is recommended 2
• Close follow-up is warranted as malignancy may declare itself over time 7

Management Considerations

Treatment Principles

• Treatment should focus on the underlying cause when identified 2, 7
• Dietary modifications should consider patient preferences and any chewing or swallowing difficulties 2
• Nutritional counseling with or without oral supplements can be effective for preserving nutritional status 6
• For 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 6

Important Caveats

• Appetite stimulants and high-calorie supplements alone are generally not recommended without addressing underlying causes 2
• Treatment should focus on feeding assistance, addressing contributing medications, providing appealing foods, and social support 2
• Patients with significant weight loss should be screened for malnutrition, especially those who have undergone metabolic surgery or are on weight management pharmacotherapy 3