Unintentional weight loss

Introduction

Unintentional weight loss is defined as a loss of more than 5% of body weight over 6–12 months without deliberate efforts such as dieting or exercise. Unlike intentional weight loss, it is often a clinical red flag that requires investigation. It may indicate underlying malignancy, chronic infection, endocrine disease, gastrointestinal disorders, psychiatric illness, or systemic disease. In older adults, it is associated with increased morbidity, frailty, and mortality.

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Causes of Unintentional Weight Loss

1. Malignancy

• Cancers of the GI tract: Stomach, pancreas, esophagus, colon.

• Hematological malignancies: Lymphoma, leukemia.

• Lung cancer.

• Mechanisms: Tumor-induced hypermetabolism, cachexia, anorexia, cytokine release.

2. Endocrine and Metabolic Disorders

• Hyperthyroidism: Accelerated metabolism with increased appetite.

• Diabetes mellitus (especially uncontrolled type 1): Glucose loss in urine and fat/muscle breakdown.

• Adrenal insufficiency (Addison’s disease): Weight loss, fatigue, low blood pressure, hyperpigmentation.

3. Gastrointestinal Disorders

• Malabsorption syndromes: Celiac disease, Crohn’s disease, chronic pancreatitis.

• Peptic ulcer disease, gastric outlet obstruction: Reduced intake/absorption.

• Chronic diarrhea: Loss of nutrients and fluids.

4. Infections

• Chronic infections: Tuberculosis, HIV/AIDS, chronic hepatitis.

• Parasitic infestations: Worms causing malabsorption or anorexia.

• Recurrent infections: May increase metabolic demand.

5. Psychiatric and Neurological Causes

• Depression and anxiety: Loss of appetite, poor nutrition.

• Eating disorders: Anorexia nervosa, bulimia.

• Dementia or cognitive decline: Forgetting to eat, loss of food interest.

6. Cardiopulmonary Disorders

• Chronic heart failure: Increased metabolic demand, anorexia.

• Chronic obstructive pulmonary disease (COPD): High energy expenditure due to labored breathing.

7. Other Causes

• Chronic kidney disease or liver disease.

• Substance abuse: Alcohol, cocaine, amphetamines.

• Medications: Chemotherapy, SSRIs, digoxin, metformin, topiramate.

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Clinical Presentation

• Main feature: Unexplained weight loss.

• Associated symptoms by system:

  • GI: Abdominal pain, diarrhea, dysphagia, vomiting, hematemesis, melena.

  • Endocrine: Tremors, palpitations, sweating, polyuria, polydipsia.

  • Infections: Fever, night sweats, cough.

  • Psychiatric: Low mood, anhedonia, poor sleep.

• Physical signs: Cachexia, muscle wasting, dehydration, lymphadenopathy, hepatosplenomegaly, thyroid enlargement.

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Diagnosis

1. History and Examination

• Weight loss timeline, appetite changes, dietary intake.

• Red-flag symptoms: GI bleeding, persistent fever, night sweats, dysphagia.

• Psychosocial evaluation.

2. Baseline Investigations

• CBC: Anemia, hematological malignancies.

• ESR/CRP: Inflammation, infection, malignancy.

• Renal and liver function tests.

• Blood glucose/HbA1c: Diabetes.

• Thyroid function tests (TSH, free T4).

• Chest X-ray: TB, lung cancer.

3. Targeted Investigations

• Endoscopy/colonoscopy: GI cancers, ulcers, IBD.

• CT/MRI scans: Tumor or systemic disease detection.

• Stool tests: Malabsorption, occult blood, parasites.

• Serological tests: HIV, hepatitis.

• Endocrine workup: Cortisol, ACTH if Addison’s suspected.

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Management

General Supportive Measures

• Nutritional support: High-protein, high-calorie diet.

• Oral nutritional supplements.

• Enteral (tube feeding) or parenteral nutrition if oral intake inadequate.

• Psychological support and counseling.

1. Malignancy

• Oncological management: Surgery, chemotherapy, radiotherapy.

• Appetite stimulants:

  • Megestrol acetate 160–320 mg orally daily.

  • Dexamethasone 2–4 mg daily (short-term).

2. Endocrine Disorders

• Hyperthyroidism:

  • Carbimazole 20–40 mg daily (titrated).

  • Propylthiouracil 100–150 mg three times daily.

• Diabetes:

  • Insulin therapy for type 1, tailored regimen for type 2.

• Addison’s disease:

  • Hydrocortisone 15–25 mg/day orally (in divided doses).

  • Fludrocortisone 0.05–0.2 mg/day orally if mineralocorticoid needed.

3. Gastrointestinal Disorders

• Celiac disease: Gluten-free diet.

• Chronic pancreatitis: Pancreatic enzyme replacement (Creon® 25,000–50,000 units lipase with meals).

• IBD (Crohn’s/Ulcerative colitis):

  • Mesalazine 2–4 g/day orally.

  • Corticosteroids in acute flares.

4. Infections

• Tuberculosis: 6-month regimen (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol).

• HIV: Antiretroviral therapy (e.g., Tenofovir + Lamivudine + Dolutegravir).

• Parasitic infestations: Albendazole 400 mg single dose (repeated if needed).

5. Psychiatric Causes

• Depression: SSRIs (e.g., Fluoxetine 20 mg daily) + psychotherapy.

• Anorexia nervosa: Nutritional rehabilitation, psychotherapy, sometimes Olanzapine 2.5–10 mg daily for appetite.

6. Cardiopulmonary Disorders

• Heart failure: Diuretics (Furosemide), ACE inhibitors, beta-blockers.

• COPD: Inhaled bronchodilators, steroids, pulmonary rehabilitation, nutritional support.

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Precautions

• Weight loss in elderly patients is more likely due to malignancy or systemic illness—requires thorough evaluation.

• Avoid appetite stimulants until serious causes (cancer, infections) are excluded.

• Long-term steroids can cause immunosuppression, osteoporosis, and hyperglycemia.

• Nutritional supplements should be tailored to patient’s tolerance (avoid aspiration risk).

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Drug Interactions

• Carbimazole + Warfarin: May enhance anticoagulant effect.

• Rifampicin + Oral contraceptives: Reduces efficacy of contraceptives.

• SSRIs + NSAIDs/anticoagulants: Increased bleeding risk.

• Megestrol acetate + Antidiabetics: May worsen hyperglycemia.

• Steroids + Immunosuppressants: Increased infection risk.

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Red-Flag Features

• Rapid weight loss (>10% body weight in 6 months).

• Persistent GI symptoms (dysphagia, hematemesis, melena).

• Fever, night sweats, cough (TB, lymphoma).

• Unexplained anemia or bleeding.

• Confusion, memory decline (dementia-related weight loss).