Unintentional weight loss

Unintentional weight loss is involuntary loss of body weight, clinically important when it exceeds 5% of usual weight over 6 to 12 months, or 5% in 1 month or 10% in 6 months. It indicates malignancy, chronic infection, endocrine disease, gastrointestinal disease, mental illness, drug effect or social deprivation until proved otherwise. Even when no cause is found, it predicts higher mortality.

Epidemiology. It affects up to one in 10 older adults in a year. In series of patients investigated, cancer accounts for roughly 15% to 30%, non malignant gastrointestinal disease 10% to 20%, psychiatric disease 10% to 20%, endocrine disease about 5% to 10%, drugs and social causes the rest, and about a fifth remain unexplained. In sub-Saharan Africa HIV, tuberculosis, helminths and food insecurity weigh heavily.

Mechanisms.

• Reduced intake: anorexia, dysphagia, early satiety, nausea, dental disease, depression, dementia, social deprivation, food insecurity.
• Malabsorption or loss: coeliac disease, pancreatic insufficiency, bile salt loss, protein losing enteropathy, glycosuria, vomiting, diarrhoea.
• Increased energy needs: hyperthyroidism, fever, chronic infection, cancer, heart or lung failure, phaeochromocytoma.
• Cytokine driven catabolism and muscle loss: cachexia (interleukin 1, interleukin 6, tumour necrosis factor).

Classification.

• With appetite preserved or increased: hyperthyroidism, diabetes mellitus, malabsorption, phaeochromocytoma, uncontrolled HIV, helminth infestation.
• With anorexia: cancer, chronic infection, depression, heart failure, kidney failure, liver disease, drugs.
• Cachexia: weight loss over 5% in 12 months with anorexia, fatigue, reduced muscle strength, low fat free mass and raised inflammatory markers (C reactive protein over 5 mg/L, haemoglobin under 120 g/L, albumin under 32 g/L).
• Sarcopenia: loss of muscle mass and function, often without weight change.

History.

• Verify the loss with records, clothing fit and collateral history. Amount, time frame, usual weight and weight pattern.
• Appetite, food intake, dietary restriction, food access, swallowing, nausea, vomiting, early satiety, dysphagia, abdominal pain, bowel habit, steatorrhoea, rectal bleeding, melaena.
• Respiratory: cough, haemoptysis, breathlessness. Fever, night sweats, itch, lumps.
• Endocrine: polyuria, polydipsia, heat intolerance, palpitations, tremor, salt craving, postural dizziness.
• Mood, sleep, cognition, bereavement, anxiety, eating behaviour, body image, delusions about food.
• Alcohol, tobacco, cannabis, stimulants, injecting drug use.
• Drugs: metformin, GLP-1 receptor agonists, SGLT2 inhibitors, levothyroxine excess, digoxin, SSRIs, levodopa, antiepileptics (topiramate, zonisamide), stimulants, chemotherapy, antiretrovirals, antibiotics, bisphosphonates, laxatives and diuretics.
• Social: poverty, isolation, caring role, dentures, difficulty shopping or cooking, abuse or neglect.
• HIV and tuberculosis risk, travel, animal exposure, family history of cancer, inflammatory bowel disease or coeliac disease.

Examination.

• Weight, height, body mass index, mid upper arm circumference, grip strength, hydration, vital signs.
• Wasting (temporal, interossei), oedema, pallor, jaundice, clubbing, cachexia.
• Lymph nodes, oral candidiasis, dentition and mucosal lesions, thyroid.
• Chest and heart. Abdomen: masses, organomegaly, ascites, tenderness. Rectal examination and stool colour. Breast, testicular, pelvic and skin examination.
• Neurological examination (Parkinsonism, bulbar signs, tremor), mental state, Mini-Cog or equivalent, depression screen (Geriatric Depression Scale or PHQ-9).
• Screening tool: Malnutrition Universal Screening Tool.
• Scoring: weight loss over 5% scores 1, over 10% scores 2; body mass index under 18.5 scores 2, 18.5 to 20 scores 1; acute disease with no intake for over 5 days scores 2; a total of 2 or more is high risk.

Red flags.

• Loss over 10% in 6 months, rapid loss, cachexia.
• Dysphagia, odynophagia, persistent vomiting, haematemesis, melaena, rectal bleeding, change in bowel habit, jaundice, abdominal mass.
• Haemoptysis, persistent cough, lymphadenopathy, night sweats, fever.
• Anaemia, iron deficiency, new diabetes, hypercalcaemia.
• Age over 50 with new symptoms, smoking, HIV, tuberculosis contact.
• Severe depression, psychosis or suicidal thoughts. Suspected restrictive eating disorder with instability.

Malignancy. Oesophageal, gastric, pancreatic, colorectal, hepatobiliary, lung, head and neck, ovarian, renal, prostate, breast cancers; lymphoma, leukaemia, myeloma; metastatic disease of unknown primary.

Gastrointestinal (non malignant). Peptic ulcer disease, Helicobacter pylori gastritis, gastro-oesophageal reflux disease, achalasia, oesophageal stricture, gastroparesis, coeliac disease, inflammatory bowel disease, chronic pancreatitis and exocrine pancreatic insufficiency. Small intestinal bacterial overgrowth, tropical sprue, Whipple disease, chronic mesenteric ischaemia, chronic liver disease and cirrhosis, gallstone disease, dental disease and poor dentition. Intestinal parasites (giardiasis, strongyloidiasis, hookworm, schistosomiasis, amoebiasis).

Endocrine and metabolic. Hyperthyroidism, diabetes mellitus (including type 1 and latent autoimmune diabetes), adrenal insufficiency, hypercalcaemia (hyperparathyroidism), phaeochromocytoma, hypopituitarism, uraemia and chronic kidney disease.

Infective. HIV infection, tuberculosis, infective endocarditis, hepatitis B and C, visceral leishmaniasis, brucellosis, schistosomiasis, histoplasmosis and other mycoses, chronic abscess or osteomyelitis, strongyloidiasis.

Cardiorespiratory. Heart failure (cardiac cachexia), chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, pulmonary hypertension.

Rheumatological and inflammatory. Rheumatoid arthritis, systemic lupus erythematosus, vasculitis, giant cell arteritis, polymyalgia rheumatica, sarcoidosis, systemic sclerosis (oesophageal and bowel involvement).

Neurological. Dementia, Parkinson disease, stroke with dysphagia, motor neurone disease, bulbar disease, multiple sclerosis, myasthenia gravis.

Psychiatric and behavioural. Depression, anxiety, anorexia nervosa and other eating disorders (restriction, purging), avoidant restrictive food intake disorder, psychosis (delusions about poisoning), bereavement, substance and alcohol use disorder.

Drugs. As listed in the history.

Social and functional. Poverty and food insecurity, social isolation, inability to shop or cook, dentures and oral pain, disability, elder abuse or neglect, institutional care.

1. Confirm weight loss objectively with records and serial weights. Exclude intentional loss, fluid shifts and mis measurement.
2. Full history, drug review and examination, including mental state, oral cavity and cognition. Many causes are evident from this step.
3. First line tests:
   • Full blood count with film, ESR and C reactive protein, urea, creatinine and electrolytes, calcium, liver function tests with albumin.
   • Glucose or HbA1c, thyroid stimulating hormone, ferritin, vitamin B12 and folate, lactate dehydrogenase.
   • Urinalysis, HIV test with consent, tissue transglutaminase IgA with total IgA, and chest radiograph.
4. Gastrointestinal: faecal immunochemical test and faecal calprotectin for lower gastrointestinal symptoms; stool microscopy and antigen tests for Giardia, and stool for parasites in endemic regions; faecal elastase (under 200 microgram/g suggests exocrine pancreatic insufficiency); Helicobacter pylori testing.
5. Imaging: abdominal ultrasound; CT of chest, abdomen and pelvis if the first line panel is non diagnostic or red flags exist.
6. Endoscopy: upper endoscopy for dysphagia, vomiting, epigastric symptoms or iron deficiency; colonoscopy for bowel symptoms, anaemia or positive faecal tests.
7. Targeted tests by clue: tuberculosis tests, serum protein electrophoresis, 08:00 cortisol, morning plasma metanephrines, age appropriate PSA and mammography screening, bone marrow, echocardiography.
8. When the first panel is normal and no clue exists, observe with serial weights over 3 to 6 months rather than extending tests. Most patients with a normal workup have a good prognosis, but a repeat targeted review is needed if weight loss continues.

Limits. Normal baseline tests lower the likelihood of serious organic disease but do not exclude cancer. Albumin is a marker of inflammation more than nutrition. Faecal tests miss upper gastrointestinal cancer. Imaging has low yield when history, examination and baseline tests are all normal.

Treat the cause. Direct treatment toward malignancy, infection, thyroid disease, diabetes, gastrointestinal disease, depression, heart or lung disease, and withdrawn drugs. Stop or reduce drugs that reduce appetite or cause nausea.

Nutritional support (all patients with significant loss).

• Dietitian review. Estimated needs: energy 25 to 30 kcal/kg daily, protein 1.2 to 1.5 g/kg daily (higher in illness and older adults), adjusted to kidney and liver function.
• Food first: small frequent energy dense meals, fortified foods, snacks, avoiding diet restriction, and social eating. Treat dental and swallowing problems.
• Oral nutritional supplements providing 300 to 600 kcal and 12 to 24 g protein daily when food alone is inadequate.
• Micronutrients: multivitamin, thiamine, zinc, vitamin D, calcium as indicated.
• Enteral tube feeding (nasogastric, gastrostomy) when oral intake remains inadequate for 5 to 10 days, or earlier if severely malnourished; parenteral nutrition when the gut cannot be used.

Refeeding syndrome. High risk when body mass index is under 16, weight loss is over 15% in 3 to 6 months, intake has been minimal for over 10 days, or potassium, phosphate or magnesium are low.

Check and correct electrolytes before feeding. Start at 10 kcal/kg daily (5 kcal/kg in extreme cases) increasing over 4 to 7 days. Give thiamine 200 to 300 mg orally daily (or 100 mg intravenously two to three times daily) before and during the first 10 days of feeding. Monitor potassium, phosphate, magnesium and glucose daily in the first week.

Appetite stimulation (limited, selective use).

• Mirtazapine 15 mg orally at night, increased to 30 mg, especially with depression or insomnia.
• Megestrol acetate 160 mg orally daily, increased to 400 to 800 mg daily, in cancer or HIV cachexia for weight gain (no survival benefit; risk of venous thromboembolism, adrenal suppression and oedema; avoid with thrombosis history).
• Dexamethasone 2 to 4 mg orally each morning for short courses of 1 to 3 weeks in palliative care.
• Metoclopramide 10 mg orally 30 minutes before meals three times daily for early satiety (halve the dose when eGFR is under 60 mL/min; limit duration because of tardive dyskinesia risk).
• Cannabinoids are not advised for appetite.

Specific problems. Treat constipation, pain and nausea. Address social causes: food banks, meal services, home help, carer support, safeguarding. Review care home arrangements.

Monitoring. Weigh weekly at first (every 1 to 2 weeks), then monthly. Reassess red flags and repeat key tests if weight loss continues. Review at 4 to 6 weeks and again at 3 months.

Referral and escalation. Urgent investigation or 2 week cancer referral for red flags. Dietetic service for all with high risk screening scores. Gastroenterology, endocrinology, haematology, geriatrics, psychiatry or palliative care as indicated.

Admission. Body mass index under 15, severe dehydration, electrolyte disturbance, refeeding risk, haemodynamic instability. Also severe suspected eating disorder (heart rate under 40 beats/minute, systolic pressure under 90 mmHg, potassium under 3.0 mmol/L, prolonged QTc), inability to eat or drink, or need for urgent diagnostic work up.

Safety netting. Return for vomiting, black stool, rectal bleeding, jaundice, persistent fever or sweats, breathlessness, new lumps, confusion, or continuing loss despite supplements.

Special groups.

• Older adults: sarcopenia and frailty, depression, dental problems, polypharmacy and social isolation; avoid weight loss diets, review drug causes first.
• Pregnancy: hyperemesis gravidarum, thyroid disease and infection.
• Children: growth faltering needs paediatric growth assessment, feeding history and screening for infection, coeliac disease and chronic illness.
• HIV and tuberculosis endemic regions: screen for both, provide ready to use therapeutic or supplementary foods where indicated, and treat helminths with albendazole 400 mg orally once.