Involuntary weight loss generally develops over weeks or months. It can be a sign of a significant physical or mental disorder and is associated with an increased risk for mortality. The causative disorder may be obvious (eg, chronic diarrhea due to a malabsorption syndrome Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more ) or occult (eg, an undiagnosed cancer). This discussion focuses on patients who present for weight loss rather than those who lose weight as a more-or-less expected consequence of a known chronic disorder (eg, metastatic cancer, end-stage chronic obstructive pulmonary disease [COPD]).
Weight loss is typically considered clinically important if it exceeds 5% of body weight or 5 kg over 6 months. However, this traditional definition does not distinguish between loss of lean and fat body mass, which can lead to different outcomes. Also, accumulation of edema (eg, in heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more 
or chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more 
) can mask clinically important loss of lean body mass.
In addition to weight loss, patients may have other symptoms, such as anorexia, fever, or night sweats, due to the underlying disorder. Depending on the cause and its severity, symptoms and signs of nutritional deficiency (see Overview of Vitamins Overview of Vitamins Vitamins may be Fat soluble (vitamins A, D, E, and K) Water soluble (B vitamins and vitamin C) The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B2), thiamin (B1)... read more ) may also be present.
The overall incidence of significant involuntary weight loss is about 5% per year in the US. However, incidence increases with aging, often reaching 50% among nursing home patients.
Pathophysiology of Involuntary Weight Loss
Weight loss results when more calories are expended than taken in (ingested and absorbed). Disorders that increase expenditure or decrease absorption tend to increase appetite. More commonly, inadequate caloric intake is the mechanism for weight loss and such patients tend to have decreased appetite. Sometimes, several mechanisms are involved. For example, cancer tends to decrease appetite but also increases basal caloric expenditure by cytokine-mediated mechanisms.
Etiology of Involuntary Weight Loss
Many disorders cause involuntary weight loss, including almost any chronic illness of sufficient severity. However, many of these are clinically obvious and have typically been diagnosed by the time weight loss occurs. Other disorders are more likely to manifest as involuntary weight loss (see table Some Causes of a Presenting Symptom of Involuntary Weight Loss Some Causes of a Presenting Symptom of Involuntary Weight Loss Involuntary weight loss generally develops over weeks or months. It can be a sign of a significant physical or mental disorder and is associated with an increased risk for mortality. The causative... read more ).
With increased appetite, the most common occult causes of involuntary weight loss are
With decreased appetite, the most common occult causes of involuntary weight loss are
In some disorders that cause involuntary weight loss, other symptoms tend to be more prominent, so that weight loss is usually not the chief complaint. Examples include the following:
Some malabsorptive disorders: Gastrointestinal tract surgery and cystic fibrosis
Chronic inflammatory disorders: Severe rheumatoid arthritis
Gastrointestinal disorders: Achalasia, celiac disease, Crohn disease, chronic pancreatitis, esophageal obstructive disorders, ischemic colitis, diabetic enteropathy, peptic ulcer disease, progressive systemic sclerosis, ulcerative colitis (late)
Severe, chronic heart and lung disorders: Chronic obstructive pulmonary disease (COPD), heart failure (stage III or IV), restrictive lung disease
Mental disorders (known and poorly controlled): Anxiety, bipolar disorder, depression, schizophrenia
Neurologic disorders: Amyotrophic lateral sclerosis, dementia, multiple sclerosis, myasthenia gravis, Parkinson disease, stroke
Social problems: Poverty, social isolation
With chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more and heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more , accumulation of edema may mask loss of lean body weight.
Evaluation of Involuntary Weight Loss
Evaluation focuses on detection of otherwise occult causes. Because these are numerous, evaluation must be comprehensive.
History
History of present illness includes questions about the amount and time course of weight loss. A report of weight loss may be inaccurate; thus, corroborating evidence should be sought, such as weight measurement in old medical records, changes in size of clothes, or confirmation by family members. Appetite, food intake, swallowing, and bowel patterns should be described. For repeat evaluations, patients should keep a food diary because recollections of food intake are often inaccurate. Nonspecific symptoms of potential causes are noted, such as fatigue, malaise, fevers, and night sweats.
Review of systems must be complete, seeking symptoms in all major organ systems.
Past medical history may reveal a disorder capable of causing weight loss. Also addressed should be use of prescription drugs, over-the-counter drugs, recreational drugs, and herbal products. Social history may reveal changes in living situations that could explain why food intake is decreased (eg, loss of loved one, loss of independence or job, loss of communal eating routine).
Physical examination
Vital signs are checked for fever, tachycardia, tachypnea, and hypotension. Weight is measured and body mass index (BMI) Diagnosis Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more is calculated. Triceps skinfold thickness and mid upper arm circumference can be measured to estimate lean body mass Diagnosis Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more . BMI and lean body mass estimates are helpful mainly for detecting a trend in follow-up visits.
General examination should be particularly comprehensive, including examination of the heart, lungs, abdomen, head and neck, breasts, neurologic system, rectum (including prostate examination and testing for occult blood), genitals, liver, spleen, lymph nodes, joints, skin, mood, and affect.
Red flags
Fever, night sweats, generalized lymphadenopathy
Bone pain
Dyspnea, cough, hemoptysis
Inappropriate fear of weight gain in an adolescent or young woman
Polydipsia and polyuria
Headache, jaw claudication, and/or visual disturbances in an older adult
Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, retinal artery emboli
Interpretation of findings
Interpretations of some findings are listed in the table Interpretation of Selected Findings in Involuntary Weight Loss Interpretation of Selected Findings in Involuntary Weight Loss Involuntary weight loss generally develops over weeks or months. It can be a sign of a significant physical or mental disorder and is associated with an increased risk for mortality. The causative... read more . Abnormal findings suggest the cause of weight loss in about half or more patients, including patients eventually diagnosed with cancer.
Although many chronic disorders can cause weight loss, the clinician must not be too quick to assume that an existing disorder is the cause. Although the existing disorder is the likely cause in patients whose condition has remained poorly controlled or is deteriorating, stable patients who suddenly begin losing weight without a worsening of that disorder may have developed a new condition (eg, patients with stable ulcerative colitis may begin losing weight because they developed a colon cancer).
Testing
Age-appropriate cancer screening (eg, colonoscopy, mammography) is indicated if not previously done. Other testing is done for disorders suspected based on abnormal findings in the history or examination. There are no widely accepted guidelines on other testing for patients without such focal abnormal findings. One suggested approach is to do the following tests:
Chest x-ray
Urinalysis
Complete blood count (CBC) with differential count
Erythrocyte sedimentation rate (ESR) or C-reactive protein
HIV testing
Serum chemistries (serum electrolytes, calcium, hepatic and renal function tests)
Thyroid-stimulating hormone (TSH) level
Abnormal results on these tests are followed with additional testing as indicated. If all test results are normal and clinical findings are otherwise normal, extensive further testing (eg, CT, MRI) is not recommended. Such testing is very low yield and can be misleading and harmful by revealing incidental, unrelated findings. Such patients should be taught how to ensure adequate caloric intake and have a follow-up evaluation in about 1 month that includes a weight measurement. If patients have continued to lose weight, the entire history and physical examination should be repeated because patients may share important, previously undisclosed, information, and new, subtle physical abnormalities may then be detected. If weight loss continues and all other findings remain normal, further testing (eg, CT, MRI) should be considered.
Treatment of Involuntary Weight Loss
The underlying disorder is treated. If an underlying disorder causes undernutrition and is difficult to treat, nutritional support Overview of Nutritional Support Many undernourished patients need nutritional support, which aims to increase lean body mass. Oral feeding can be difficult for some patients with anorexia or with eating or absorption problems... read more should be considered. Helpful general behavioral measures include encouraging patients to eat, assisting them with feeding, offering snacks between meals and before bedtime, providing favorite or strongly flavored foods, and offering only small portions. If behavioral measures are ineffective and weight loss is extreme, enteral tube feeding can be tried if patients have a functioning gastrointestinal tract. Measures of lean body mass are followed serially. Appetite stimulants have not been shown to prolong life.
Geriatrics Essentials
Normal age-related changes that can contribute to weight loss include the following:
Decreased sensitivity to certain appetite-stimulating mediators (eg, orexins, ghrelin, neuropeptide Y) and increased sensitivity to certain inhibitory mediators (eg, cholecystokinin, serotonin, corticotropin-releasing factor)
A decreased rate of gastric-emptying (prolonging satiety)
Decreased sensitivities of taste and smell
Loss of muscle mass (sarcopenia)
In older people, multiple chronic disorders often contribute to weight loss. Social isolation tends to decrease food intake. Particularly in nursing home patients, depression is a very common contributing factor. It is difficult to sort out the exact contribution of specific factors because of the interactions between factors such as depression, loss of function, drugs, dysphagia, dementia, and social isolation.
When evaluating older patients with weight loss, a useful checklist is of potential contributing factors beginning with the letter D:
Dentition
Dementia
Depression
Diarrhea
Disorders (eg, severe renal, cardiac, or pulmonary disorders)
Drugs
Dysfunction
Dysgeusia
Dysphagia
Older patients who have lost weight should be evaluated for deficiency of vitamin D Vitamin D Deficiency and Dependency Inadequate exposure to sunlight predisposes to vitamin D deficiency. Deficiency impairs bone mineralization, causing rickets in children and osteomalacia in adults and possibly contributing... read more and deficiency of vitamin B12 Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more .
Enteral feeding is rarely beneficial in older patients, except for specific patients in whom such feeding may possibly be a short-term bridge to eating normally.
Key Points
Particularly among nursing home patients, multiple factors commonly contribute to weight loss.
Involuntary weight loss > 5% of body weight or 5 kg warrants investigation.
The highest yield aspects of the evaluation are a thorough history and physical examination.
Advanced imaging or other extensive testing is not usually recommended unless suggested by clinical findings.
Emphasize behavioral measures that encourage eating and try to avoid enteral feeding, particularly in older adults.
