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Involuntary Weight Loss

By Michael R. Wasserman, MD

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Patient Education

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) 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 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 or chronic kidney disease) 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 Vitamin Deficiency, Dependency, and Toxicity) 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.


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.


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 Some Causes of a Presenting Symptom of Involuntary Weight Loss).

With increased appetite, the most common occult causes of involuntary weight loss are

  • Hyperthyroidism

  • Uncontrolled diabetes

  • Disorders that cause malabsorption

With decreased appetite, the most common occult causes of involuntary weight loss are

  • Mental disorders (eg, depression)

  • Cancer

  • Drug adverse effects

  • Drug abuse

Some Causes of a Presenting Symptom of Involuntary Weight Loss


Suggestive Findings

Diagnostic Approach

Endocrine disorders


Increased appetite

Heat intolerance, sweating, tremor, anxiety, tachycardia, diarrhea

Thyroid function tests

Diabetes mellitus, type 1 (new onset or poorly controlled)

Increased appetite

Polydipsia, polyuria

Plasma glucose measurement

Chronic primary adrenal insufficiency

Abdominal pain, fatigue, hyperpigmentation, orthostatic light-headedness

Serum electrolytes, cortisol, and ACTH levels



History of excess consumption

Vascular spiders, Dupuytren's contractures, testicular atrophy, peripheral neuropathy

Sometimes ascites, asterixis

Clinical evaluation

Sometimes liver function tests and/or liver biopsy

  • Of abuse

  • Herbal and OTC products

  • Prescription

History of use

Clinical evaluation

When possible, trial of stopping drug

Mental disorders

Anorexia nervosa

Inappropriate fear of weight gain in an emaciated young woman or adolescent female, amenorrhea

Clinical evaluation


Sadness, fatigue, loss of sexual desire and/or pleasure, sleep disturbance, psychomotor retardation

Clinical evaluation

Renal disorders*

Chronic kidney disease

Edema, nausea, vomiting, stomatitis, dysgeusia, nocturia, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, peripheral neuropathy, seizures

Serum BUN and creatinine measurement

Nephrotic syndrome

Edema, hypertension, proteinuria, fatigue, frothy urine

24-h Urinary protein measurement

Alternatively, spot urinary/serum protein ratio


Fungal infections (usually primary fungal infections)

Fever, night sweats, fatigue, cough, dyspnea

Often risk of exposure based on geography

Sometimes other organ-specific manifestations

Usually cultures and stains

Sometimes serologic tests

Sometimes biopsy

Helminthic (worm) infections

Fever, abdominal pain, bloating, flatulence, diarrhea, eosinophilia

Usually residence or travel in developing countries

Disorder-specific tests (eg, microscopic examination of stool, culture, serology)


Fever, dyspnea, cough, lymphadenopathy, diarrhea, candidiasis

Blood antibody or antigen testing

Subacute bacterial endocarditis

Fever, night sweats, arthralgias, dyspnea, fatigue, Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, retinal artery emboli, stroke

Often in patients with valvular heart disease or IV drug use

Blood cultures



Fever, night sweats, cough, hemoptysis

Sometimes risk factors (eg, exposure, poor living conditions)

Sputum culture and smear

Other systemic disorders


Often night sweats, fatigue, fever

Sometimes bone pain at night or other organ-specific symptoms

Organ-specific evaluation

Giant cell arteritis

Headache, muscle pains, jaw claudication, fever, and/or visual disturbances in an older adult

ESR and, if elevated, temporal artery biopsy


Cough, dyspnea, crackles

Fever, fatigue, lymphadenopathy

Sometimes symptoms of other organ involvement (eg, ocular, hepatic, GI, bone)

Chest x-ray

Sometimes chest CT


Dental and taste disorders

Dysgeusia (loss of taste)

Usually risk factors (eg, cranial nerve dysfunction, use of certain drugs, aging)

Clinical evaluation

Poor dentition

Tooth or gum pain

Halitosis, periodontitis, missing and/or decayed teeth

Clinical evaluation

*Accumulation of edema may mask loss of lean body weight.

Drugs and Herbal Products That Can Cause Weight Loss



Prescription drugs

Antiretroviral drugs, cancer chemotherapy drugs, digoxin, exenatide, levodopa. liraglutide, metformin, NSAIDs, SSRIs, topiramate, zonisamide

Withdrawal after chronic high-dose psychotropic drugs

Herbal products and OTC drugs

Aloe, caffeine, cascara, chitosan, chromium, dandelion, ephedra, 5-hydroxytryptophan, garcinia, guarana, guar gum, glucomannan, herbal diuretics, ma huang, pyruvate, St. John's wort, yerba mate

Drugs of abuse

Alcohol, amphetamines, cocaine, opioids

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: GI tract surgery and cystic fibrosis

  • Chronic inflammatory disorders: Severe RA

  • Gastrointestinal disorders: Achalasia, 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: 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 and heart failure, accumulation of edema may mask loss of lean body weight.


Evaluation focuses on detection of otherwise occult causes. Because these are numerous, evaluation must be comprehensive.


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, OTC 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) is calculated (see Obesity : Diagnosis). Triceps skinfold thickness and mid upper arm circumference can be measured to estimate lean body mass (see Overview of Undernutrition : Physical examination). 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 Interpretation of Selected Findings in Involuntary Weight Loss. 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).

Pearls & Pitfalls

  • When a chronic disease has been stable, do not assume that it is the cause of acute weight loss.

Interpretation of Selected Findings in Involuntary Weight Loss


Some Causes to Consider


Adrenal insufficiency, cancer, chronic kidney disease, depression, infections, giant cell arteritis, nephrotic syndrome, sarcoidosis

Fever, night sweats

Cancer, infections, giant cell arteritis


Infections, cancer, sarcoidosis

Rectal bleeding, abdominal pain

Colorectal cancer

Cough, dyspnea, hemoptysis

Lung cancer, TB, sarcoidosis, fungal pneumonias, HIV/AIDS


Renal or prostate cancer

Heat intolerance, tremor, anxiety, sweating


Polydipsia, polyuria


Bone pain (eg, unrelated to activity, prominent at night)

Cancer (eg, multiple myeloma, bone metastases from breast, prostate, or lung cancer)

Headache or visual symptoms and muscle pains in an older adult

Giant cell arteritis


Endocarditis, giant cell arteritis

Abdominal pain, fatigue, orthostatic light-headedness

Adrenal insufficiency

Abdominal pain

Adrenal insufficiency, diabetes, helminthic infections


Alcoholism, nephrotic syndrome


Chronic kidney disease, nephrotic syndrome


Cancer, infections, inflammatory disorders

Sleep disturbance, loss of libido, sadness



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

  • CBC with differential count

  • ESR or C-reactive protein

  • HIV testing

  • Serum chemistries (serum electrolytes, calcium, hepatic and renal function tests)

  • 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 mo 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.


The underlying disorder is treated. If an underlying disorder causes undernutrition and is difficult to treat, nutritional support should be considered (see Nutritional Support). 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 GI 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 the elderly, 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 elderly 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

Elderly patients who have lost weight should be evaluated for deficiencies of vitamins D (see Vitamin D Deficiency and Dependency) and B12 (see Vitamin B 12 Deficiency).

Enteral feeding is rarely beneficial in elderly 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 the elderly.

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* This is the Professional Version. *