Involuntary weight loss generally develops over weeks or months. It can be a sign of a significant physical or mental health condition 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 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 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 Overview of Vitamins) may also be present.
The overall incidence of significant involuntary weight loss is approximately 5% per year in the United States. However, incidence increases with aging, up to 20% in the geriatric population and up to 60% among nursing home patients (1). Involuntary weight loss is associated with an increased risk of all-cause and cause-specific (eg, cancer, cardiovascular disease) mortality (2).
References
1. Perera LAM, Chopra A, Shaw AL. Approach to Patients with Unintentional Weight Loss. Med Clin North Am. 2021;105(1):175-186. doi:10.1016/j.mcna.2020.08.019
2. Hussain SM, Newman AB, Beilin LJ, et al. Associations of Change in Body Size With All-Cause and Cause-Specific Mortality Among Healthy Older Adults. JAMA Netw Open. 2023;6(4):e237482. Published 2023 Apr 3. doi:10.1001/jamanetworkopen.2023.7482
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 often, but not always, 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 (see also Pathways Regulating Food Intake).
Etiology of Involuntary Weight Loss
Many diseases 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).
With increased appetite, the most common occult causes of involuntary weight loss are
Uncontrolled diabetes
Disorders that cause malabsorption
With decreased appetite, the most common occult causes of involuntary weight loss are
Mental health conditions (eg, depression)
Some Causes of a Presenting Symptom of Involuntary Weight Loss
Cause | Suggestive Findings | Diagnostic Approach |
|---|---|---|
Endocrine disorders | ||
Increased appetite Heat intolerance, sweating, tremor, anxiety, tachycardia, diarrhea | Thyroid function tests | |
Diabetes mellitus (new onset or poorly controlled) | Increased appetite Polydipsia, polyuria | Plasma glucose measurement |
Chronic primary adrenal insufficiency | Abdominal pain, fatigue, hyperpigmentation, orthostatic lightheadedness | Serum electrolytes, cortisol, and adrenocorticotropic hormone levels |
Medications and Drugs | ||
History of excess consumption Vascular spiders, Dupuytren contractures, testicular atrophy, peripheral neuropathy Sometimes ascites, asterixis | Clinical evaluation Liver tests | |
Medications and Drugs
| History of use | Clinical evaluation Drug screen for drugs of abuse When possible, trial of stopping medication |
Mental health conditions | ||
Inappropriate fear of weight gain in an underweight adolescent or young adult, amenorrhea | Clinical evaluation | |
Sadness, fatigue, loss of sexual desire and/or pleasure, sleep disturbance, psychomotor retardation | Clinical evaluation | |
Renal disorders* | ||
Edema, nausea, vomiting, stomatitis, dysgeusia, nocturia, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, peripheral neuropathy, seizures | Serum blood urea nitrogen (BUN) and creatinine measurement | |
Edema, hypertension, proteinuria, fatigue, frothy urine | 24-hour urinary protein measurement Alternatively, spot urinary/serum protein ratio | |
Infections | ||
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 |
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 | |
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 Echocardiography | |
Fever, night sweats, cough, hemoptysis Sometimes risk factors (eg, exposure, poor living conditions) | Chest radiograph Sputum culture and smear PPD and/or interferon-gamma release assay | |
Other systemic disorders | ||
Often night sweats, fatigue, fever Sometimes bone pain at night or other organ-specific symptoms | Organ-specific evaluation | |
Headache, muscle pains, jaw claudication, fever, and/or visual disturbances in an older adult | ESR and/or CRP; if elevated, temporal artery ultrasound or biopsy | |
Cough, dyspnea, crackles Fever, fatigue, lymphadenopathy Sometimes symptoms of other organ involvement (eg, ocular, hepatic, gastrointestinal, bone) | Chest radiograph Sometimes chest CT Biopsy | |
Dental and taste disorders | ||
Dysgeusia (loss of taste) | Usually risk factors (eg, cranial nerve dysfunction, use of certain medications, 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. CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; PPD = purified protein derivative | ||
Medications and Herbal Products That Can Cause Weight Loss
Category | Examples |
|---|---|
Prescription medications | Antiretroviral medications, cancer chemotherapy medications, digoxin, exenatide, levodopa, liraglutide, metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), topiramate, zonisamide Withdrawal after chronic high-dose psychotropic medications |
Herbal products and over-the-counter medications | Aloe, berberine, 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:
Chronic inflammatory diseases: Severe rheumatoid arthritis, progressive systemic sclerosis
Gastrointestinal diseases: Achalasia, celiac disease, Crohn disease, chronic pancreatitis, esophageal obstructive disorders, ischemic colitis, diabetic enteropathy, peptic ulcer disease, ulcerative colitis (late)
Some malabsorptive diseases: Gastrointestinal tract surgery and cystic fibrosis
Severe, chronic heart and lung diseases: Chronic obstructive pulmonary disease (COPD), heart failure (stage III or IV), restrictive lung disease
Mental health conditions (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 of Involuntary Weight Loss
Evaluation focuses on detection of otherwise occult causes. Because these are numerous, evaluation must be comprehensive (1).
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 and social history may reveal a disease capable of causing weight loss. Also addressed should be use of prescription medications, over-the-counter medications, 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 ability to prepare meals, financial circumstances, loss of communal eating routine).
Physical examination
Vital signs may reveal fever, tachycardia, tachypnea, and hypotension. Weight and height are measured and body mass index (BMI) is calculated; the addition of a waist circumference measurement allows calculation of the body roundness index (BRI) (2). Triceps skinfold thickness and mid upper arm circumference can be measured to estimate lean body mass. 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 adult
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. Abnormal findings suggest the cause of weight loss in approximately 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 the existing 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
|
Interpretation of Selected Findings in Involuntary Weight Loss
Finding | Some Causes to Consider |
|---|---|
Fatigue | Adrenal insufficiency, cancer, chronic kidney disease, depression, infections, giant cell arteritis, nephrotic syndrome, sarcoidosis |
Fever, night sweats | Cancer, infections, giant cell arteritis |
Lymphadenopathy | Infections, cancer, sarcoidosis |
Rectal bleeding, abdominal pain | Colorectal cancer |
Cough, dyspnea, hemoptysis | Lung cancer, tuberculosis, sarcoidosis, fungal pneumonias, HIV/late stage HIV |
Hematuria | Renal, bladder, or prostate cancer |
Heat intolerance, tremor, anxiety, sweating | Hyperthyroidism |
Polydipsia, polyuria | Diabetes mellitus or arginine vasopressin deficiency (previously central diabetes insipidus) |
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 |
Arthralgias | Endocarditis, giant cell arteritis, chronic hepatitis |
Abdominal pain, fatigue, orthostatic lightheadedness | Adrenal insufficiency |
Abdominal pain | Adrenal insufficiency, diabetes, helminthic infections, gastrointestinal tract cancers |
Ascites | Alcohol use disorder, nephrotic syndrome, cancer (eg, ovarian, gastrointestinal) |
Edema | Chronic kidney disease, nephrotic syndrome |
Fever | Cancer, infections, inflammatory disorders |
Sleep disturbance, loss of libido, sadness | Depression |
Testing
Age-appropriate cancer screening (eg, colonoscopy, mammography) is indicated if not previously performed. Other testing is performed 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 radiograph
Urinalysis
Complete blood count (CBC) with differential count
Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
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 approximately 1 month that includes a weight measurement. A referral to a dietician would be appropriate. 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.
Evaluation references
1. Gaddey HL, Holder KK. Unintentional Weight Loss in Older Adults. Am Fam Physician. 2021;104(1):34-40.
2. Zhang X, Ma N, Lin Q, et al. Body Roundness Index and All-Cause Mortality Among US Adults [published correction appears in JAMA Netw Open. 2024 Jul 1;7(7):e2426540. doi: 10.1001/jamanetworkopen.2024.26540]. JAMA Netw Open. 2024;7(6):e2415051. Published 2024 Jun 3. doi:10.1001/jamanetworkopen.2024.15051
Treatment of Involuntary Weight Loss
The underlying disorder is treated.
If an underlying disorder causes undernutrition and is difficult to treat, additional nutritional support 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 at each sitting.
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 in cancer patients (1).
Treatment reference
1. Childs DS, Jatoi A. A hunger for hunger: a review of palliative therapies for cancer-associated anorexia. Ann Palliat Med. 2019;8(1):50-58. doi:10.21037/apm.2018.05.08
Geriatrics Essentials: Involuntary Weight Loss
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 adults, multiple chronic disorders often contribute to weight loss. Dental problems (eg, periodontitis) become more common with aging and can compromise nutrient intake and digestion. 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, medications, dysphagia, dementia, and social isolation.
When evaluating older adults 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 adults who have lost weight should be evaluated for deficiency of vitamin D and deficiency of vitamin B12.
Enteral (tube) feeding is rarely beneficial in older adults, except for specific patients in whom such feeding may possibly be a short-term bridge to eating normally.
Key Points
Multiple factors commonly contribute to weight loss, particularly among nursing home patients.
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.
