Quality Ratings: The preponderance of data supporting guidance statements are derived from:
level 1 studies, which meet all of the evidence criteria for that study type;
level 2 studies, which meet at least one of the evidence criteria for that study type; or
level 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus.
Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.html
Disclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position of the American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete.
Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the most
current available.
CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1
CreditTM. Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has been
developed for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completion
of the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthen
their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Mai Mahmoud, MBBS, FACP, current
author of this module, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device
manufacturers, or health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical
companies, biomedical device manufacturers, or health-care related organizations.
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Involuntary Weight Loss View online at http://pier.acponline.org/physicians/diseases/d244/d244.html
Module Updated: 2012-05-23
CME Expiration: 2015-05-23
Author
Mai Mahmoud, MBBS, FACP
Table of Contents
1. Screening ..........................................................................................................................2
2. Diagnosis ..........................................................................................................................4
3. Consultation ......................................................................................................................8
4. Hospitalization ...................................................................................................................9
5. Therapy ............................................................................................................................10
6. Patient Education ...............................................................................................................13
7. Follow-up ..........................................................................................................................14
References ............................................................................................................................15
Glossary................................................................................................................................18
Tables ...................................................................................................................................19
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1. Screening Top
Screen all patients for IWL.
1.1 Identify patients who meet the criteria for IWL.
Recommendations
• Weigh patient at each visit and compare current with previous weight.
• Identify patients with sustained IWL ≥ 5% of body weight over a 6-month period, or 10% over a 1-
year period.
Evidence
• A cohort study of the effect of weight loss in community-dwelling patients with Alzheimer's disease
(414 patients with MMSE score between 10 and 26) showed weight loss was associated with rapid
cognitive decline in that cohort (1).
• The National Health and Nutrition Examination Survey found that among older women (ages 60 to
74), weight loss was associated with a two-fold increase in the risk for mobility disability compared
with weight-stable women. These data were adjusted for age, smoking status, educational level,
time to follow-up, and past body mass index (2).
• A cohort study of 247 community-dwelling veterans found a 13% annual incidence of clinically
important weight loss. Mortality rates at 2 years were 28% among those participants with IWL and
11% among those without IWL. There was a greater than two-fold risk for death among those
participants with IWL when the data were adjusted for age, body mass index, cigarette use, other
health status, and laboratory measures (3).
• A summary study of long-term effects of change in body weight on death from all causes included
13 studies from 11 diverse populations, 7 from the U.S., 4 from Europe. The studies suggest that
the highest death rates are found in adults who have lost weight or gained excessive weight (4).
• A 2011 cohort study of 3834 men over 7 years found that weight loss was associated with
increased all-cause mortality compared with no change in weight (RR, 1.49 [CI, 1.17 to 1.89]) (5).
A post-hoc analysis of a randomized, controlled trial in 5202 patients with type 2 diabetes found an
association between weight loss and increased total and cardiovascular mortality (6).
• A study of 4869 British men aged 56 to 75 drawn from general practices found an increased all-
cause mortality risk associated with IWL after adjustment for lifestyle characteristics and
preexisting disease (adjusted RR, 1.71 [CI, 1.33 to 2.19]) (7).
Rationale
• IWL is common and is associated with significant illness and death.
1.2 Identify patients with sustained voluntary weight loss.
Recommendations
• Maintain a level of concern for patients who lose and maintain weight loss voluntarily, especially if
relative sarcopenia is noted.
• Encourage supervised voluntary weight loss programs for overweight and obese patients.
Evidence
• Studies have been inconclusive in associating voluntary weight loss and increased mortality (6, 8,
9, 10, 11).
• A one-year randomized controlled trial evaluated the effect of voluntary weight loss in the elderly
by diet, exercise, or both, and showed significant improvement in physical function and frailty (11).
• The ADAPT study concluded that voluntary weight loss in older adults was not associated with
increased mortality and may reduce mortality risk (9).
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• A cohort study of 247 community-dwelling veterans found that the 2-year mortality rate among
persons who voluntarily lost weight was 36%. This mortality rate was higher than that experienced
by participants with IWL.(3).
• A study of 4869 British men aged 56 to 75 drawn from general practices found an increased all-
cause mortality risk associated with IWL after adjustment for lifestyle characteristics and
preexisting disease (adjusted RR, 1.71 [CI, 1.33 to 2.19]). However, intentional weight loss in this
study was associated with a significant benefit in all-cause mortality (RR, 0.59 [CI, 0.34 to 1.00]),
with the benefit most apparent in markedly overweight men with body mass index ≥28 kg/m2 (7).
Rationale
• Whether the observed weight loss is voluntary or unintentional is difficult to determine.
• Voluntary weight loss, even if it targets excess fat, may include accelerated muscle loss, which
adversely affects functional status in elderly patients.
• Older observational studies suggested an association between voluntary weight loss and an
increase in mortality and morbidity, but this finding has not been validated by new studies.
Comments
• The evidence regarding intentional and unintentional weight loss and their physiologic effects is
inconsistent and remains an unresolved issue, as it is often difficult to distinguish between
intentional and unintentional weight loss in these studies (7; 12; 13; 14; 15). However, more
recent studies have shown favorable outcomes of weight loss in the elderly.
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2. Diagnosis Top
Confirm the diagnosis of IWL and understand the likelihood before evaluation of specific causes; then perform a careful history and physical exam to identify the cause.
2.1 Use objective measures of weight loss to confirm the diagnosis.
Recommendations
• Use documented weights or objective evidence of weight loss, such as change in fit of clothes or
corroboration by trusted observer, before pursuing a work-up of IWL.
• Screen at-risk patients for adequate caloric intake by using a screening tool like the Mini Nutritional
Assessment-Short Form.
• Body mass index can be limited by error in height measurement because of kyphosis, which is
common in the elderly.
Evidence
• Almost one-half of patients initially enrolled in a cohort study of IWL had not lost weight (16).
• Early screening has the potential to identify either nutritional risk or nutritional decline in older
adults (17; 18).
Rationale
• Many patients who report IWL in fact have not lost weight.
• The cause may simply be inadequate caloric intake for social reasons, which invalidates the need
for comprehensive investigations.
2.2 Confirm that changes in total body water are not the cause of IWL.
Recommendations
• Evaluate volume status and weight serially.
• Be attentive to muscle mass, and look for loss of muscle mass in obese patients with intentional
weight loss.
Evidence
• Consensus.
Rationale
• Dramatic weight changes can occur with gain or loss of total body water. These changes often
occur more quickly and erratically than changes in lean body mass, which is often gradual and
sustained.
• Obesity can mask the development of loss of muscle mass (sarcopenia), which has a negative
effect on functional status.
Comments
• The assessment of weight change due to gain or loss of total body water will often be made on
clinical grounds such as in a patient with congestive heart failure and recent increase in diuretic
dose or a patient with diabetes and uncontrolled blood glucose levels experiencing significant
osmotic diuresis.
2.3 Understand the likelihood of IWL in specific settings before evaluating its
cause.
Recommendations
• Understand the common causes of IWL, which are in four major categories:
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Psychiatric diseases including depression, which may be the cause in 10% to 20% of patients
Malignancy
Chronic inflammatory conditions or infections
Metabolic causes, commonly hyperthyroidism or uncontrolled diabetes
• Ask about:
Substance abuse and smoking, which may be associated with a physical cause of unintentional weight loss
Gastrointestinal symptoms such as nausea or vomiting, diarrhea, dysphagia, or bleeding
Oral health
A general medical history to look for new or worsening chronic illnesses and signs of potential malignancy
Current and recent medication use
Symptoms suggesting dementia in older patients
Endocrine symptoms, including menstrual irregularities
• Take a careful social history, since social isolation, poverty, and immobility can lead to IWL.
• Perform a complete physical exam, looking for signs of malignancy, and consider screening for
depression or dementia.
• See table Differential Diagnosis of Involuntary Weight Loss.
• See table Studies of Involuntary Weight Loss: Basic Patient Characteristics and Causes.
Evidence
• The most common causes belong to four major categories: malignancy; chronic infections or
inflammation, especially gastrointestinal; metabolic, such as hyperthyroidism; and psychiatric.
Other causes are drugs, social factors, and age-related (19).
• In some patients, more than one of these causes is responsible (19).
• A small prospective study of patients with unintentional weight loss found that the following factors
were associated with a physical cause of IWL: fatigue, smoking (>20 pack-year history), nausea or
vomiting, change in cough, and increased appetite (16).
• Cancer is the most common physical cause of IWL and gastrointestinal causes are the second most
common physical cause (16, 20, 21).
• Many medicines can cause IWL by inducing anorexia, dysgeusia, gastrointestinal symptoms, dry
mouth, confusion or inattention, or a movement disorder. These can be caused by antibiotics,
anticholinergic agents, antiparkinsonian agents, digoxin, iron supplements, NSAIDs, opiates,
potassium supplements, SSRIs, theophylline preparations, and thyroid hormone supplementation
(22; 23).
• A study of 100 VA patients evaluated on a geriatric rehabilitation unit found that the number of
general oral problems was the best predictor of IWL within 1 year of admission (24). A study of
563 community-dwelling adults aged 70 and older found that approximately one-third lost 4% or
more of their body weight. Edentulousness, female gender, and advanced age were independently
associated with IWL (25).
• Social isolation, poverty, and immobility are associated with functional IWL (26), and insomnia has
been associated with weight loss (27).
• Ask about memory loss, aphasia, apraxia, anomia, and problems with executive function. IWL is
associated with dementia and may precede diagnosis of the dementia (28).
Rationale
• There have been few studies on the relative prevalence of various causes of IWL; however, these
studies have been consistent in the proportion of patients with various causes.
Comments
• Although studies are consistent in distribution of causes for IWL, they are all subject to substantial
referral bias. Involuntary weight loss is common among community-dwelling older adults. A
community-based study of 563 adults age 70 and older found that approximately one third of the
sample lost 4% or more of their previous total body weight, and 6% of men and 11% of women
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lost 10% or more of their body weight. In this sample, dentate status was a strong risk factor for
IWL. Such data suggest that in nonselected populations, both other and unknown causes of
individual weight loss may be more common than those seen in the previously cited studies (25).
In addition, in an analysis of National Health and Nutritional Examination Survey data, 13% of the
population reported recent IWL, with 6.9% reporting recent IWL ≥5% (29).
2.4 Understand that the cause of IWL among nursing home residents may be different from the noninstitutionalized population.
Recommendations
• Consider undernutrition, depression, medications, dehydration, and issues related to dementia in
the diagnosis of IWL in nursing home residents.
Evidence
• Undernutrition due to inadequate feeding is one of the major causes of weight loss in nursing home
residents (30; 31).
• A study of residents in a community nursing home found depression to account for IWL in 60% of
residents who stayed in the nursing home for less than 6 months and in 36% of residents who
stayed more than 6 months (32).
• A retrospective chart review at a tertiary care VA hospital found that the frequency and degree of
weight loss in medically ill elderly patients taking fluoxetine should be studied further (33).
• A review discusses the clinical implications of the aging heart (34).
• The complicated issues associated with IWL in elderly outpatients are outlined in a review (22).
• Common problems causing failure to thrive in the elderly are the focus of this article (23).
Rationale
• These conditions commonly cause IWL in nursing home residents.
Comments
• The study of residents in a community nursing home (32) had certain methodologic flaws; further
studies in this area are necessary.
2.5 Limit diagnostic testing to a set of basic studies unless history and
physical exam suggest a specific physical cause of IWL requiring additional testing.
Recommendations
• Consider obtaining the following if the cause of the weight loss is not clear:
Complete blood count
Erythrocyte sedimentation rate or C-reactive protein
Serum chemistry tests, including calcium and liver function
HIV test
Thyroid-stimulating hormone level
Urinalysis
Chest radiograph
Stool occult blood
• In patients with gastrointestinal symptoms, also consider upper gastrointestinal series, abdominal
ultrasonography, abdominal CT scan, or esophagogastroduodenoscopy.
• See table Laboratory and Other Studies for Involuntary Weight Loss.
Evidence
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• In a study of 45 elderly patients with IWL, 10 CT scans were performed on 5 patients. These CT
scans offered no further information except in 1 patient in whom the CT scan localized a
malignancy that had been previously suspected on plain radiographs (21).
• In other studies in which a cause of IWL was aggressively pursued, thorough history and physical
exam and basic laboratory testing, rather than advanced imaging, provided the diagnosis in nearly
all patients (16; 20; 22; 35).
• A study of asymptomatic IWL at a tertiary referral center in Spain found that, among those
patients ultimately diagnosed with cancer (n=104), the following were the most useful follow-up
tests to make a diagnosis: for patients who had only an isolated abnormality in the CBC (n=39),
abdominal CT scan (n=12), abdominal ultrasonography (n=9), and endoscopy (n=8); for patients
who had only an isolated abnormality in liver function tests (n=52), abdominal ultrasonography
(n=40) and abdominal CT scan (n=9); and for patients who had normal liver function tests and
CBC (n=13), upper endoscopy (n=5), and abdominal CT scan (n=5) (36).
Rationale
• Body imaging of the thorax and abdomen with CT or MRI in the absence of historical information or
physical exam findings pointing to the thorax or abdomen has not been shown to help determine
the cause of IWL.
Comments
• The work-up should be tailored to the needs and status of the individual patient.
2.6 Recognize the broad differential diagnosis underlying IWL.
Recommendations
• Recognize the pretest likelihood of different causes of IWL, and use the clinical evaluation and
selected laboratory studies to narrow the differential diagnoses.
• See table Differential Diagnosis of Involuntary Weight Loss.
Evidence
• The most common physical cause of IWL is malignancy. The second most common physical cause
is benign gastrointestinal disease. A broad spectrum of conditions accounts for the remainder of
physical causes (16; 20; 21; 36; 38).
• Although these studies are consistent in distribution of causes of IWL, they are all subject to
substantial referral bias. A community-based study of 563 adults age 70 and older found that
approximately one third of the sample lost 4% or more of their previous total body weight, and 6%
of men and 11% of women lost 10% or more of their body weight. In this sample, dentate status
was a strong risk factor for IWL. Such data suggest that in nonselected populations, both other and
unknown causes of IWL may be more common than those seen in the studies cited above (25).
Rationale
• Although certain causes are more common, it is often difficult to establish a definitive diagnosis.
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3. Consultation Top
Consider consultation for diagnosis based on the specific findings. Consider consultation to address management of the underlying cause of IWL.
3.1 Refer patients to appropriate specialists for evaluation only when specific
clinical problems underlying weight loss are identified.
Recommendations
• Refer patients with abnormal findings on oral exam to a dentist.
• Consider consultation when a specific cause is clear, such as oncology in the patient with cancer or
gastroenterology in the patient with a gastrointestinal cause requiring specific diagnostic testing or
management.
• Conduct a careful follow-up with repeated careful history, physical exam, and basic laboratory
work-up for patients in whom a cause for IWL cannot be determined by an initial work-up.
Evidence
• Studies suggest that if a physical cause of IWL is to be diagnosed after initial work-up, it will
become apparent within 6 months of the initial evaluation (16).
Rationale
• Approximately 25% of patients will not have a discernable cause found after appropriate work-up
and long-term follow-up.
3.2 Obtain consultation for help in managing patients with IWL with selected
problems.
Recommendations
• When appropriate, consider:
Dental consultation for all patients with oral problems such as loose teeth, caries, or poorly fitting or painful dentures
Oncology and gastrointestinal specialty consultation to manage specific causes of IWL
Psychiatric consultation for patients with depression or anxiety disorders not amenable to treatment by their primary care physician
Social work consultation for social issues related to IWL
Occupational or physical therapy to address functional issues related to IWL
Geriatrics medicine consultation for older persons with IWL
Evidence
• Mainly consensus.
• With regard to dental consultation, a study of older community-dwelling adults found that
edentulousness was independently associated with IWL. Although there are no specific data to
prove that improving dental care will alleviate IWL, it is reasonable to attempt to correct dental
problems (25).
Rationale
• Certain causes of IWL may require subspecialty management.
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4. Hospitalization Top
Recognize that hospitalization for IWL is rarely required except for certain underlying causes.
4.1 Hospitalize patients who are volume-depleted and who cannot consume fluids or for reasons related to the primary condition.
Recommendations
• Hospitalize patients who are volume depleted and unable to consume oral fluids or for whom
treatment of the primary condition may result in improved ability to take fluids and food.
Evidence
• Consensus.
Rationale
• Given the broad differential diagnosis for IWL and the fact that a specific condition may not always
be apparent, decisions about hospitalization must be made on an individual basis.
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5. Therapy Top
Direct therapy for involuntary weight loss at its underlying cause.
5.1 Treat the presumed cause of IWL.
Recommendations
• Once a presumed specific diagnosis of the cause of IWL is made, anticipate that treatment of that
condition should, in most patients, alleviate the IWL.
• If the patient continues to lose weight involuntarily, recognize that the presumed diagnosis may
not be related to IWL.
Evidence
• Consensus.
Rationale
• Involuntary weight loss may or may not necessarily be related to an identifiable underlying disease
process.
5.2 Consider medication and lifestyle changes for some patients.
Recommendations
• Change or eliminate medications that may be associated with anorexia or temporally related to the
IWL.
• Address issues of social isolation and poor eating environments, if applicable.
• Ensure that the patient's oral health is adequate.
• Ensure the patient has access to food, how the patient gets food, the kind of food chosen, and
whether the patient is able to eat it.
• Assist patients who need help with eating by seeking to improve their functional status in order to
allow adequate intake of food.
• Eliminate restrictive diets, when appropriate.
• Suggest flavor enhancement of food to help improve dietary intake.
• Consider recommending resistance training in select patients, such as those with AIDS wasting
syndrome.
Evidence
• Data in this area are scarce. One trial showed that flavor enhancement of food improves dietary
intake and nutritional status of elderly nondemented nursing home residents (39).
• In a small randomized trial of patients with AIDS wasting syndrome, progressive resistance training
was associated with improved physical function and quality of life when compared with treatment
with oxandrolone or nutrition alone (40).
• Consensus is that these specific recommendations may be helpful, especially in older persons (26).
• In a longitudinal cohort study of community-dwelling elderly individuals, there was a linear
relationship between the number of medications used and the risk for weight loss (41).
Rationale
• Simple measures unrelated to any specific underlying disease process may be helpful and are often
overlooked.
5.3 Recognize the limited proven benefit of oral nutritional supplementation
in patients with IWL.
Recommendations
• Consider oral supplementation, but do not expect it necessarily to reverse IWL.
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• Note that nutritional supplementation may be useful for those patients for whom access to calories
is an issue because of functional impairments.
• Do not institute enteral feeding, since it provides no survival benefit and may lead to complications.
Evidence
• A meta-analysis of protein and energy supplementation in older persons, not focused on
populations with involuntary weight loss, noted the poor quality of most of the trials included in the
analysis, particularly with regard to blinding. With those caveats, the analysis found that mortality
was reduced with protein and energy supplementation, although the decrease was of borderline
statistical significance, and that this was limited to patients given oral supplementation in the
hospital and possibly in long-term care, but not in the community. However, effects on mortality
and morbidity cannot be generalized for all older patients and care settings (42).
• There are a number of studies of the effects of nutritional supplementation in frail older persons
and nursing home patients. The provision of an oral protein/calorie liquid supplement is a common
strategy in these studies. Results have been inconsistent. Modest weight gain is shown in some
studies (43), while weight loss or no change in weight is shown in others (44; 45).
• A randomized controlled trial examined the effect of nutritional supplementation in frail older adults
(age 70 or above) without IWL in the long-term care setting who could walk more than 6 meters at
baseline. Nutritional supplementation of 360 kcal/d resulted in a small weight gain (mean 0.8 kg)
compared with placebo. The nutritional supplementation blunted normal eating. There was no
effect on mobility, muscle strength, or physical activity (46).
• Flavor enhancement of food may be associated with modest gains in body weight in older nursing
home patients (39). This strategy has not been studied in patients with IWL.
• Nutritional supplementation provided by enteral feeding tubes provides no survival benefit (47).
Rationale
• Reversal of IWL most often depends on treatment of a true underlying cause.
Comments
• There are no controlled data on nutritional supplementation in patients with IWL per se.
5.4 Recognize that appetite stimulants are of limited benefit for patients with IWL who do not respond to treatment of the primary cause or is of unknown
cause.
Recommendations
• Avoid prescribing appetite stimulants for patients with IWL.
• Recognize that studies of both megestrol acetate, usually at a dose of 800 mg/day, and
thalidomide, which is restricted in the U.S., have not shown benefit, and both drugs are associated
with substantial side effects.
• Consider using mirtazapine to treat depression in patients with depression and weight loss.
Evidence
• Appetite stimulant therapy for IWL has been studied mainly in patients with AIDS or cancer
cachexia. In these patients, certain agents have been shown to promote weight gain; however, a
survival advantage has not been shown (48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61),
and in some trials, in patients who received such agents, there may have been an increased death
rate (48; 49).
• A review of 15 trials of megestrol showed that appetite was improved in most trials, and that
quality of life improved in only 2 of 11 trials (62).
• In a randomized, controlled trial of 50 patients with inoperable pancreatic cancer, patients treated
with thalidomide lost 0.06 kg compared with 3.62 kg in the placebo group. There were no
differences in survival, functional status, or quality of life among the patients taking thalidomide.
However, there were significant side effects in the treatment group, including peripheral
neuropathy, somnolence, and rash (61).
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• While mirtazapine results in weight gain in patients with depression, it has not been studied in
nondepressed patients and should not be used to treat weight loss in the absence of depression
(63).
Rationale
• Appetite stimulant therapy does not offer a survival advantage.
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6. Patient Education Top
Provide patients with information about their condition, its treatment, and management.
6.1 Inform patients that IWL requires physician evaluation, that the cause is often detectable and treatable, and that most patients with this condition do
not have cancer.
Recommendations
• Advise patients that:
Involuntary weight loss may be associated with many conditions
The history and physical exam are the most important aspects of the evaluation and that they need to be especially forthcoming with historical information
Laboratory and diagnostic tests may be needed to help diagnose the cause of IWL
The use of advanced imaging techniques such as CT scans and MRI in the absence of a specific indication is not appropriate
If the initial work-up is unrevealing, close medical follow-up for at least 6 months is required
If the initial work-up is normal, it is important to report any new physical or psychiatric symptoms
The prognosis for patients in whom a specific cause of IWL is not found is the same as for those without IWL
Evidence
• Based on data from studies of IWL (16; 20; 21).
Rationale
• A basic understanding of IWL will help the patient deal with the condition and may enhance the
physician's ability to diagnose and treat the patient's IWL.
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7. Follow-up Top
For patients with IWL in whom a cause could not be determined initially, reevaluate at 3 to 6 months.
7.1 Reevaluate patients with IWL of undetermined cause at 3 to 6 months.
Recommendations
• Carefully repeat the history, focusing on any new symptoms that the patient may have.
• Repeat the physical exam, especially those portions dictated by any new history information.
Evidence
• In one cohort of patients, physical causes of IWL were always apparent within 6 months of initial
evaluation (3; 16).
Rationale
• If the initial evaluation is normal, it is reasonable to enter a period of watchful waiting and
reevaluate the patient in 3 to 6 months.
• It is unusual for IWL to be due to serious disease that is occult. If serious disease is present, the
cause is likely to become evident within 3 to 6 months.
• Repeating the history and physical and targeted laboratory exam may uncover a cause of IWL not
apparent at the initial evaluation.
7.2 Identify patients in whom a cause of IWL cannot be determined after appropriate initial and follow-up evaluation at 6 months, and reassure them of
a good prognosis.
Recommendations
• Reassure patients that their prognosis is good and continue to monitor them.
Evidence
• In studies examining the cause of IWL, patients in whom a cause of IWL could not be found after
appropriate initial and follow-up evaluation had the same long-term outcomes as patients without
IWL (16; 21) and significantly better mortality than those with an established cause of weight loss,
independent of whether the cause was malignant or not (38).
Rationale
• It is appropriate at this point to reassure a patient that his or her prognosis is good.
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References Top
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2. Launer LJ, Harris T, Rumpel C, Madans J. Body mass index, weight change, and risk of mobility disability in middle-aged and older women. The epidemiologic follow-up study of NHANES I. JAMA. 1994;271:1093-8. (PMID: 8151851)
3. Wallace JI, Schwartz RS, LaCroix AZ, Uhlmann RF, Pearlman RA. Involuntary weight loss in older outpatients: incidence and clinical significance. J Am Geriatr Soc. 1995;43:329-37. (PMID: 7706619)
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Glossary Top
AIDS acquired immunodeficiency syndrome
CBC complete blood count
COPD chronic obstructive pulmonary disease
CT computed tomography
EGD
esophagogastroduodenoscopy
ESR
erythrocyte sedimentation rate
GI gastrointestinal
HIV human immunodeficiency virus
IWL
involuntary weight loss
MMSE Mini-Mental State Examination
MRI magnetic resonance imaging
NSAID nonsteroidal anti-inflammatory drug
qd once daily
SSRI selective serotonin-reuptake inhibitor
tid three times daily
TSH
thyrotropin
VA Veterans Affairs
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Tables Top
Laboratory and Other Studies for Involuntary Weight Loss
Test Sensitivity (%) Specificity (%) Notes
CBC Abnormal (usually anemia) in 14% with physical
cause of weight loss (16).
Electrolytes, blood urea nitrogen, creatinine,
glucose, liver function tests
In one study, patients with a combination of
decreased albumin and elevated alkaline phosphatase had 17% sensitivity and 87%
specificity for cancer (20). In another study, 22%
patients with physical cause of IWL had abnormal
blood chemistry findings (16). Adrenal
insufficiency was associated with electrolyte
disturbances in 92% of patients (37).
ESR or CRP Examined in one study of persons with IWL (20).
Increased in patients with neoplasia (mean ESR
49) compared with those with psychiatric (mean
ESR 19) and unknown cause (mean ESR 26) of
IWL
Combination of low albumin and elevated alkaline
phosphatase levels
17 87 This combination was 17% sensitive and 87%
specific for neoplasia as a cause of IWL in one study (20)
Thyroid-stimulating hormone To look for hyperthyroidism
Fecal occult blood test
Chest radiography Most useful test in one series with 41% abnormal
among individuals with a physical cause of IWL (16)
HIV
Upper GI series or EGD Upper GI had the highest yield in disclosing a pertinent abnormality among tests beyond basic
screening tests—20% with abnormalities among
persons with physical cause of weight loss, all
with GI symptoms (16).
Abdominal ultrasonography
Abdominal CT scan
CBC = complete blood count; CRP = C-reactive protein; CT = computed tomography; EGD = esophagogastroduodenoscopy; ESR = erythrocyte sedimentation rate; GI = gastrointestinal; HIV = human
immunodeficiency virus; IWL = involuntary weight loss.
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Differential Diagnosis of Involuntary Weight Loss
Disease Characteristics
Cancer Percent of patients with physical cause of IWL: 30%-55%. Percent of all patients with IWL: 16%-38%
(16; 20; 21; 36; 38)
Gastrointestinal disorders Percent of patients with physical cause of IWL: 22%-25%. Percent of all patients with IWL: 10%-18%
(16; 20; 21; 36; 38)
Endocrine disorders Percent of patients with physical cause of IWL: 6%-9%. Percent of all patients with IWL: ~5% (16; 20;
21; 36; 38)
Infections Percent of patients with physical cause of IWL: 6%-9%. Percent of all patients with IWL: ~5% (16; 20;
21; 36; 38)
Pulmonary disorders Percent of patients with physical cause of IWL: 8%. Percent of all patients with IWL: 6% (16; 20; 21;
38)
Medications Percent of patients with physical cause of IWL: 3%-18%. Percent of all patients with IWL: 2%-9% (16;
20; 21)
Cardiovascular diseases Percent of patients with physical cause of IWL: 13%. Percent of all patients with IWL: ~9% (16; 20;
21; 38)
Renal disease Percent of patients with physical cause of IWL: 6%. Percent of all patients with IWL: 4% (16; 20; 21)
Neurologic disease Percent of patients with physical cause of IWL: 2%-13%. Percent of all patients with IWL: 2%-7% (16;
20; 21; 36)
Depression Percent of all patients with IWL: 9%-18% (16; 20; 21; 36; 38)
No diagnosis Percent of all patients with IWL: 5%-26% (16; 20; 21; 36; 38)
IWL = involuntary weight loss.
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Studies of Involuntary Weight Loss: Basic Patient Characteristics and Causes
Study Patients (n) Outpatients (%) Age (y) Cause (%)
Physical Psychiatric Unknown*
16 91 30 59 65 9 26
20 154 0 64 66 10 23
21 45 100 72 58 18 24
36 276 28 66 72 23 5
38 158 0 68 73 11 16
64 50 0 59 48 42 10
* ‘Unknown’ refers to patients in whom no cause of involuntary weight loss could be elicited after history and physical exam, appropriate diagnostic work-up, and long-term follow-up. Adapted from 16; 20; 21.