involuntary weight loss · involuntary weight loss pier is copyrighted ©2013 by the american...

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.

PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.

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

http://pier.acponline.org/physicians/diseases/d244/d244.html

Involuntary Weight Loss


of 21

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).



of 21

• 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.



of 21

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:



of 21

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



of 21

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



of 21

• 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.



of 21

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.



of 21

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.



of 21

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.



of 21

• 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).



of 21

• 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.



of 21

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.



of 21

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.



of 21

References Top

1. Soto ME, Secher M, Gillette-Guyonnet S, Abellan van Kan G, Andrieu S, Nourhashemi F, et al. Weight loss and rapid cognitive

decline in community-dwelling patients with Alzheimer's disease. J Alzheimers Dis. 2012;28:647-54. (PMID: 22045479)

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)

4. Andres R, Muller DC, Sorkin JD. Long-term effects of change in body weight on all-cause mortality. A review. Ann Intern Med. 1993;119:737-43. (PMID: 8363208)

5. Chipkin SR. Weight and weight change-think about the context. Am J Med. 2011;124:891-2. (PMID: 21962307)

6. Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, et al. Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: An analysis of the PROactive study population. Int J Cardiol. 2012;162:20-6. (PMID: 22037349)

7. Wannamethee SG, Shaper AG, Lennon L. Reasons for intentional weight loss, unintentional weight loss, and mortality in older men. Arch Intern Med. 2005;165:1035-40. (PMID: 15883243)

8. Frimel TN, Sinacore DR, Villareal DT. Exercise attenuates the weight-loss-induced reduction in muscle mass in frail obese older adults. Med Sci Sports Exerc. 2008;40:1213-9. (PMID: 18580399)

9. Shea MK, Houston DK, Nicklas BJ, Messier SP, Davis CC, Miller ME, et al. The effect of randomization to weight loss on total mortality in older overweight and obese adults: the ADAPT Study. J Gerontol A Biol Sci Med Sci. 2010;65:519-25. (PMID: 20080875)

10. Shea MK, Nicklas BJ, Houston DK, Miller ME, Davis CC, Kitzman DW, et al. The effect of intentional weight loss on all-cause mortality in older adults: results of a randomized controlled weight-loss trial. Am J Clin Nutr. 2011;94:839-46. (PMID: 21775558)

11. Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011;364:1218-29. (PMID: 21449785)

12. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in overweight white men aged 40-64 years. Am J Epidemiol. 1999;149:491-503. (PMID: 10084238)

13. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40-64 years. Am J Epidemiol. 1995;141:1128-41. (PMID: 7771451)

14. French SA, Folsom AR, Jeffery RW, Williamson DF. Prospective study of intentionality of weight loss and mortality in older women: the Iowa Women's Health Study. Am J Epidemiol. 1999;149:504-14. (PMID: 10084239)

15. Sørensen TI. Weight loss causes increased mortality: pros. Obes Rev. 2003;4:3-7. (PMID: 12608522)

16. Marton KI, Sox HC Jr, Krupp JR. Involuntary weight loss: diagnostic and prognostic significance. Ann Intern Med. 1981;95:568-74. (PMID: 7294545)

17. Jürschik P, Torres J, Solá R, Nuin C, Botigué T, Lavedán A. High rates of malnutrition in older adults receiving different levels of health care in Lleida, Catalonia: an assessment of contributory factors. J Nutr Elder. 2010;29:410-22. (PMID: 21104512)

18. Leandro-Merhi VA, de Aquino JL, Sales Chagas JF. Nutrition status and risk factors associated with length of hospital stay for surgical patients. JPEN J Parenter Enteral Nutr. 2011;35:241-8. (PMID: 20971940)

19. Robertson RG, Jameson JL. Chapter 80. Involuntary weight loss. In Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine, 18th edition. New York, NY: McGraw-Hill Professional

20. Rabinovitz M, Pitlik SD, Leifer M, Garty M, Rosenfeld JB. Unintentional weight loss. A retrospective analysis of 154 cases. Arch Intern Med. 1986;146:186-7. (PMID: 3942450)

21. Thompson MP, Morris LK. Unexplained weight loss in the ambulatory elderly. J Am Geriatr Soc. 1991;39:497-500. (PMID: 2022802)

22. Wallace JI, Schwartz RS. Involuntary weight loss in elderly outpatients: recognition, etiologies, and treatment. Clin Geriatr Med. 1997;13:717-35. (PMID: 9354751)

23. Verdery RB. Clinical evaluation of failure to thrive in older people. Clin Geriatr Med. 1997;13:769-78. (PMID: 9354754)

24. Sullivan DH, Martin W, Flaxman N, Hagen JE. Oral health problems and involuntary weight loss in a population of frail elderly. J Am Geriatr Soc. 1993;41:725-31. (PMID: 8315182)

http://www.ncbi.nlm.nih.gov/pubmed?term=22045479

























of 21

25. Ritchie CS, Joshipura K, Silliman RA, Miller B, Douglas CW. Oral health problems and significant weight loss among community-dwelling older adults. J Gerontol A Biol Sci Med Sci. 2000;55:M366-71. (PMID: 10898252)

26. Markson EW. Functional, social, and psychological disability as causes of loss of weight and independence in older community-living people. Clin Geriatr Med. 1997;13:639-52. (PMID: 9354746)

27. Ross C, Ancoli-Israel S, Redline S, Stone K, Fredman L. Association between insomnia symptoms and weight change in older women: caregiver--study of osteoporotic fractures study. J Am Geriatr Soc. 2011;59:1697-704. (PMID: 21883114)

28. Barrett-Connor E, Edelstein SL, Corey-Bloom J, Wiederholt WC. Weight loss precedes dementia in community-dwelling older adults. J Am Geriatr Soc. 1996;44:1147-52. (PMID: 8855991)

29. Sahyoun NR, Serdula MK, Galuska DA, Zhang XL, Pamuk ER. The epidemiology of recent involuntary weight loss in the United States population. J Nutr Health Aging. 2004;8:510-7. (PMID: 15543425)

30. Morley JE. Undernutrition: a major problem in nursing homes. J Am Med Dir Assoc. 2011;12:243-6. (PMID: 21527163)

31. Simmons SF, Keeler E, Zhuo X, Hickey KA, Sato HW, Schnelle JF. Prevention of unintentional weight loss in nursing home residents: a controlled trial of feeding assistance. J Am Geriatr Soc. 2008;56:1466-73. (PMID: 18637983)

32. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc. 1994;42:583-5. (PMID: 8201141)

33. Brymer C, Winograd CH. Fluoxetine in elderly patients: is there cause for concern? J Am Geriatr Soc. 1992;40:902-5. (PMID: 1512386)

34. Morley JE, Reese SS. Clinical implications of the aging heart. Am J Med. 1989;86:77-86. (PMID: 2642659)

35. Reife CM. Involuntary weight loss. Med Clin North Am. 1995;79:299-313. (PMID: 7877392)

36. Hernandez JL, Riancho JA, Matorras P, Gonzalez-Macias J. Clinical evaluation for cancer in patients with involuntary weight loss without specific symptoms. Am J Med. 2003;114:631-7. (PMID: 12798450)

37. Burke CW. Adrenocortical insufficiency. Clin Endocrinol Metab. 1985;14:947-76. (PMID: 3002680)

38. Lankisch P, Gerzmann M, Gerzmann JF, Lehnick D. Unintentional weight loss: diagnosis and prognosis. The first prospective follow-up study from a secondary referral centre. J Intern Med. 2001;249:41-6. (PMID: 11168783)

39. Mathey MF, Siebelink E, de Graaf C, Van Staveren WA. Flavor enhancement of food improves dietary intake and nutritional status of elderly nursing home residents. J Gerontol A Biol Sci Med Sci. 2001;56:M200-5. (PMID: 11283191)

40. Shevitz AH, Wilson IB, McDermott AY, Spiegelman D, Skinner SC, Antonsson K, et al. A comparison of the clinical and cost-effectiveness of 3 intervention strategies for AIDS wasting. J Acquir Immune Defic Syndr. 2005;38:399-406. (PMID: 15764956)

41. Agostini JV, Han L, Tinetti ME. The relationship between number of medications and weight loss or impaired balance in older adults. J Am Geriatr Soc. 2004;52:1719-23. (PMID: 15450051)

42. Milne AC, Avenell A, Potter J. Meta-analysis: protein and energy supplementation in older people. Ann Intern Med. 2006;144:37-48. (PMID: 16389253)

43. Lauque S, Arnaud-Battandier F, Mansourian R, Guigoz Y, Paintin M, Nourhashemi F, et al. Protein-energy oral supplementation in malnourished nursing-home residents. A controlled trial. Age Ageing. 2000;29:51-6. (PMID: 10690696)

44. Fiatarone Singh MA, Bernstein MA, Ryan AD, O’Neill EF, Clements KM, Evans WJ. The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders. J Nutr Health Aging. 2000;4:5-12. (PMID: 10828934)

45. Kayser-Jones J, Schell ES, Porter C, Barbaccia JC, Steinbach C, Bird WF, et al. A prospective study of the use of liquid oral dietary supplements in nursing homes. J Am Geriatr Soc. 1998;46:1378-86. (PMID: 9809759)

46. Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330:1769-75. (PMID: 8190152)

47. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia: a review of the evidence. JAMA. 1999;282:1365-70. (PMID: 10527184)

48. Oster MH, Enders SR, Samuels SJ, Cone LA, Hooton TM, Browder HP, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med. 1994;121:400-8. (PMID: 8053613) [Full Text]

49. Von Roenn JH, Armstrong D, Kotler DP, Cohn DL, Klimas NG, Tchekmedyian NS, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med. 1994;121:393-9. (PMID: 7794302) [Full Text]

50. Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M. Glucocorticoidlike activity of megestrol. A summary of Food

and Drug Administration experience and a review of the literature. Arch Intern Med. 1997;157:1651-6. (PMID: 9250225)

























http://www.annals.org/cgi/content/full/121/6/400


http://www.annals.org/cgi/content/full/121/6/393




of 21

51. Yeh SS, Wu SY, Lee TP, Olson JS, Stevens MR, Dixon T, et al. Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: results of a double-blind, placebo-

controlled study. J Am Geriatr Soc. 2000;48:485-92. (PMID: 10811540)

52. Lambert CP, Sullivan DH, Freeling SA, Lindquist DM, Evans WJ. Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial. J Clin Endocrinol Metab. 2002;87:2100-6. (PMID: 11994348)

53. Kardinal CG, Loprinzi CL, Schaid DJ, Hass AC, Dose AM, Athmann LM, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer. 1990;65:2657-62. (PMID: 2187585)

54. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12:913-9. (PMID: 9309469)

55. Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002;20:567-73. (PMID: 11786587)

56. Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, et al. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group. Ann Intern Med. 1996;125:873-82. (PMID: 8967667)

57. Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997;82:1661-7. (PMID: 9177359)

58. Yeh SS, DeGuzman B, Kramer T. Reversal of COPD-associated weight loss using the anabolic agent oxandrolone. Chest. 2002;122:421-8. (PMID: 12171812)

59. Hengge UR, Stocks K, Wiehler H, Faulkner S, Esser S, Lorenz C, et al. Double-blind, randomized, placebo-controlled phase III trial of oxymetholone for the treatment of HIV wasting. AIDS. 2003;17:699-710. (PMID: 12646793)

60. Kaplan G, Thomas S, Fierer DS, Mulligan K, Haslett PA, Fessel WJ, et al. Thalidomide for the treatment of AIDS-associated wasting. AIDS Res Hum Retroviruses. 2000;16:1345-55. (PMID: 11018854)

61. Gordon JN, Trebble TM, Ellis RD, Duncan HD, Johns T, Goggin PM. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005;54:540-5. (PMID: 15753541)

62. Jatoi A, Kumar S, Sloan JA, Nguyen PL. On appetite and its loss. J Clin Oncol. 2000;18:2930-2. (PMID: 10920143)

63. Fox CB, Treadway AK, Blaszczyk AT, Sleeper RB. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-97. (PMID: 19323618)

64. Huerta G, Viniegra L. Involuntary weight loss as a clinical problem. Rev Invest Clin. 1989;41:5-9. [Spanish] (PMID: 2727433)

















of 21

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



of 21

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.



of 21

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.



of 21

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.

involuntary weight loss · involuntary weight loss pier is copyrighted ©2013 by the american...

Documents