UNINTENDED WEIGHT LOSS

by
Glen E. Hastings MD
October 22, 2005

I The Clinical History is of unparalleled importance in the evaluation of a patient with documented
involuntary weight loss of 5% or more of body weight in one month or 10% over a 6 month period;
both of these occurrences have been shown to be strong predictors of 2 year mortality
1
. In one
series the appropriate diagnosis was made 92% of the time by careful medical history, physical
examination & screening laboratory tests alone
2
. It is therefore essential to take the time to perform
the appropriate evaluation because of the serious prognosis of this presenting problem & the almost
unlimited number of its potential causes. In a 1995 VA outpatient population a weight loss of 4% over
one year predicted subsequent mortality in 2 years with a sensitivity of 75% & specificity of 61%
3
.
The most frequent cause of involuntary weight loss in two recently reported cohorts of outpatients
2,,4

were depression & other psychiatric conditions (18%), cancer (17%), nonmalignant GI conditions
(13%), drug side effects (11%) & neurological disorders (11%). In 5% the problems were
environmental or socioeconomic & 25% remained unexplained. On the basis of these findings,
Gazewood & Mehr
5
recommended categorizing the causes of unintended weight loss as:
Conditions causing anorexia
Difficulty eating
Normal caloric intake with weight loss
Social or economic disruption
This categorization provides a rational organization for taking the medical history:
The first question to document is whether or not significant weight loss has in fact occurred.
Optimally, it is possible that the weight loss is documented in the medical record. Less precisely, the
patient or a caregiver may be able to estimate the weight loss on the basis of changes in clothing
size. Table 1 is a list of areas requiring exploration for patients with unexplained weight loss.
The patient should be asked directly about loss of appetite,
anorexia or nausea if those complaints arent volunteered
spontaneously.
Table 1: Symptom Modifiers
Duration?
Weight loss? Documentation?
A nutritional assessment should be performed which should
include a dietary log from which daily caloric intake may be
estimated. The Harris-Benedict equations can be used to
estimate daily caloric requirements (see the outline on Diabetes
Mellitus Type 2) for comparison.
Specific inquiry should be made about the possibility of
depressed mood. Especially the elderly are unlikely to
spontaneously volunteer that complaint. The Geriatric Depression Scale shown in the Appendix is an
excellent screening tool for covert depression in the elderly. Changes in the patients life that are
likely to be experienced as a loss should be elicited. For example: Asking for a home health aide to
work in the home, curtailment of driving privileges, or moving to live with relatives or to a nursing
home. A list of common causes for unintended weight loss are shown as Table 2 on the next page.
Daily caloric intake?
Associated Symptoms? Dysphagia?
Precipitating Factors:
(Especially depression or social disruption)
Abrupt or Gradual Onset?
Continuous or Intermittent?
Has It Happened Before?
Pattern of Prior Occurrences?
Symptoms of upper or lower dysphagia should be elicited by the history, a detailed neurological
examination should be performed to identify mechanical difficulties with eating, chewing or
swallowing. X-ray contrast swallowing studies should be obtained if the history is compatible with
esophageal dysphagia. The social history should document the extent of prior exposure to tobacco
smoke, asbestos particles, aromatic cleaning solvents & other environmental carcinogens. Family
history should be explored for evidence of a heritable cause. Symptoms from the GI tract should be
elicited & upper &/or lower endoscopic or x-ray dye contrast studies obtained if they are present. A
complete list of prescription & OTC drugs, vitamins & supplements should be evaluated for
appetite suppressing culprits. Table 3 is a list of prescription drugs known to be associated with
appetite suppression & the mechanisms of the side effect
6
.
Weight Loss: Page 2 of 6


II Anorexia is commonly caused by psychological disturbances, malignancies, GI diseases & adverse
reactions to prescribed drugs.
Covert depression is very common among the elderly, often evidenced by vegetative signs & rarely
by voiced complaint. Directly asking the patient if he or she feels depressed or has lost interest in
formerly enjoyed activities has a high sensitivity for identifying the depressed elderly. The Geriatric
Depression Scale shown in the Appendix is a more sensitive & specific tool for identifying depressed
older patients.
Psychological Bereavement is a very common cause of occult weight loss in the geriatric
population. Bereavement is obvious with the loss of a lifelong mate, but elderly patients frequently
experience bereavement after almost any lifestyle change necessitated by the exigencies of aging
(eg. change of residence, financial difficulties, loss of drivers license etc.).
Anorexia Tardive is anorexia nervosa when it occurs de novo
in the elderly. In one study 9% of anorexic elderly men with
unexplained weight loss were felt to have clinically significant
body image distortions as do younger anorexics
7
.
Table 2: Causes of Occult Weight Loss
Anorexia:
Psychiatric conditions:
Depression or Bereavement
Eating Disorders
Alcoholism
Cancer:
Lung, GI, Breast & Prostate
Nonmalignant GI Conditions:
Peptic Ulcer, GERD, Achalasia,
Diffuse Esophageal Spasm, GB or
Biliary Tract Disease
Renal Insufficiency
Cardiac Cachexia
HIV, TBC, SBE or Parasites.
Drugs (See Table 3)
Problem Eating:
Dental Decay & Missing Teeth
Movement Disorders (eg.Parkinsonism)
Stroke with paralysis
Neuromuscular Disorders (eg. ALS)
Dementia
Normal Caloric Intake:
Diabetes Mellitus
Hyperthyroidism
Celiac Sprue
Chronic Pancreatitis
Bacterial Overgrowth in the GI Tract
Social Disruption:
Social Isolation
Unpleasant Environmental Distractions
Poverty
Caretaker Burnout
Neglect or Abuse
Alcoholism is another poorly recognized cause of weight loss
among the elderly. The history of pathological alcohol intake is
unlikely to be mentioned unless the clinician makes a
thoroughly detailed nonjudgmental history of ethanol use.
Alzheimers Disease as well as other dementing illnesses not
infrequently present with paranoiac ideation &/or anosmia, both
of which are associated with anorexia & weight loss. As
dementia progresses, many of these patients literally forget to
eat & at the same time fail to notice the ensuing weight loss. As
neurological deterioration continues, patients with virtually all
types of dementia develop upper motor dysphagia & aspiration
risk. Terminally, many simply refuse to eat.
Lung & GI, & Breast Cancers are the malignancies most often
related to unintended weight loss so a careful history of tobacco
use & occupational or recreational exposure to known inhalant
carcinogens should, if positive be followed by chest CT.
Similarly, a careful GI history & physical examination should be
followed with upper &/or lower endoscopy, appropriate x-ray
contrast studies or CT or MRI of the abdomen as indicated.
Since GI motility problems are common nonmalignant causes of
unintended weight loss, a careful & complete GI workup will
identify many of these problems as well. Careful examination of
the breasts plus mammography are routine parts of the
diagnostic workup
Peptic Ulcer Disease, Gallbladder, Biliary Tract Disease & GERD are frequent causes of
anorexia. Usually these conditions are accompanied by other symptoms but these other symptoms
are often not perceived or reported by elderly patients. They should be considered & excluded.
Prescription Drugs
6
are one of the most common causes of anorexia & weight loss in the elderly.
Polypharmacy & failure to look for less obvious side effects like anorexia are underlying related
problems. Digoxin, amiodarone & theophyllin for example often cause anorexia while well within the
therapeutic range. Selective serotonin uptake inhibitors (SSRIs) & NSAIDs, either prescribed or
over-the-counter (OTC) are frequent culprits in elderly patients. Drugs with anticholinergic properties
either OTC or by prescription may cause xerostomia with consequent dysgeusia, dysphagia or
anorexia. See Table 3 on the next page for a list of drugs often related to weight loss & why.
Weight Loss: Page 3 of 6
Severe or Endstage Illnesses of many kinds, congestive heart failure, COPD, sepsis, giant cell
arteritis, hyperparathyroidism, hyper or hypothyroidism,
tuberculosis. Many acute & chronic illnesses release
interleukins & tumor necrosis factor promoting anorexia.
Table 3: Drugs Associated with Weight Loss
III Difficulty Eating is most often caused by dental,
neurological, neuromuscular & structural or motility
disorders of the GI tract are the most frequent reasons for
difficulty eating:
Dental & Oral Pathology were the most important
predictors of 12 month weight loss in older adults in a study
published in 1993
8
. Now perhaps we have an answer to
why the tooth-to tattoo ratio of <1 portends a poor
prognosis no matter what the primary diagnosis may be:
The answer is malnutrition!
Stroke, Multiple Sclerosis, Parkinsons Disease,
Amyotropic Lateral Sclerosis & Myesthenia Gravis may
make eating difficult in 2 ways: The primary dysfunctions of
bodily movement may make self feeding impossible. As
these conditions progress they often cause upper motor
(oropharyngeal) dysphagia, as may advanced Alzheimers
Disease & Polymyositis/Dermatomyositis. Once upper
motor dysphagia becomes established, a decision about long term tube feeding must be made. The
physicians role in this decision is not to decide but to educate the patient & family in the benefits &
expected complications, limitations & costs of long term tube feeding. Current evidence indicates that
long term tube feeding in patients with advanced dementia probably doesnt extend life, prevent
aspiration or engender weight gain.
Vision Loss is another barrier to food preparation & enjoyment
Esophogeal Spasm related to early achalasia or to diffuse esophageal spasm are clinically
indistinguishable. Both cause severe substernal chest pain which is in some cases severe enough to
produce Sitophobia, the fear of eating. As achalasia progresses, regurgitation of fetid undigested
food occurs if treatment is not given & at that point sitophobia is ubiquitous. Contrast x-ray imaging
studies & esophageal manometry are best for identifying most motility disorders
Esophageal Webs, Zenkers Diverticulae, Tumors & Thyroid Goiters are less common structural
causes of esophageal dysphagia. . Endoscopic visualization is required to identify the nature of
obstructive lesions.
May Cause Nausea or Vomiting:
-agonists, bisphosphonates, alopurinol,
amantadine, dopamine agonists &
carbodopa/levodopa, digoxin, macrolide
& tetracycline antibiotics, Iron supplements,
metronidazole, statins, metformin, NSAIDs,
nitroglycerine, opiates, phenyltoin, SSRIs,
potassium, xanthines
May Cause Dysphagia:
Bisphosphonates, macrolide & tetracycline
antibiotics, steroids, iron, NSAIDs & K
+
May Cause Dysguesia:
-agonists, alopurinol, ACE inhibitors,
antibiotics, anticholinergics, antihistamines
calcium channel blockers, dopamine
agonists & levodopa/carbadopa, statins,
metformin, metronidazole, nitroglycerine,
phenyltoin & tricyclic antidepressants.
May Cause Anorexia:
amantadine, antibiotics, antiepileptic drugs
benzodiazepines, decongestants, digoxin,
levodopa/carbodopa, metformin, opioids,
SSRIs & xanthines.
IV Weight Loss Despite Normal Caloric Intake may be caused by inability to absorb the ingested
calories, calorie loss, or any process that increases the bodys caloric requirements.
Diabetes Mellitus Type 2 may present with weight loss owing to loss of calories in the form of
glucose in the urine.
Hyperthyroidism & Pheochromocytoma regularly cause weight loss by increasing the baseline
metabolic rate.
Celiac Sprue, Pancreatic Exocrine Insufficiency & Bacterial Overgrowth within the lumen of the
bowel are the 3 leading causes of malabsorption of nutrients.
Celiac sprue occurs predominantly in older Caucasians of Northern European heritage. Small bowel
biopsy is required for definitive diagnosis of celiac disease but elevated serum levels of anti-gleiden &
anti-endomesial antibodies provide a presumptive diagnosis.
About 40% of patients with pancreatic exocrine insufficiency may be diagnosed by the
pathognomonic calcium stippling in the pancreatic bed on x-ray. The others may be identified using
spiral CT or MRI-CP. Either technique provides fine enough detail of the pancreatic duct to allow the
diagnosis of chronic pancreatitis to be made.
Before the advent of proton pump & H
2
inhibiting agents, peptic ulcer was predominantly a surgical
illness. Subtotal gastric resections & vagotomies were common treatments. The Billroth II
Weight Loss: Page 4 of 6
anastomosis, if improperly constructed would not completely empty into the small bowel. Bacterial
overgrowth occurred in the bowel loop, frequently resulting in malabsorption of food & other nutrient
substances. Older patients often still have such blind loops. Achlorhydria is another common
predisposition to bacterial overgrowth GI tract. Older patients with these conditions may or may not
have diarrhea.
V Social & Economic Problems are ubiquitous in the geriatric population & they color & shape what is
possible to do therapeutically as well as the outcome.
Poverty is endemic in the geriatric population. Why? A laborer who earned $400/month 30 years
ago was well paid, so it is only reasonable that he would have anticipated that a retirement income of
$400/month today would be more than adequate. How many of us could live on $400/month today?
Many elderly people try. Until they are bereft of all assets, including the old homestead is any
elderly Kansan eligible for any form of public assistance. The inability of most of our elders to eat
adequately is more often than not constrained be budgetary worries & fixed incomes the affluent few
that attend our offices notwithstanding. Inadequate income & inadequate insurance coverage are
among the most important determinants of patient non-compliance with medical recommendations.
Social Isolation is the nemesis of many elders. A life of work & coming home to the same wife for
60 years ends abruptly with her death & meals are no longer enjoyable. Later, after nursing home
placement, the loss of contact with a favorite nurse who moves to a new position may trigger the
same grief response in the old mans mind & body as did the loss of his wife.
Trivial Losses or even seemingly advantageous changes in the patients life may evoke outpourings
of the elderly patients primordial fears, anxieties & regrets during the end of life transition. Such
symbolically significant events must be identified & honored by the physician who is interested in
helping his patient cope with such changes. A part of the reaction to these changes usually includes
loss of appetite & weight loss.
Caregiver Burnout, Malice or Lack of Concern are major unrecognized situational causes of
weight loss among patients dependant upon others for completion of the normal activities of daily
living, both in the home & in institutional care settings.
Institutional Diets & Meals-on-Wheels are at best bland, & most prepared prescription diets are
virtually inedible. How can we expect an 80 year old woman with drug induced anorexia to maintain a
positive caloric intake with such food? Physicians need to make every effort to avoid prescription
diets in elderly patients with unexplained weight loss. Often, simply switching to an ad-lib diet fixes
the problem.
Environmental Disruption: In nursing homes it is scarcely possible to ignore the dining room sound
level at mealtimes. More cognitively intact patients often become so distracted or upset at the
behaviors of other more cognitively impaired patients in the dining room as to loose appetite.
Before attributing weight loss to social, economic or environmental factors however, it is incumbent
upon the physician to exclude other biological causes.
VI Laboratory Tests should be selectively targeted to the presenting complaint & other clinical clues
that arise from the history & physical examination. The diagnosis was correctly made in 92% of
cases in a series published 25 years ago. In that study the routinely obtained screening laboratory
work included a CMP, CBC with differential & platelets, TSH, urine analysis, fecal occult blood &
chest x-ray. Other tests such as x-ray contrast studies of the GI tract, upper & lower endoscopy were
selected if indicated by the history or physical findings. The highest yield tests were upper endoscopy
or upper GI x-ray contrast studies, TSH & fecal occult blood tests. All patients not found to have a
specific cause for unintended weight loss in that study were alive & doing well after 18 months of
followup
2
.
Current evidence therefore favors a parsimonious diagnostic workup based upon a careful &
complete medical history & physical examination, a screening battery of routine laboratory test similar
to those noted above, followed by other testing indicated by the history, exam & screening labs. If a
specific cause is not identified at that point, watchful waiting rather than shotgun testing is
recommended, because your patient may well be among the 25% for whom the etiology of the weight
loss remains obscure, the vast majority of whom recover without further incident.

Weight Loss: Page 5 of 6
VII Management:
The essential element of management is to address & hopefully to resolve the precipitating event or
condition. The problem of unintended weight loss however is more often than not multifactorial, so
the attending physician must evaluate the problem with broad vision, and avoid focusing prematurely
upon the first possible cause noticed.
Not infrequently part of the problem is iatrogenic. Older patients often accumulate an array of
prescription drugs prescribed years ago by more than one half remembered doctors for indications
that are now obscure. You or I sometimes refill this list almost as a reflex response to the patients
request. One or more drugs are probably unnecessary & that one could be the problem. Ask the
patient to put everything he takes for his health into a paper bag & bring it all to your office for you to
review. They dont always remember OTC drugs, prescriptions theyve taken for years or vitamins,
herbs & supplements. You need to see them all.
Ask yourself: Is it really necessary for 93yo Mrs. J ones to be on an ADA diet? Wouldnt it be better if
she would eat something, even if its not on the prescribed diet? Institutional food is rarely of gourmet
quality to begin with. When you add a dietary prescription it may become virtually inedible.
Unnecessary drugs & therapeutic diets might best be your first targets.
Occasionally but not often, nutritional supplements given between meals may help, as may offering
smaller, more frequent meals.
Employing an appetite stimulant is many times useful. No drugs are FDA approved for this indication
& there are no controlled trials, so the evidence of efficacy available is from published observational
studies, physiological reasoning & personal experience.
In my personal experience megestrol (Megace

) liquid in very low dosage (40mg or 1cc of the liquid

formulation, three times daily before meals) is affordable & almost always effective in elderly patients.
The hyperphagic effect continues after megestrol is discontinued. It is used for AIDS cachexia at
much higher dosage (at least 320mg/day), but at the higher dosages edema, constipation & mental
confusion become problematic.
Mirtazapine (Remeron

) promotes appetite & weight gain & can be a very effective agent in those
patients who are concomitantly suffering from depression.
Metoclopramide (Reglan

) is the most effective prokinetic bowel stimulator currently available in the

US. It sometimes helps nausea induced anorexia but it also may precipitate Parkinson-like dystonias
mental confusion & drug-drug interactions in the elderly.
Cyproheptadine (Periactin

) is an older antihistamine drug that, like metoclopamide, has

antiserotonin properties that stimulate peristalsis & mildly improve appetite. In my experience as well
as in the published literature, it seems a marginally effective agent for this purpose. It may also
cause drowsiness, dizziness & dry mouth or eyes.
Dronabinol (Marinol

) is a cannabinoid used to treat weight loss in AIDS patients. It isnt useful in

the elderly because it may cause confusion, dizziness & somnolence & it is expensive. Those in the
best position to know (e.g. users) continue to affirm that droabinol is inferior in efficacy to inhaled
cannabinoids. To my knowledge there is no high quality data about this issue.
Anabolic Steroids have been used in cancer & AIDS patients in conjunction with exercise to some
benefit. They have been shown to improve muscle mass & physical endurance in elderly men, but
the issue of weight gain has not been trialed to my knowledge.
VIII Prognosis:
The prognosis depends on the underlying cause of the weight loss. If a specific cause or causes
have not been found after the initial meticulous workup, the patient should be followed monthly in the
outpatient setting & the weight monitored because, if there is an organic cause that was not initially
identified, it usually becomes evident within 6 months
9,10
.
Weight Loss: Page 6 of 6

IX Bibliography:

1
Reife C M. Weight Loss. Ch. 36 in Harrisons Principles of Internal Medicine 16thEdition. Editors: Kasper DL, Fauci AS,
Longo DL, Braunwald E, Hauser SL, J ameson J L. McGraw-Hill NY,NY 2005 pages 233-5.

2
Marton KI, Sox HC J r, Krupp J R. Involuntary weight loss: diagnostic and prognostic significance. Ann Intern Med.
1981;95(5):568-74.

3
Wallace J I, Schwartz RS, LaCroix AZ, et al. Involuntary weight loss in older outpatients: incidence and clinical
significance. J Am Geriatr Soc. 1995;43(4):329-37.

4
Thompson MP, Morris LK. Unexplained weight loss in the ambulatory elderly. J Am Geriatr Soc. 1991;39(5):497-500.

5
Gazewood J D, Mehr DR. Diagnosis and management of weight loss in the elderly. J Fam Pract. 1998;47(1):19-25.

6
Huffman GB. Evaluating and treating unintentional weight loss in the elderly. Am Fam Physician. 2002;65(4):640-50.

7
Miller DK, Morley J E, Rubenstein LZ, Pietruszka FM. Abnormal eating attitudes and body image in older undernourished
individuals. J Am Geriatr Soc. 1991;39(5):462-6.

8
Sullivan DH, Martin W, Flaxman N, Hagen J E. Oral health problems and involuntary weight loss in a population of frail
elderly. J Am Geriatr Soc. 1993l;41(7):725-31.

9
Reife CM. Involuntary weight loss. Med Clin North Am. 1995;79(2):299-313.

10
Wallace J I, Schwartz RS. Involuntary weight loss in elderly outpatients: recognition, etiologies, and treatment. Clin Geriatr
Med. 1997;13(4):717-35.