Involuntary Weight Loss: Diagnostic and Prognostic Significance
KEITH I. MARTON, M.D.; HAROLD C. SOX, Jr., M.D.; and JAN R. KRUPP, M.D.; Palo Alto,
We prospectively evaluated 9 1 patients with involuntary
weight loss. Thirty-two ( 3 5 % ) had no identifiable physical
cause of weight loss, whereas the remainder had various
physical illnesses. During the year after the index visit, 23
( 2 5 % ) of the patients died and another 14 ( 1 5 % )
deteriorated clinically. Physical causes of weight loss
were clinically evident on the initial evaluation in 55 of 59
patients. The four patients in whom the diagnosis was
initially missed had cancer, and in only one of these
patients was the illness truly occult. Because diagnoses
were usually made rapidly in patients with a physical cause
of weight loss, we conclude that involuntary weight loss is
rarely due to "occult" disease. We developed a decision
rule that used six attributes to correctly identify 57 of 59
patients ( 9 7 % ) with a physical cause of weight loss and
23 of 32 patients without. Thus, our rule may help in the
early triage of patients with involuntary weight loss.
M A R K E D weight loss is generally viewed as a manifesta-
tion of serious disease ( 1 ) . The list of potential causes of
weight loss is extensive (1, 2), and the diseases causing
weight loss have many different pathophysiologic mecha-
nisms. The physician's diagnostic dilemma is further
complicated by at least three considerations. First, not all
patients with weight loss have serious physical illness, so
an extensive clinical evaluation will sometimes fail to
identify disease. Second, many patients who claim to
have lost weight have not lost weight at all ( 3 ) . Third,
there are no published studies of a cohort of patients with
weight loss and therefore no information on the relative
prevalence of various causes of weight loss. Thus, there is
From the Department of Medicine, Stanford University, and the Veterans Ad-
ministration Medical Center; Palo Alto, California.
Annals of Internal Medicine. 1 9 8 1 ; 9 5 : 5 6 8 - 5 7 4 .
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California
no firm basis for a comprehensive diagnostic approach to
patients with weight loss. Because of these difficulties, we
prospectively studied 91 patients with involuntary weight
loss to ascertain the common causes of weight loss, to
estimate the prognosis of patients with weight loss, and to
develop an efficient diagnostic strategy for such patients.
Methods
PATIENT SELECTION
Study patients were enrolled at the Palo Alto Veterans Medi-
cal Center between September 1975 and September 1978. Our
goal was to detect all patients whose weight loss was a diagnos-
tic problem to their physician. Therefore, all patients were be-
ing evaluated for weight loss when they were identified as possi-
ble study patients. Thirty patients (33%) had weight loss as the
chief complaint at the index visit. In the remainder, weight loss
was discovered as an incidental complaint because of docu-
mented changes in weight or because of the patient's physical
appearance. To find patients, we made weekly visits to the three
largest medical clinics and to the inpatient medical, surgical,
and psychiatric wards. The clinic staff were asked about pa-
tients with involuntary weight loss and were regularly reminded
to notify one of the investigators of any such patients. On the
inpatient wards, nurses and house staff were questioned about
patients with involuntary weight loss, and randomly chosen in-
patient charts were reviewed for any mention of involuntary
weight loss. To check on the adequacy of detection, the head
nurse in the general medical clinic reviewed the chart of every
patient seen during 3 months for evidence of weight loss, as
documented by serial measurements of body weight recorded at
each clinic visit. We also reviewed the charts of every patient
admitted to the medical service during a 3-month period
(March through May 1976) for evidence of recent weight loss
as recorded in the admitting history. On the basis of these data
we enrolled approximately 80% of all patients eligible for the
1 9 8 1 American College of Physicians
 study. Of the patients who were not enrolled, some had docu-
mented weight loss that was not being evaluated, whereas oth-
ers were being evaluated but had eluded our detection efforts.
Once a potential study patient was identified, his or her histo-
ry of weight loss was verified. Patients were eligible for the
study if they had lost at least 5% of their usual body weight
during the previous 6 months, as documented in their medical
record (59 patients). Patients who claimed weight loss, but
lacked this documentation, were eligible if they met at least two
of the following criteria: evidence of change in clothing size,
corroboration of the amount of weight loss by a friend or rela-
tive, and ability to give a numerical estimate of weight loss.
Such patients were felt to have a convincing history of weight
loss (32 patients). Approximately half the patients initially con-
sidered for enrollment had neither documented weight loss nor
a convincing history of weight loss.
Patients were excluded from the study for any of the follow-
ing reasons: The patient was actively trying to lose weight,
weight loss was associated with recent institution of diuretic
therapy, the patient already had a known cause of weight loss
(such as cancer), or the patient was unable to complete a health
questionnaire (usually because of severe psychiatric disease).
D A T A COLLECTION
After obtaining informed consent, we asked each patient to
fill out an 82-item questionnaire that included questions about
most of the known causes of weight loss and the previous medi-
cal history (see Appendix). One of the authors (K.M.) did a
physical examination and functional status assessment on each
patient. The remainder of the diagnostic evaluation was left to
the patient's physician. However, we requested that each pa-
tient have five screening tests: a complete blood count, a 12-
channel chemistry screening battery (SMA-12: includes aspar-
tate aminotransferase, alanine aminotransferase, lactic acid de-
hydrogenase, alkaline phosphatase, total and direct bilirubin,
cholesterol, uric acid, total protein, globulin, calcium, and inor-
ganic phosphate), a chest film, a urinalysis, and occult fecal
blood. The following proportions of the study population re-
ceived each test: blood count, 100%; SMA-12, 98%; chest film,
95%; and fecal blood, 77%.
We tried to re-evaluate each patient periodically for at least
12 months after enrollment. In some cases (see below) this was
not possible. Follow-up contact was made (in clinic or by tele-
phone) at 3, 6, and 12 months and the patient's weight and
functional status recorded each time. Functional status was
measured on a seven-point scale, ranging from dead [0] to fully
functional [ 6 ] . The mean length of follow-up was 77.5 weeks
(range, 26 to 141 weeks). Thirteen patients (14%) were seen
for less than a year but more than 6 months. All those patients
moved, and we were unable to contact them despite intensive
efforts. They were nonetheless included in the study because we
believed that we had adequate information to assign a firm diag-
nosis. The remainder were followed for at least 1 year. At the
end of the study, the following information was abstracted from
each patient's chart: tests obtained as part of the initial evalua-
tion, days spent in the hospital, and final diagnosis.
A S S I G N M E N T OF D I A G N O S I S
To assign a final diagnosis, two internists (K.M., H.S.) inde-
pendently reviewed each patient's entire chart at least 1 year
after enrollment. The two physicians used all available informa-
tion in the medical record but did not use the questionnaire
responses from the initial visit. A patient was considered to
have an identifiable cause of weight loss if the diagnostic evalua-
tion led to discovery of a disease known to cause weight loss
(such as cancer, malabsorption, thyrotoxicosis), if successful
treatment of a condition resulted in weight gain (for example,
depression), or if deterioration in disease status was paralleled
by further weight loss. The two physicians, who were unaware
of each other's diagnoses, agreed 87% of the time. Disagree-
ments were resolved by discussion of patient data.
DATA A N D DISCRIMINANT ANALYSES
Statistical comparisons were made by chi-squared with Fish-
er's correction and Student's f-test. We developed a decision
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Table 1 . Clinical Characteristics of Patients with Involuntary
Weight Loss
Characteristic
Age, mean ( i t S D ) , y r s 59.3 ( 17.5)
Follow-up, mean ( i t S D ) , wks 77.5 ( 30.2)
Maximum weight loss, mean (range), kg 11.6 (3.2-45.4)
Body weight loss ( S D ) , % 16 ( 7 )
Chief complaint, ( % ) *
Weight loss 33
Pain 30
Weakness 22
Pulmonary symptoms 22
Change in bowels 11
Neuropsychiatric complaint 9
Fevers/sweats/chills 9
Nausea/vomiting 8
Dysphagia 6
Other!
* Figures add up to more than 100, because many patients had several com-
plaints.
t Polyuria, polydipsia, polyphagia, anorexia, abnormal laboratory tests or phys-
ical finding.
rule whose purpose was to predict, with data from the initial
encounter, which patients would ultimately have a physical
cause for their weight loss and which patients would not. Thus,
the study population was divided into two groups: those with a
physical cause of weight loss and those without. By linear dis-
criminant analysis ( 4 ) , the two groups were then compared
with respect to the presence or absence of numerous clinical
attributes. Certain attributes were found to significantly and
independently discriminate between the two groups. The linear
discriminant function assigned a numerical value to each clini-
cal attribute that reflected its relative contribution to discrimi-
nating between the two groups.
In actual clinical practice, such a decision rule would be used
in the following way: After the patient's initial evaluation is
complete, a total linear discriminant score may be calculated by
ascertaining which of the important clinical attributes the pa-
tient has. If an attribute is present, it is given the score assigned
by the discriminant function. If the attribute is absent or un-
known, a score of 0 is assigned. The total score, known as the
patient's "weight loss score," assigns a patient to one of several
clinical groups that differ in the prevalence of patients with a
physical cause of weight loss.
Results
P A T I E N T CHARACTERISTICS
The study population consisted of 91 patients (90 men,
one woman). Seven additional patients were enrolled but
later dropped from the study for lack of any follow-up
information. At time of entry, 27 (30%) of the 91 pa-
tients were outpatients, and the remainder were inpa-
tients.
There were only two differences between the inpatients
and the outpatients. Outpatients were less likely to have
any physical findings suggestive of a physical cause of
weight loss (seven versus 44, p = 0.025) and were more
likely to have no physical cause of weight loss (13 versus
12, p = 0.05). Because there were so few differences be-
tween inpatients and outpatients and because 22 of the
outpatients were admitted to the hospital at least once
during the year of follow-up, we combined these two
groups for analysis.
We also compared the 59 patients who had document-
ed weight loss with the 32 who gave a convincing history
but had no previous weight recorded in the chart. The
Martonetal. Involuntary Weight Loss 5 6 9
 Table 2. Causes of Weight Loss in Study Patients
Diagnosis
N o physical cause found (n = 32)
N o apparent cause
Psychiatric
Physical cause found (n = 59)
Cancer
Gastrointestinal
Cardiovascular
Nutritional/alcoholic
Pulmonary
Endocrine/metabolic
Infectious
Granulomatous/inflammatory
Drug-induced
Neurologic
* Percentage figures add up to more than 100, because several patients had
more than one diagnosis. All percentages refer to the total 91 patients.
latter group of patients were new to our institution and
had not been evaluated by physicians outside our institu-
tion. There were no significant differences between these
two groups in their history, symptoms, diagnoses, or
status at follow-up.
The mean age of the patients was 59 years (Table 1),
and the mean weight loss was nearly 11.8 kg. One third
of the patients had weight loss as their chief complaint,
nearly one half had a chief complaint pointing to disease
of a specific organ (such as gastrointestinal or pulmonary
symptoms), and three fourths also had a nonspecific
chief complaint such as fever, weakness, anxiety, or an-
orexia (many patients had more than one chief com-
plaint). Patients with a chief complaint of weight loss
were quite similar to other patients in age, diagnoses,
outcome, and extent of diagnostic testing for weight loss,
but they were more likely to have entered the study
through the outpatient area (15 of 30 versus 12 of 61
[ 2 0 % ] , p = 0.04).
CAUSES OF W E I G H T LOSS
There were many causes of weight loss found among
the 91 study patients (Table 2). Cancer was the com-
monest physical cause of weight loss. Among the 18 pa-
tients with cancer were nine with lung cancer, three with
lymphoma, three with gastrointestinal cancer (one, eso-
phageal; one, gastric; and one, carcinoid), one with renal
cancer, one with cancer of prostate, and one with oral
cancer. The next most frequent physical cause of weight
loss was gastrointestinal disease, which included mal-
absorption, inflammatory bowel disease, severe esopha-
geal dysmotility, and diabetic enteropathy. A broad spec-
trum of conditions was associated with the weight loss in
the remainder of the patients. Nine percent
had severe cardiovascular disease (all had class III or
class IV congestive heart failure) with progressive weight
loss that was not diuretic induced. Eight percent were
malnourished as a result of alcohol abuse and gained
weight when hospitalized. Six percent had weight loss
associated with severe obstructive lung disease (that is,
hypoxemia and severe exercise limitation). Four percent
5 7 0 November 1981 Annals of Internal Medicine Volume 95 Number 5
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had endocrine or metabolic abnormalities, three with
Patients*
poorly controlled diabetes and one with thyrotoxicosis.
(72 = 91) The three patients with infections included two with pul-
monary tuberculosis and one with a lung abcess. One
n(%) patient had debilitating rheumatoid arthritis and one,
sarcoidosis. Two patients had weight loss secondary to
24 (26)
8 ( 9) medication-induced gastrointestinal symptoms; they re-
gained the weight when the offending medication was
18 (19) withdrawn. Two patients had such severe neurologic dis-
13(14) ease (one, Parkinson's disease; one, dysphagia after mul-
8 ( 9)
7 ( 8) tiple strokes) that they could not maintain adequate nu-
5 ( 6) tritional intake.
4 ( 4) A physical cause of weight loss was not identified in 32
3 ( 3) patients (35%). The absence of a physical cause of
2 ( 2) weight loss was often confirmed by extensive diagnostic
2 ( 2)
2 ( 2) evaluation (22 of these patients were hospitalized for
evaluation) and always confirmed by prolonged follow-
up. Twenty-nine of the 32 patients still lacked evidence of
a physical cause of weight loss 1 year after entry into the
study. The other three patients had no evidence for a
physical cause at 6 months follow-up but were lost to
follow-up thereafter. Twenty-three of these 32 patients
had coexisting chronic medical disease, such as hyperten-
sion, coronary artery disease, degenerative joint disease,
or cerebrovascular disease. However, these conditions
were present and clinically stable when the patient noted
weight loss and in no case were believed to be the cause
of weight loss. Eight patients had weight loss associated
with typical signs and symptoms of depression; these pa-
tients gained weight as their depression improved and
were therefore believed to have a definite psychiatric ba-
sis for weight loss. Another seven patients were believed
by some of the physicians caring for them to have a psy-
chiatric cause of weight loss, but there was no convincing
evidence that psychiatric illness was the cause of weight
loss. The remaining 17 patients clearly did not have a
physical illness causing weight loss, but the pathogenesis
of their problem was not identified.
OUTCOMES IN PATIENTS W I T H W E I G H T LOSS
The short-term prognosis in our patients with involun-
tary weight loss was poor. Twenty-three of the patients
(25%) died within a year of entry into the study, and 14
(15%) either continued to lose weight or deteriorate in
function. Thus, 36 of the study patients (40%) did poor-
Table 3. Outcomes in Patients with Involuntary Weight Loss
Outcome Physical Cause No Physical Cause
of Weight Loss of Weight Loss
(n = 59) (77 = 32)
Hospitalizations, mean
(SD),77 1.91 ( 1.51) 1.31 ( 1.14)
Duration of hospitaliza-
tion, mean ( SD), d 46.4 ( 57.3) 27.2 ( 47.5)
Deaths, 77(%)+ 21 (36) 2
Survivors with stable or
increased weight, 77 34/38 27/30
Survivors with stable or
increased function, 77 31/38 28/30
* P < 0.05.
 ly during the year of follow-up observations.
Outcome varied significantly, depending on whether
patients had a physical cause of weight loss (Table 3).
Thus, eight of the 32 patients without a physical cause
did poorly (two died, and six lost weight or had de-
creased function), whereas 48% of the 59 patients with a
physical cause did poorly (21 died, and eight lost weight
or had decrease in function). The difference in mortality
between the two groups is statistically significant (two
versus 21, p < 0.05). Two patients who did not have a
physical cause of weight loss died both suddenly and un-
expectedly, one of pneumonia and the other of a cerebro-
vascular accident. Autopsy failed to show a physical
cause of weight loss in either patient.
Patients who survived did well: Over 80% of the survi-
vors (55 patients) in the total group either maintained or
improved their functional status and weight during fol-
low-up.
When we compared the 36 persons who died or clini-
cally deteriorated with the 55 who remained stable or
improved during the study we found five attributes that
were significantly associated with outcome during the fol-
low-up period: age, diagnosis, initial functional status, re-
sults of initial screening tests, and weight during the year
before weight loss. Thus, 13 of the patients who did poor-
ly were over 80 years old compared to three of those who
did well (p < 0.005, chi-squared). Thirteen of the per-
sons who did poorly had cancer, whereas three of those
who did well had this diagnosis (p < 0.005, chi-
squared). Ten of the patients who did poorly needed as-
sistance walking when they entered the study. Only two
of the patients who did well were this disabled (p < 0.01,
chi-squared). Forty-one of the persons who did well had
completely normal findings of screening tests; none of the
patients who did poorly had normal findings on screening
tests (p < 0.001, chi-squared). Finally, nine of the per-
sons who did well had weighed more than 90.7 kg in the
year before their weight loss. None of the patients who
did poorly had weighed this much (p < 0.01, chi-
squared).
DIAGNOSTIC E V A L U A T I O N OF P A T I E N T S W I T H
W E I G H T LOSS
Study patients received a large amount of medical care.
Eighty-eight percent of the patients were hospitalized at
least once during the study (1.7 hospitalizations per pa-
tient, mean length of stay 39.6 days). Patients with a
physical cause of weight loss averaged 46.4 days
(SD 57.3, median = 30 days) in the hospital, whereas
patients without a physical cause averaged 27.2 days
(SD 47.5, median = 9 days) in the hospital.
Patients had numerous tests as part of their initial eval-
uation. Although all patients had weight loss, evaluation
was often directed at other problems as well (such as
pain, gastrointestinal symptoms, fever). We tried to re-
cord in the initial evaluation findings of those tests that
were directed at the patient's weight loss. Each patient
underwent an average of 14.5 tests (14.4 for patients
without a physical cause and 14.6 for patients with a
physical cause). We counted the SMA-12 as one test. In
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patients without a physical cause, the average number of
abnormal test results was only 1.5, whereas in patients
with a physical cause the average number of abnormal
results was three (p < 0.05, chi-squared). The average
charge (by Stanford Hospital charges) for this evaluation
would have been $364.40 for patients without a physical
cause and $389.93 for patients with a physical cause.
We also assessed the findings of selected laboratory
tests in the 59 patients with a physical cause of weight
loss. Chest radiology was the most useful examination,
showing a pertinent abnormality (such as mass, infiltrate,
heart failure, adenopathy) in 41% of these patients.
Chemistry tests showed an important abnormality 22%
of the time (primarily abnormal liver function test find-
ings). The blood count was abnormal in 14% (usually
anemia), and the urinalysis was abnormal in 3%. All
urinalyses with abnormal findings showed evidence of di-
abetes and thus duplicated the results of the blood sugar
measurement. Sixty-six percent of these patients had at
least one abnormal screening test (sensitivity = 0.66).
Of the tests done besides screening tests, the upper gas-
trointestinal series radiograph had the highest yield.
Twenty percent (12 patients) of the patients with a phys-
ical illness had an abnormal gastrointestinal series radio-
graph (usually evidence of ulcer disease or esophageal
disease). All the patients with an abnormal gastrointesti-
nal series radiograph had symptoms suggestive of gastro-
intestinal disease. Altogether, 49 of the 59 patients
(83%) with a physical cause of weight loss had abnormal
findings on screening test or abnormalities on gastrointes-
tinal series radiograph. Twenty of the 32 patients without
a physical cause of weight loss, however, had all normal
findings on screening tests (false-positive rate = 0.37).
In nearly every case, physical causes of weight loss
were readily apparent to the physicians caring for the
patients. Thus, the mean duration from the beginning of
the evaluation to the diagnosis of a physical cause of
weight loss was 15.1 days (range, 1 to 183 days, median 6
days). Longer than 30 days was needed for diagnosis in
six patients (10%). Two patients (one with a gastric ul-
cer, the other with carcinoid) were observed for a period
(40 and 52 days) before a decision was made to do the
definitive diagnostic test (gastrointestinal series radio-
graph and colonoscopy). Three patients (all with lung
cancer) had their diagnosis delayed (51, 80, and 183
days) because abnormalities on the initial chest films
were not noted and acted on. Retrospective analysis of
the chest films after the diagnosis had been made in these
patients showed clear-cut abnormalities. All died within
7 months of their presentation with weight loss. One pa-
tient with lung cancer may be considered to have had a
truly occult malignancy. He had received a thorough
evaluation during his first hospitalization for weakness
and weight loss and been discharged with a diagnosis of
depression. He was readmitted 4 months later with fur-
ther weight loss and back pain. A new lytic lesion in his
spine was found to be adenocarcinoma. When he died 3
weeks later the primary cancer of the lung was identified
at autopsy. It never had been noted on any chest film. In
patients without a physical cause of weight loss a mean
Marion eta/. Involuntary Weight Loss 571
 Table 4. Linear Discriminant Function for Weight Loss
Attribute
Less than 20 pack-years of smoking
No decrease in activities due to fatigue
Patient complaints of nausea/vomiting
Recent improvement in appetite
Cough that has recently changed
Findings of physical examination suggesting physical
cause of weight loss
Correction factor
Total
* The attribute scores were rounded off for ease in using the rule. However, the
accuracy of the rule was not affected by rounding off.
duration of 29 days (median, 10 days; range, 1 to 180
days) was needed before the evaluation was considered
complete.
A DIAGNOSTIC STRATEGY FOR WEIGHT LOSS
One goal of this study was to develop an initial diag-
nostic strategy that would quickly distinguish patients
with a physical cause of weight loss from patients with no
physical cause of weight loss. Multivariate discriminant
analysis of all 91 patients showed six attributes (of 123
tested) that were significant, independent diagnostic pre-
dictors (Tables 4 and 5). All six attributes were findings
of history and physical examination; findings of screening
laboratory tests were weaker predictors. Patients who
had maintained the same level of activity during weight
loss and who smoked relatively little were unlikely to
have a physical cause of weight loss. Patients who had
nausea or vomiting, a recent increase in appetite, or a
cough that had recently changed (in frequency, produc-
tivity, or severity) were likely to have a physical cause of
weight loss. Patients in whom findings of physical exami-
nation suggested a physical cause of weight loss (such as
cachexia, abdominal mass, adenopathy, thyromegaly)
were also more likely to have a physical cause. A pa-
tient's discriminant score (weight loss score), was calcu-
lated by summing the coefficients of all findings that were
present. The higher the score, the less likely the patient
was to have a physical cause of weight loss. Thus, all 26
patients with a score of 6 or less had a physical cause of
weight loss, 31 of the 40 patients with a score of 7 to 8
had a physical cause, two of the 14 patients with a score
of 9 to 11 had a physical cause, and none of the 11 pa-
tients with a score of 12 or greater had a physical cause of
weight loss. With a score of less than 9 used to indicate a
physical cause of weight loss, the sensitivity of the rule is
0.97 and the false-positive rate 0.28. The two patients
who had a physical cause of weight loss and a score of 9
or greater had obvious diseases: One had alcoholic liver
disease, and the other had severe diarrhea due to diabetic
enteropathy.
The discriminant rule was developed on all the study
patients. Because the discriminant calculation creates a
rule that is optimum for the population on which it is
developed, testing such a rule to assess its reliability is
important. Because of the practical problems of prospec-
tively testing a rule in a second group of weight loss pa-
tients, we used a statistical techniqueknown as the
572 November 1981 Annals of Internal Medicine Volume 95 Number 5
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leaving-one-out method (5, 6)to test our rule. This
method involves recomputing the discriminant rule a se-
Score* ries of times, each time with one patient left out of the
+3 calculation. The rule is then applied to that patient, and
+5 whether the patient has been correctly classified is deter-
3 mined. The number of misclassifications is a reasonably
2 unbiased indication of how well the rule will work in
1
other settings. When this method was applied to our pop-
1 ulation, the rule had an error rate of 12%. Most misclas-
+8 sifications involved patients without a physical cause of
1-16 weight loss. Specifically, the rule misclassified nine of 32
patients without a physical cause of weight loss and 2 of
59 patients (3%) with a physical cause: exactly the same
as during the initial calculations. Hence, the error rate of
this particular rule appears to be fairly stable.
Discussion
Involuntary weight loss is a common complaint. In our
medical clinic we found that nearly 8% of 1200 consecu-
tive patients claimed that they had lost over 2.3 kg during
the previous 6 months without trying (we did not ascer-
tain how many actually had documented weight loss).
Certainly, weight loss is a matter of concern to most phy-
sicians. Our study supports several commonly accepted
beliefs concerning weight loss and refutes at least one.
First, we found that many persons who claimed signifi-
cant weight loss had not actually lost weight. Almost half
the persons considered for the study did not have weight
loss, as documented by recorded stable weights. There
was a group of patients, however, in whom weight loss
could not be confirmed or refuted by available data.
These patients were clinically indistinguishable from pa-
tients with documented weight loss. All had a convincing
history of weight loss (for example, change in clothing
size, confirmation of history by a family member, or abili-
ty to give exact weight change). We conclude, therefore,
that the physician should seek, but not necessarily re-
quire, actual documentation of weight loss before pro-
ceeding with further evaluation. A convincing history of
weight loss may sometimes be sufficient.
Second, weight loss is a potentially serious symptom:
Twenty-five percent of the patients died within a year of
entry into the study, and another 15% continued to lose
weight or deteriorate in function. Most patients who did
poorly had cancer or cardiopulmonary disease. In other
settings with younger patients or fewer patients with can-
cer, however, the prognostic implication of weight loss
may not be so grim.
On the other hand, not all patients with weight loss
Table 5. Performance of the Linear Discriminant Rule
Rule Patients Patients Patients in
Score With With N o Score Group
Physical Physical With a
Cause Cause Physical Cause
n %
1-6 26 0 100
7-8 31 9 78
9-11 2 12 14
12-16 0 11 0
 have a serious physical illness, given our finding of a 35%
prevalence of no physical cause of weight loss. Of course,
such a conclusion depends on the validity of our diagnos-
es. Whereas the diagnostic end point for physical causes
of weight loss was clear, diagnoses in patients without a
physical cause of weight loss were usually made by the
exclusion of disease. Considering the long follow-up on
these patients, we believe that this strategy was adequate
for ruling out disease. Moreover, physical causes of
weight loss were always apparent within 6 months of the
initial evaluation, even in those few patients in whom the
diagnosis was first missed. Hence, we believe that 6
months of follow-up is generally adequate for excluding
physical causes of weight loss.
Our findings also show the difficulty in understanding
the pathogenesis of weight loss. Study patients with no
discernible physical cause of weight loss could have lost
weight because of decreased caloric intake, a change in
metabolism, or loss of calories. We did not attempt pre-
cise estimates of caloric intake, basal metabolism, or ca-
loric loss; such measurements should be done in future
studies of involuntary weight loss. We also occasionally
found it difficult to be sure of a cause-and-effect relation
between weight loss and physical illness. Although the
relation between cancer and weight loss is well known
( 7 ) , there may be multiple mechanisms of weight loss in
chronic obstructive lung disease or cardiovascular disease
(8-10). We often attributed weight loss to disease when
changes in disease status paralleled weight gain or weight
loss. Although we could not always be sure of the
strength of the relation between diagnosed disease and
observed weight loss, the high level of agreement between
two independent diagnosticians indicates that our causal
inferences would be accepted by most physicians.
The commonly held belief in "occult" malignancy as a
cause of weight loss was not supported by our findings.
By occult, we mean not apparent after the initial evalua-
tion. The belief in occult disease may lead to intensifica-
tion of the diagnostic evaluation of patients in whom ini-
tial studies are unrevealing. This phenomenon occurred
in our patients without a physical cause of weight loss,
who had the same number of tests as those with a physi-
cal cause, albeit with fewer abnormal results. We ob-
served, however, that a physical cause of weight loss was
almost always apparent after a brief evaluation. Although
extensive investigation was sometimes needed to eluci-
date the exact diagnosis or extent of serious disease, it
was almost never needed to ascertain whether serious dis-
ease was actually present. In almost every patient with
organic abnormalities, the initial history and findings of
physical and laboratory examination (blood count, chest
roentgenogram, SMA-12, urinalysis, and stool for occult
blood) accurately guided the physicians in deciding
whether to do tests that proved the diagnosis (for exam-
ple, gastrointestinal radiography, sputum cytologic stud-
ies).
The diagnosis was elusive in only four of 59 patients
with physical causes. All four had lung cancer. Two had
obvious chest roentgenographic findings of cancer that
were initially attributed to other causes (pneumonia, old
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tuberculosis). A third had a normal chest roentgeno-
gram. Each of these three patients needed a second hospi-
talization before the correct diagnosis was made. The di-
agnosis in a fourth patient, who also had lung cancer, was
not made until 51 days after his initial presentation. Al-
though his initial chest roentgenogram was misinterpret-
ed as normal (in retrospect, it showed a hilar mass), his
symptoms and other laboratory test results convinced his
physicians that he had a serious illness. After hospitaliza-
tion, a vocal cord paralysis developed, leading to the cor-
rect diagnosis. Thus, weight loss was a late symptom in
patients with serious disease. By the time weight loss was
present, either other specific disease manifestations were
readily apparent or the disease was too advanced for ef-
fective treatment. We therefore believe that when the ini-
tial evaluation of weight loss is unrevealing, a period of
watchful waiting is generally preferable to an exhaustive
search for occult malignancy.
We found that multivariate analysis enhanced the di-
agnostic value of easily obtained clinical data. Most stud-
ies that have correlated clinical information with diagno-
sis have reported the predictive value of single clinical
attributes. Because clinicians often use combinations of
attributes to make a diagnosis, multivariate analysis,
which defines the most effective attributes and the opti-
mum relative weighting, should provide a more realistic
model for interpreting clinical data. This approach has
been successfully used by Goldman and colleagues (11)
in their study of cardiovascular risk factors in surgical
patients and in our study (12) of the clinical usefulness
of the upper gastrointestinal series radiograph. In both
these studies and the present one, a group at very low risk
of a serious outcome could be defined by easily acquired
data. Because the decision rule requires only a history
and physical examination, it might have resulted in a no-
ticeable decrease in diagnostic tests for those of our pa-
tients whose weight loss score placed them in a low-risk
group.
Because patients without other specific complaints and
a high weight loss score (9 or more) are very likely to be
free of serious disease, the physician may choose to reas-
sure them and observe their clinical course. Further eval-
uation should center on possible psychiatric problems or
inadequate caloric intake rather than diagnostic tests for
serious, but clinically inapparent, disease. Patients with a
low score (8 or less), however, should be evaluated fur-
ther because the probability of a physical cause of weight
loss is very high. In such patients, history and findings of
physical examination and the initial laboratory evalua-
tion (consisting of a blood count, chest film, SMA-12,
stool for occult blood, and urinalysis) will usually sug-
gest the diagnosis. The principal concern in using the
weight loss rule is its applicability to other populations.
Until experience in other settings has accumulated, the
weight loss rule should be used as but one piece of evi-
dence among many in deciding the direction of a pa-
tient's evaluation. Thus, many clinicians may still wish to
do screening laboratory tests in all patients with weight
loss rather than only in those with a screening score of 8
or less.
Martonetal. Involuntary Weight Loss 5 7 3
 Involuntary weight loss is a nonspecific symptom. Like
fever and weakness, it may be either a manifestation of a
life-threatening illness or a symptom without a disease.
The cause of weight loss in contrast to that of fever and
weakness, however, will almost always be readily appar-
ent to clinicians who use history, physical examination,
and laboratory tests in a careful, discerning manner.
Appendix: the Weight Loss Questionnaire
We developed an 80-item questionnaire designed to obtain
information about most of the commonly known causes of
weight loss. Briefly summarized, it included questions about the
following:
1. Past history: previous weight, alcohol intake, smoking his-
tory, drug use, previous surgery, previous tuberculosis, other
previous illness.
2. Social history: occupational history, pets, marital history,
living arrangements, education, travel history, loss of spouse or
close relative, dentures, income, number of meals, recent diet-
ing.
3. Nonspecific symptoms: taste, smell, fever, hypothermia,
chills, sweats, fatigue, appetite, libido, sexual activity.
4. Specific symptoms: bowel habits (size, shape, color, fre-
quency), abdominal pain (frequency, characteristics), jaundice,
vomiting, dysphagia, hematuria, edema, urinary symptoms,
shortness of breath, cough, chest pain, voice changes, muscle
weakness, neurologic symptoms (tingling, forgetfulness, head-
aches), psychiatric symptoms (depression, anxiety, hypochon-
driasis), temperature, intolerance, musculoskeletal pain, bruis-
ing.
5. Functional status: work capacity, ambulation (aids, dis-
tance).
ACKNOWLEDGMENTS: The authors thank Linda Wells for her help in
574 November 1981 Annals of Internal Medicine Volume 95 Number 5
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preparing the manuscript, Carol Sox for programming the data analysis, and
Lynne Marton for assisting in the data entry.
Grant support: The Robert Wood Johnson Clinical Scholars Program and
the Veterans Administration.
This paper was presented at the Thirty-Seventh Annual National Meeting
of the American Federation for Clinical Research, 10-12 May 1980, in
Washington, D.C.
Requests for reprints should be addressed to Keith I. Marton, M.D.; Palo
Alto Veterans Administration Medical Center, 3801 Miranda Avenue; Palo
Alto, CA 94304.
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