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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, California

We prospectively evaluated 9 1 patients with involuntary no firm basis for a comprehensive diagnostic approach to
weight loss. Thirty-two ( 3 5 % ) had no identifiable physical patients with weight loss. Because of these difficulties, we
cause of weight loss, whereas the remainder had various prospectively studied 91 patients with involuntary weight
physical illnesses. During the year after the index visit, 23
( 2 5 % ) of the patients died and another 14 ( 1 5 % ) loss to ascertain the common causes of weight loss, to
deteriorated clinically. Physical causes of weight loss estimate the prognosis of patients with weight loss, and to
were clinically evident on the initial evaluation in 55 of 59 develop an efficient diagnostic strategy for such patients.
patients. The four patients in whom the diagnosis was
initially missed had cancer, and in only one of these Methods
patients was the illness truly occult. Because diagnoses
PATIENT SELECTION
were usually made rapidly in patients with a physical cause
of weight loss, we conclude that involuntary weight loss is Study patients were enrolled at the Palo Alto Veterans Medi-
rarely due to "occult" disease. We developed a decision cal Center between September 1975 and September 1978. Our
rule that used six attributes to correctly identify 57 of 59 goal was to detect all patients whose weight loss was a diagnos-
patients ( 9 7 % ) with a physical cause of weight loss and tic problem to their physician. Therefore, all patients were be-
23 of 32 patients without. Thus, our rule may help in the ing evaluated for weight loss when they were identified as possi-
early triage of patients with involuntary weight loss. 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-
M A R K E D weight loss is generally viewed as a manifesta- mented changes in weight or because of the patient's physical
tion of serious disease ( 1 ) . The list of potential causes of appearance. To find patients, we made weekly visits to the three
weight loss is extensive (1, 2), and the diseases causing largest medical clinics and to the inpatient medical, surgical,
and psychiatric wards. The clinic staff were asked about pa-
weight loss have many different pathophysiologic mecha- tients with involuntary weight loss and were regularly reminded
nisms. The physician's diagnostic dilemma is further to notify one of the investigators of any such patients. On the
complicated by at least three considerations. First, not all inpatient wards, nurses and house staff were questioned about
patients with weight loss have serious physical illness, so patients with involuntary weight loss, and randomly chosen in-
patient charts were reviewed for any mention of involuntary
an extensive clinical evaluation will sometimes fail to weight loss. To check on the adequacy of detection, the head
identify disease. Second, many patients who claim to nurse in the general medical clinic reviewed the chart of every
have lost weight have not lost weight at all ( 3 ) . Third, patient seen during 3 months for evidence of weight loss, as
there are no published studies of a cohort of patients with documented by serial measurements of body weight recorded at
each clinic visit. We also reviewed the charts of every patient
weight loss and therefore no information on the relative admitted to the medical service during a 3-month period
prevalence of various causes of weight loss. Thus, there is (March through May 1976) for evidence of recent weight loss
as recorded in the admitting history. On the basis of these data
From the Department of Medicine, Stanford University, and the Veterans Ad-
ministration Medical Center; Palo Alto, California. we enrolled approximately 80% of all patients eligible for the
Annals of Internal Medicine. 1 9 8 1 ; 9 5 : 5 6 8 - 5 7 4 . 1 9 8 1 American College of Physicians

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study. Of the patients who were not enrolled, some had docu- Table 1 . Clinical Characteristics of Patients with Involuntary
mented weight loss that was not being evaluated, whereas oth- Weight Loss
ers were being evaluated but had eluded our detection efforts.
Once a potential study patient was identified, his or her histo- Characteristic
ry of weight loss was verified. Patients were eligible for the
study if they had lost at least 5% of their usual body weight Age, mean ( i t S D ) , y r s 59.3 ( 17.5)
during the previous 6 months, as documented in their medical Follow-up, mean ( i t S D ) , wks 77.5 ( 30.2)
record (59 patients). Patients who claimed weight loss, but Maximum weight loss, mean (range), kg 11.6 (3.2-45.4)
lacked this documentation, were eligible if they met at least two Body weight loss ( S D ) , % 16 ( 7 )
of the following criteria: evidence of change in clothing size, Chief complaint, ( % ) *
corroboration of the amount of weight loss by a friend or rela- Weight loss 33
tive, and ability to give a numerical estimate of weight loss. Pain 30
Such patients were felt to have a convincing history of weight Weakness 22
loss (32 patients). Approximately half the patients initially con- Pulmonary symptoms 22
sidered for enrollment had neither documented weight loss nor Change in bowels 11
a convincing history of weight loss. Neuropsychiatric complaint 9
Patients were excluded from the study for any of the follow- Fevers/sweats/chills 9
ing reasons: The patient was actively trying to lose weight, Nausea/vomiting 8
weight loss was associated with recent institution of diuretic Dysphagia 6
therapy, the patient already had a known cause of weight loss Other!
(such as cancer), or the patient was unable to complete a health
questionnaire (usually because of severe psychiatric disease). * Figures add up to more than 100, because many patients had several com-
plaints.
D A T A COLLECTION t Polyuria, polydipsia, polyphagia, anorexia, abnormal laboratory tests or phys-
After obtaining informed consent, we asked each patient to ical finding.
fill out an 82-item questionnaire that included questions about rule whose purpose was to predict, with data from the initial
most of the known causes of weight loss and the previous medi- encounter, which patients would ultimately have a physical
cal history (see Appendix). One of the authors (K.M.) did a cause for their weight loss and which patients would not. Thus,
physical examination and functional status assessment on each the study population was divided into two groups: those with a
patient. The remainder of the diagnostic evaluation was left to physical cause of weight loss and those without. By linear dis-
the patient's physician. However, we requested that each pa- criminant analysis ( 4 ) , the two groups were then compared
tient have five screening tests: a complete blood count, a 12- with respect to the presence or absence of numerous clinical
channel chemistry screening battery (SMA-12: includes aspar- attributes. Certain attributes were found to significantly and
tate aminotransferase, alanine aminotransferase, lactic acid de- independently discriminate between the two groups. The linear
hydrogenase, alkaline phosphatase, total and direct bilirubin, discriminant function assigned a numerical value to each clini-
cholesterol, uric acid, total protein, globulin, calcium, and inor- cal attribute that reflected its relative contribution to discrimi-
ganic phosphate), a chest film, a urinalysis, and occult fecal nating between the two groups.
blood. The following proportions of the study population re- In actual clinical practice, such a decision rule would be used
ceived each test: blood count, 100%; SMA-12, 98%; chest film, in the following way: After the patient's initial evaluation is
95%; and fecal blood, 77%. complete, a total linear discriminant score may be calculated by
We tried to re-evaluate each patient periodically for at least ascertaining which of the important clinical attributes the pa-
12 months after enrollment. In some cases (see below) this was tient has. If an attribute is present, it is given the score assigned
not possible. Follow-up contact was made (in clinic or by tele- by the discriminant function. If the attribute is absent or un-
phone) at 3, 6, and 12 months and the patient's weight and known, a score of 0 is assigned. The total score, known as the
functional status recorded each time. Functional status was patient's "weight loss score," assigns a patient to one of several
measured on a seven-point scale, ranging from dead [0] to fully clinical groups that differ in the prevalence of patients with a
functional [ 6 ] . The mean length of follow-up was 77.5 weeks physical cause of weight loss.
(range, 26 to 141 weeks). Thirteen patients (14%) were seen
for less than a year but more than 6 months. All those patients Results
moved, and we were unable to contact them despite intensive
efforts. They were nonetheless included in the study because we P A T I E N T CHARACTERISTICS
believed that we had adequate information to assign a firm diag- The study population consisted of 91 patients (90 men,
nosis. The remainder were followed for at least 1 year. At the one woman). Seven additional patients were enrolled but
end of the study, the following information was abstracted from
each patient's chart: tests obtained as part of the initial evalua-
later dropped from the study for lack of any follow-up
tion, days spent in the hospital, and final diagnosis. information. At time of entry, 27 (30%) of the 91 pa-
A S S I G N M E N T OF D I A G N O S I S tients were outpatients, and the remainder were inpa-
To assign a final diagnosis, two internists (K.M., H.S.) inde- tients.
pendently reviewed each patient's entire chart at least 1 year There were only two differences between the inpatients
after enrollment. The two physicians used all available informa- and the outpatients. Outpatients were less likely to have
tion in the medical record but did not use the questionnaire any physical findings suggestive of a physical cause of
responses from the initial visit. A patient was considered to
have an identifiable cause of weight loss if the diagnostic evalua- weight loss (seven versus 44, p = 0.025) and were more
tion led to discovery of a disease known to cause weight loss likely to have no physical cause of weight loss (13 versus
(such as cancer, malabsorption, thyrotoxicosis), if successful 12, p = 0.05). Because there were so few differences be-
treatment of a condition resulted in weight gain (for example, tween inpatients and outpatients and because 22 of the
depression), or if deterioration in disease status was paralleled
outpatients were admitted to the hospital at least once
by further weight loss. The two physicians, who were unaware
of each other's diagnoses, agreed 87% of the time. Disagree- during the year of follow-up, we combined these two
ments were resolved by discussion of patient data. groups for analysis.
DATA A N D DISCRIMINANT ANALYSES We also compared the 59 patients who had document-
Statistical comparisons were made by chi-squared with Fish- ed weight loss with the 32 who gave a convincing history
er's correction and Student's f-test. We developed a decision but had no previous weight recorded in the chart. The
Martonetal. Involuntary Weight Loss 5 6 9

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Table 2. Causes of Weight Loss in Study Patients had endocrine or metabolic abnormalities, three with
Diagnosis 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,
N o physical cause found (n = 32)
sarcoidosis. Two patients had weight loss secondary to
N o apparent cause 24 (26)
Psychiatric 8 ( 9) medication-induced gastrointestinal symptoms; they re-
Physical cause found (n = 59) gained the weight when the offending medication was
Cancer 18 (19) withdrawn. Two patients had such severe neurologic dis-
Gastrointestinal 13(14) ease (one, Parkinson's disease; one, dysphagia after mul-
Cardiovascular 8 ( 9)
Nutritional/alcoholic 7 ( 8) tiple strokes) that they could not maintain adequate nu-
Pulmonary 5 ( 6) tritional intake.
Endocrine/metabolic 4 ( 4) A physical cause of weight loss was not identified in 32
Infectious 3 ( 3) patients (35%). The absence of a physical cause of
Granulomatous/inflammatory 2 ( 2) weight loss was often confirmed by extensive diagnostic
Drug-induced 2 ( 2)
Neurologic 2 ( 2) evaluation (22 of these patients were hospitalized for
evaluation) and always confirmed by prolonged follow-
* Percentage figures add up to more than 100, because several patients had
more than one diagnosis. All percentages refer to the total 91 patients.
up. Twenty-nine of the 32 patients still lacked evidence of
a physical cause of weight loss 1 year after entry into the
latter group of patients were new to our institution and study. The other three patients had no evidence for a
had not been evaluated by physicians outside our institu- physical cause at 6 months follow-up but were lost to
tion. There were no significant differences between these follow-up thereafter. Twenty-three of these 32 patients
two groups in their history, symptoms, diagnoses, or had coexisting chronic medical disease, such as hyperten-
status at follow-up. sion, coronary artery disease, degenerative joint disease,
The mean age of the patients was 59 years (Table 1), or cerebrovascular disease. However, these conditions
and the mean weight loss was nearly 11.8 kg. One third were present and clinically stable when the patient noted
of the patients had weight loss as their chief complaint, weight loss and in no case were believed to be the cause
nearly one half had a chief complaint pointing to disease of weight loss. Eight patients had weight loss associated
of a specific organ (such as gastrointestinal or pulmonary with typical signs and symptoms of depression; these pa-
symptoms), and three fourths also had a nonspecific tients gained weight as their depression improved and
chief complaint such as fever, weakness, anxiety, or an- were therefore believed to have a definite psychiatric ba-
orexia (many patients had more than one chief com- sis for weight loss. Another seven patients were believed
plaint). Patients with a chief complaint of weight loss by some of the physicians caring for them to have a psy-
were quite similar to other patients in age, diagnoses, chiatric cause of weight loss, but there was no convincing
outcome, and extent of diagnostic testing for weight loss, evidence that psychiatric illness was the cause of weight
but they were more likely to have entered the study loss. The remaining 17 patients clearly did not have a
through the outpatient area (15 of 30 versus 12 of 61 physical illness causing weight loss, but the pathogenesis
[ 2 0 % ] , p = 0.04). of their problem was not identified.

CAUSES OF W E I G H T LOSS OUTCOMES IN PATIENTS W I T H W E I G H T LOSS


There were many causes of weight loss found among The short-term prognosis in our patients with involun-
the 91 study patients (Table 2). Cancer was the com- tary weight loss was poor. Twenty-three of the patients
monest physical cause of weight loss. Among the 18 pa-
(25%) died within a year of entry into the study, and 14
tients with cancer were nine with lung cancer, three with
lymphoma, three with gastrointestinal cancer (one, eso- (15%) either continued to lose weight or deteriorate in
phageal; one, gastric; and one, carcinoid), one with renal function. Thus, 36 of the study patients (40%) did poor-
cancer, one with cancer of prostate, and one with oral Table 3. Outcomes in Patients with Involuntary Weight Loss
cancer. The next most frequent physical cause of weight
loss was gastrointestinal disease, which included mal- Outcome Physical Cause No Physical Cause
absorption, inflammatory bowel disease, severe esopha- of Weight Loss of Weight Loss
(n = 59) (77 = 32)
geal dysmotility, and diabetic enteropathy. A broad spec-
trum of conditions was associated with the weight loss in Hospitalizations, mean
the remainder of the patients. Nine percent (SD),77 1.91 ( 1.51) 1.31 ( 1.14)
had severe cardiovascular disease (all had class III or Duration of hospitaliza-
class IV congestive heart failure) with progressive weight tion, mean ( SD), d 46.4 ( 57.3) 27.2 ( 47.5)
Deaths, 77(%)+ 21 (36) 2
loss that was not diuretic induced. Eight percent were Survivors with stable or
malnourished as a result of alcohol abuse and gained increased weight, 77 34/38 27/30
weight when hospitalized. Six percent had weight loss Survivors with stable or
associated with severe obstructive lung disease (that is, increased function, 77 31/38 28/30
hypoxemia and severe exercise limitation). Four percent * P < 0.05.

5 7 0 November 1981 Annals of Internal Medicine Volume 95 Number 5

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ly during the year of follow-up observations. patients without a physical cause, the average number of
Outcome varied significantly, depending on whether abnormal test results was only 1.5, whereas in patients
patients had a physical cause of weight loss (Table 3). with a physical cause the average number of abnormal
Thus, eight of the 32 patients without a physical cause results was three (p < 0.05, chi-squared). The average
did poorly (two died, and six lost weight or had de- charge (by Stanford Hospital charges) for this evaluation
creased function), whereas 48% of the 59 patients with a would have been $364.40 for patients without a physical
physical cause did poorly (21 died, and eight lost weight cause and $389.93 for patients with a physical cause.
or had decrease in function). The difference in mortality We also assessed the findings of selected laboratory
between the two groups is statistically significant (two tests in the 59 patients with a physical cause of weight
versus 21, p < 0.05). Two patients who did not have a loss. Chest radiology was the most useful examination,
physical cause of weight loss died both suddenly and un- showing a pertinent abnormality (such as mass, infiltrate,
expectedly, one of pneumonia and the other of a cerebro- heart failure, adenopathy) in 41% of these patients.
vascular accident. Autopsy failed to show a physical Chemistry tests showed an important abnormality 22%
cause of weight loss in either patient. of the time (primarily abnormal liver function test find-
Patients who survived did well: Over 80% of the survi- ings). The blood count was abnormal in 14% (usually
vors (55 patients) in the total group either maintained or anemia), and the urinalysis was abnormal in 3%. All
improved their functional status and weight during fol- urinalyses with abnormal findings showed evidence of di-
low-up. abetes and thus duplicated the results of the blood sugar
When we compared the 36 persons who died or clini- measurement. Sixty-six percent of these patients had at
cally deteriorated with the 55 who remained stable or least one abnormal screening test (sensitivity = 0.66).
improved during the study we found five attributes that Of the tests done besides screening tests, the upper gas-
were significantly associated with outcome during the fol- trointestinal series radiograph had the highest yield.
low-up period: age, diagnosis, initial functional status, re- Twenty percent (12 patients) of the patients with a phys-
sults of initial screening tests, and weight during the year ical illness had an abnormal gastrointestinal series radio-
before weight loss. Thus, 13 of the patients who did poor- graph (usually evidence of ulcer disease or esophageal
ly were over 80 years old compared to three of those who disease). All the patients with an abnormal gastrointesti-
did well (p < 0.005, chi-squared). Thirteen of the per- nal series radiograph had symptoms suggestive of gastro-
sons who did poorly had cancer, whereas three of those intestinal disease. Altogether, 49 of the 59 patients
who did well had this diagnosis (p < 0.005, chi- (83%) with a physical cause of weight loss had abnormal
squared). Ten of the patients who did poorly needed as- findings on screening test or abnormalities on gastrointes-
sistance walking when they entered the study. Only two tinal series radiograph. Twenty of the 32 patients without
of the patients who did well were this disabled (p < 0.01, a physical cause of weight loss, however, had all normal
chi-squared). Forty-one of the persons who did well had findings on screening tests (false-positive rate = 0.37).
completely normal findings of screening tests; none of the In nearly every case, physical causes of weight loss
patients who did poorly had normal findings on screening were readily apparent to the physicians caring for the
tests (p < 0.001, chi-squared). Finally, nine of the per- patients. Thus, the mean duration from the beginning of
sons who did well had weighed more than 90.7 kg in the the evaluation to the diagnosis of a physical cause of
year before their weight loss. None of the patients who weight loss was 15.1 days (range, 1 to 183 days, median 6
did poorly had weighed this much (p < 0.01, chi- days). Longer than 30 days was needed for diagnosis in
squared). six patients (10%). Two patients (one with a gastric ul-
cer, the other with carcinoid) were observed for a period
DIAGNOSTIC E V A L U A T I O N OF P A T I E N T S W I T H (40 and 52 days) before a decision was made to do the
W E I G H T LOSS definitive diagnostic test (gastrointestinal series radio-
Study patients received a large amount of medical care. graph and colonoscopy). Three patients (all with lung
Eighty-eight percent of the patients were hospitalized at cancer) had their diagnosis delayed (51, 80, and 183
least once during the study (1.7 hospitalizations per pa- days) because abnormalities on the initial chest films
tient, mean length of stay 39.6 days). Patients with a were not noted and acted on. Retrospective analysis of
physical cause of weight loss averaged 46.4 days the chest films after the diagnosis had been made in these
(SD 57.3, median = 30 days) in the hospital, whereas patients showed clear-cut abnormalities. All died within
patients without a physical cause averaged 27.2 days 7 months of their presentation with weight loss. One pa-
(SD 47.5, median = 9 days) in the hospital. tient with lung cancer may be considered to have had a
Patients had numerous tests as part of their initial eval- truly occult malignancy. He had received a thorough
uation. Although all patients had weight loss, evaluation evaluation during his first hospitalization for weakness
was often directed at other problems as well (such as and weight loss and been discharged with a diagnosis of
pain, gastrointestinal symptoms, fever). We tried to re- depression. He was readmitted 4 months later with fur-
cord in the initial evaluation findings of those tests that ther weight loss and back pain. A new lytic lesion in his
were directed at the patient's weight loss. Each patient spine was found to be adenocarcinoma. When he died 3
underwent an average of 14.5 tests (14.4 for patients weeks later the primary cancer of the lung was identified
without a physical cause and 14.6 for patients with a at autopsy. It never had been noted on any chest film. In
physical cause). We counted the SMA-12 as one test. In patients without a physical cause of weight loss a mean
Marion eta/. Involuntary Weight Loss 571

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Table 4. Linear Discriminant Function for Weight Loss leaving-one-out method (5, 6)to test our rule. This
method involves recomputing the discriminant rule a se-
Attribute Score* ries of times, each time with one patient left out of the
Less than 20 pack-years of smoking +3 calculation. The rule is then applied to that patient, and
No decrease in activities due to fatigue +5 whether the patient has been correctly classified is deter-
Patient complaints of nausea/vomiting 3 mined. The number of misclassifications is a reasonably
Recent improvement in appetite 2 unbiased indication of how well the rule will work in
Cough that has recently changed 1
Findings of physical examination suggesting physical other settings. When this method was applied to our pop-
cause of weight loss 1 ulation, the rule had an error rate of 12%. Most misclas-
Correction factor +8 sifications involved patients without a physical cause of
Total 1-16 weight loss. Specifically, the rule misclassified nine of 32
* The attribute scores were rounded off for ease in using the rule. However, the patients without a physical cause of weight loss and 2 of
accuracy of the rule was not affected by rounding off. 59 patients (3%) with a physical cause: exactly the same
duration of 29 days (median, 10 days; range, 1 to 180 as during the initial calculations. Hence, the error rate of
days) was needed before the evaluation was considered this particular rule appears to be fairly stable.
complete.
Discussion
A DIAGNOSTIC STRATEGY FOR WEIGHT LOSS Involuntary weight loss is a common complaint. In our
One goal of this study was to develop an initial diag- medical clinic we found that nearly 8% of 1200 consecu-
nostic strategy that would quickly distinguish patients tive patients claimed that they had lost over 2.3 kg during
with a physical cause of weight loss from patients with no the previous 6 months without trying (we did not ascer-
physical cause of weight loss. Multivariate discriminant tain how many actually had documented weight loss).
analysis of all 91 patients showed six attributes (of 123 Certainly, weight loss is a matter of concern to most phy-
tested) that were significant, independent diagnostic pre- sicians. Our study supports several commonly accepted
dictors (Tables 4 and 5). All six attributes were findings beliefs concerning weight loss and refutes at least one.
of history and physical examination; findings of screening First, we found that many persons who claimed signifi-
laboratory tests were weaker predictors. Patients who cant weight loss had not actually lost weight. Almost half
had maintained the same level of activity during weight the persons considered for the study did not have weight
loss and who smoked relatively little were unlikely to loss, as documented by recorded stable weights. There
have a physical cause of weight loss. Patients who had was a group of patients, however, in whom weight loss
nausea or vomiting, a recent increase in appetite, or a could not be confirmed or refuted by available data.
cough that had recently changed (in frequency, produc- These patients were clinically indistinguishable from pa-
tivity, or severity) were likely to have a physical cause of tients with documented weight loss. All had a convincing
weight loss. Patients in whom findings of physical exami- history of weight loss (for example, change in clothing
nation suggested a physical cause of weight loss (such as size, confirmation of history by a family member, or abili-
cachexia, abdominal mass, adenopathy, thyromegaly) ty to give exact weight change). We conclude, therefore,
were also more likely to have a physical cause. A pa- that the physician should seek, but not necessarily re-
tient's discriminant score (weight loss score), was calcu- quire, actual documentation of weight loss before pro-
lated by summing the coefficients of all findings that were ceeding with further evaluation. A convincing history of
present. The higher the score, the less likely the patient weight loss may sometimes be sufficient.
was to have a physical cause of weight loss. Thus, all 26 Second, weight loss is a potentially serious symptom:
patients with a score of 6 or less had a physical cause of Twenty-five percent of the patients died within a year of
weight loss, 31 of the 40 patients with a score of 7 to 8 entry into the study, and another 15% continued to lose
had a physical cause, two of the 14 patients with a score weight or deteriorate in function. Most patients who did
of 9 to 11 had a physical cause, and none of the 11 pa- poorly had cancer or cardiopulmonary disease. In other
tients with a score of 12 or greater had a physical cause of settings with younger patients or fewer patients with can-
weight loss. With a score of less than 9 used to indicate a cer, however, the prognostic implication of weight loss
physical cause of weight loss, the sensitivity of the rule is may not be so grim.
0.97 and the false-positive rate 0.28. The two patients On the other hand, not all patients with weight loss
who had a physical cause of weight loss and a score of 9
or greater had obvious diseases: One had alcoholic liver Table 5. Performance of the Linear Discriminant Rule
disease, and the other had severe diarrhea due to diabetic Rule Patients Patients Patients in
enteropathy. Score With With N o Score Group
The discriminant rule was developed on all the study Physical Physical With a
Cause Cause Physical Cause
patients. Because the discriminant calculation creates a
rule that is optimum for the population on which it is n %
developed, testing such a rule to assess its reliability is 1-6 26 0 100
important. Because of the practical problems of prospec- 7-8 31 9 78
9-11 2 12 14
tively testing a rule in a second group of weight loss pa- 12-16 0 11 0
tients, we used a statistical techniqueknown as the
572 November 1981 Annals of Internal Medicine Volume 95 Number 5

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have a serious physical illness, given our finding of a 35% tuberculosis). A third had a normal chest roentgeno-
prevalence of no physical cause of weight loss. Of course, gram. Each of these three patients needed a second hospi-
such a conclusion depends on the validity of our diagnos- talization before the correct diagnosis was made. The di-
es. Whereas the diagnostic end point for physical causes agnosis in a fourth patient, who also had lung cancer, was
of weight loss was clear, diagnoses in patients without a not made until 51 days after his initial presentation. Al-
physical cause of weight loss were usually made by the though his initial chest roentgenogram was misinterpret-
exclusion of disease. Considering the long follow-up on ed as normal (in retrospect, it showed a hilar mass), his
these patients, we believe that this strategy was adequate symptoms and other laboratory test results convinced his
for ruling out disease. Moreover, physical causes of physicians that he had a serious illness. After hospitaliza-
weight loss were always apparent within 6 months of the tion, a vocal cord paralysis developed, leading to the cor-
initial evaluation, even in those few patients in whom the rect diagnosis. Thus, weight loss was a late symptom in
diagnosis was first missed. Hence, we believe that 6 patients with serious disease. By the time weight loss was
months of follow-up is generally adequate for excluding present, either other specific disease manifestations were
physical causes of weight loss. readily apparent or the disease was too advanced for ef-
Our findings also show the difficulty in understanding fective treatment. We therefore believe that when the ini-
the pathogenesis of weight loss. Study patients with no tial evaluation of weight loss is unrevealing, a period of
discernible physical cause of weight loss could have lost watchful waiting is generally preferable to an exhaustive
weight because of decreased caloric intake, a change in search for occult malignancy.
metabolism, or loss of calories. We did not attempt pre- We found that multivariate analysis enhanced the di-
cise estimates of caloric intake, basal metabolism, or ca- agnostic value of easily obtained clinical data. Most stud-
loric loss; such measurements should be done in future ies that have correlated clinical information with diagno-
studies of involuntary weight loss. We also occasionally sis have reported the predictive value of single clinical
found it difficult to be sure of a cause-and-effect relation attributes. Because clinicians often use combinations of
between weight loss and physical illness. Although the attributes to make a diagnosis, multivariate analysis,
relation between cancer and weight loss is well known which defines the most effective attributes and the opti-
( 7 ) , there may be multiple mechanisms of weight loss in mum relative weighting, should provide a more realistic
chronic obstructive lung disease or cardiovascular disease model for interpreting clinical data. This approach has
(8-10). We often attributed weight loss to disease when been successfully used by Goldman and colleagues (11)
changes in disease status paralleled weight gain or weight in their study of cardiovascular risk factors in surgical
loss. Although we could not always be sure of the patients and in our study (12) of the clinical usefulness
strength of the relation between diagnosed disease and of the upper gastrointestinal series radiograph. In both
observed weight loss, the high level of agreement between these studies and the present one, a group at very low risk
two independent diagnosticians indicates that our causal of a serious outcome could be defined by easily acquired
inferences would be accepted by most physicians. data. Because the decision rule requires only a history
The commonly held belief in "occult" malignancy as a and physical examination, it might have resulted in a no-
cause of weight loss was not supported by our findings. ticeable decrease in diagnostic tests for those of our pa-
By occult, we mean not apparent after the initial evalua- tients whose weight loss score placed them in a low-risk
tion. The belief in occult disease may lead to intensifica- group.
tion of the diagnostic evaluation of patients in whom ini- Because patients without other specific complaints and
tial studies are unrevealing. This phenomenon occurred a high weight loss score (9 or more) are very likely to be
in our patients without a physical cause of weight loss, free of serious disease, the physician may choose to reas-
who had the same number of tests as those with a physi- sure them and observe their clinical course. Further eval-
cal cause, albeit with fewer abnormal results. We ob- uation should center on possible psychiatric problems or
served, however, that a physical cause of weight loss was inadequate caloric intake rather than diagnostic tests for
almost always apparent after a brief evaluation. Although serious, but clinically inapparent, disease. Patients with a
extensive investigation was sometimes needed to eluci- low score (8 or less), however, should be evaluated fur-
date the exact diagnosis or extent of serious disease, it ther because the probability of a physical cause of weight
was almost never needed to ascertain whether serious dis- loss is very high. In such patients, history and findings of
ease was actually present. In almost every patient with physical examination and the initial laboratory evalua-
organic abnormalities, the initial history and findings of tion (consisting of a blood count, chest film, SMA-12,
physical and laboratory examination (blood count, chest stool for occult blood, and urinalysis) will usually sug-
roentgenogram, SMA-12, urinalysis, and stool for occult gest the diagnosis. The principal concern in using the
blood) accurately guided the physicians in deciding weight loss rule is its applicability to other populations.
whether to do tests that proved the diagnosis (for exam- Until experience in other settings has accumulated, the
ple, gastrointestinal radiography, sputum cytologic stud- weight loss rule should be used as but one piece of evi-
ies). dence among many in deciding the direction of a pa-
The diagnosis was elusive in only four of 59 patients tient's evaluation. Thus, many clinicians may still wish to
with physical causes. All four had lung cancer. Two had do screening laboratory tests in all patients with weight
obvious chest roentgenographic findings of cancer that loss rather than only in those with a screening score of 8
were initially attributed to other causes (pneumonia, old or less.
Martonetal. Involuntary Weight Loss 5 7 3

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Involuntary weight loss is a nonspecific symptom. Like preparing the manuscript, Carol Sox for programming the data analysis, and
Lynne Marton for assisting in the data entry.
fever and weakness, it may be either a manifestation of a Grant support: The Robert Wood Johnson Clinical Scholars Program and
life-threatening illness or a symptom without a disease. the Veterans Administration.
The cause of weight loss in contrast to that of fever and This paper was presented at the Thirty-Seventh Annual National Meeting
of the American Federation for Clinical Research, 10-12 May 1980, in
weakness, however, will almost always be readily appar- Washington, D.C.
ent to clinicians who use history, physical examination,
Requests for reprints should be addressed to Keith I. Marton, M.D.; Palo
and laboratory tests in a careful, discerning manner. Alto Veterans Administration Medical Center, 3801 Miranda Avenue; Palo
Alto, CA 94304.
Appendix: the Weight Loss Questionnaire
We developed an 80-item questionnaire designed to obtain References
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574 November 1981 Annals of Internal Medicine Volume 95 Number 5

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