Download Involuntary Weight Loss: Case Series, Etiology and Diagnostic

Involuntary Weight Loss: Case Series, Etiology and Diagnostic
C. BĂICUŞ1,3, SIMONA CARAIOLA1,3, ANDA BĂICUŞ2,3, R. TĂNĂSESCU3, M. RIMBAŞ1,3
1
Colentina Hospital, Clinic of Internal Medicine, Bucharest, Romania
2
INCDMI Cantacuzino Bucharest, Romania
3
Réseau d’Epidémiologie Clinique International Francophone (RECIF)
Involuntary weight loss is an important clinical condition that has not been extensively
covered in the medical literature. Searching MEDLINE, we identified twelve case series in different
regions of the world, mostly in developed countries. Three series included ambulatory patients, while
nine studied patients from secondary care hospitals. A quarter of patients with involuntary weight loss
had a cancer, and many had psychiatric diseases.
Organic causes of involuntary weight loss are usually revealed by a basic evaluation, and a
normal result is generally reassuring. In this case it is recommended a watchful surveillance instead of
blind investigations, because the prognosis of IWL of undetermined cause is good.
On the contrary, patients with involuntary weight loss caused by cancers have a severe prognostic
due to the advanced stage of the disease. On the other way, these patients are easy to diagnose.
Key words: involuntary weight loss, unintentional weight loss, cancer.
DEFINITION
The involuntary weight loss (IWL) is an
important health problem, because 3–5% of the
patients admitted in the Internal Medicine Department
come for this problem [1–3]. In our previous study
[4], more than 400 patients were admitted for
involuntary weight loss during a 9 months period,
and a quarter of them had cancer.
The most used definition of IWL important
enough to necessitate etiological investigations is
the weight loss of at least 5% of the habitual weight
during the last 6–12 months [1].
However, we know that, in many instances,
the patient does not know the initial weight,
making the amount of weight loss impossible to
compute. Considering this, it is amazing how the
authors of the most series (half of them being
retrospective) succeeded in the inclusion of
patients, having this definition as unique criterion.
Only in two studies are mentioned additional
criteria in order to solve this problem: Hernandez
[5] requested for proofs of weight loss represented
by changes of clothes measure or confirmation by a
relative/friend, while Băicuş [4] needed only
weight loss to be among the first three reasons for
hospitalisation. As we know, self estimation of
weight loss differs from person to person, but not
randomly: patients with cancer as the cause of their
weight loss underestimate the amount of weight
ROM. J. INTERN. MED., 2009, 47, 1, 87–92
loss, while those with a psychiatric disorder
overestimate it [6]. Moreover, in one study, half of
the patients referred for weight loss did not have
any weight loss at all [7].
ETIOLOGY
IWL is a non-specific symptom, very common
in the chronic diseases. IWL, together with asthenia,
anorexia and fever are constitutional symptoms.
The most frequent causes of IWL belong to
three categories of illnesses: malignant neoplasms,
chronic inflammatory/infectious diseases, or psychiatric
diseases; there are, also, other frequent diseases as
possible etiology, as hyperthyroidism or diabetes.
However, the most important step in the etiological
diagnosis is the early difference between the first
category and the others, in order to save the life of
the patient. Meanwhile, we have no answer, yet, to
the question how far have we to proceed with more
and more invasive/expansive investigations on the
way of the etiological diagnosis.
Generally, the patient with this condition loses
his appetite, excepting a few causes of weight loss
in which the appetite is normal, or even increased: uncontrolled diabetes mellitus, hyperthyroidism, pheochromocytoma, malabsorption and dentition problems.
IWL is a clinical condition that was not well
covered in the medical literature [2][3]. There are
88
C. Băicuş et al.
not evidence based protocols or algorithms for an
efficient and cost-effective diagnosis and management
[2], probably because IWL has many possible
causes, although not so many as fever of unknown
origin has [8].
Searching MEDLINE for “involuntary weight
loss”, 137 articles are retrieved, while using
“unintentional weight loss”, one finds 141. Among
them, the vast majority are reviews and case
reports, and only a few case series. Totally, directly
on MEDLINE and in the references of the studies
found on MEDLINE, we gathered 12 case series,
6 retrospective [4][5][7][9–11] and 6 prospective
2
[12–17]. A retrospective study was performed in
Romania [4]. Most of the studies were done in
secondary or tertiary care hospitals, excepting three
[7][11][16], performed in ambulatory care. Nine
studies were performed on samples of more than
100 de patients [4][5][7][9–11][14][16][17]. Concerning
the geographical distribution, 5 studies were
performed in the USA, two in Spain and one in each
of Germany, France, Belgium, Mexico and Romania.
Among the patients admitted for IWL, a
quarter have cancer, and among them, most have
gastrointestinal cancer (Table I).
Table I
The most important case series of involuntary weight loss – etiology
Case series
Marton
1978
US
Rabinovitz
1979
Israel
Huerta
1985
Mexico
Thomson
NS
US
Levine
NS
US
Lankish
1996
Germany
Hernandez
1996
Spain
Băicuş
2003
Romania
Metalidis
2006
Belgium
Patient number
91
154
50
45
107
158
276
431
101
Cancer
20
36
10
16
6
24
38
24
22
Nonmalignant
gastrointestinal
diseases
Organic,
nonmalignant
Psychiatric
14
17
16
11
6
19
10
32
15
36
13
22
29
30
30
25
23
19
9
10
42
20
22
11
23
12
16
Unknown
26
23
10
24
36
16
5
0
28
Mortality
(months of
follow-up)
25
(12)
38
(30)
NS
9
(24)
11
(15)
32
(22)
NS
NS
16
(6)
Country
From the point of view of the family
physician or gastroenterologist, if a patient with
dyspepsia has the so-called “alarm symptoms”
among which there is weight loss, an endoscopic
evaluation must be begun, although age or the
presence/absence of these alarm symptoms have a
limited value in the diagnosis of gastrointestinal
cancer [18][19].
Lankish [14] evaluated a two stage diagnostic
algorithm for the etiology of IWL similarly to the
studies concerning fever of unknown origin. He
proposed, for the first stage, history and physical
examination, chest radiography, electrocardiography,
abdominal ultrasonography, standard laboratory
tests, and tests for hyperthyroidism and occult
blood in the faeces. Patients undiagnosed after the
first step received secondary diagnostic tests
determined on the basis of results from the first
step: tests included gastroscopy, colonoscopy,
faecal weight and fat estimations, and for cause of
malabsorption (duodenoscopy, secretin pancreozymin
testing, and enteroclysis when necessary). During
admission, the 2 step procedure achieved a diagnosis
for 132 patients (84%). During follow-up, causes
were determined for 7 of the 26 patients without a
diagnosis from the 2 step procedure.
Other studies tried to forecast the presence of
cancer as a cause of IWL, based on a score
consisting of clinical and biological variables as
age, erythrocyte sedimentation rate (ESR), white
cell count, albumin, alkaline phosphatases and
lactate dehydrogenases (LDH) [4][5][15]. Hernandez
[5] found that a patient with normal serum
albumin, LDH, alkaline phosphatases and white
blood cells has only an 8% risk to have a cancer,
while a patient with all these parameters abnormal
has a 56% risk to have a cancer (the prevalence of
cancer was 38% in his series), while in Baicus’
retrospective series [4], a patient with age>62
years, high ESR and anaemia had a 91% risk of
3
Involuntary weight loss
cancer, while a patient with age ≤62, with normal
ESR and without anaemia had a risk of 8% of
cancer (the prevalence of cancer was 24%).
The conclusion was that clinical examination
and basic laboratory values in normal range can
assure us that IWL was not caused by a serious
disease [17].
PATHOGENESIS OF WEIGHT LOSS IN CANCER
It is a common place the fact that patients
with cancer lose weight. An important weight loss
(> 5 kg from baseline weight) is an independent
factor of bad prognostic [20], and in some patients
this is the direct cause of death [21].
Few studies were dedicated to the mechanisms
of cachexia and they suggest a potentially important
role of the cytokines and other substances whose
target are the skeletal muscles.
Tumour necrosis factor-alpha (TNF)-alpha,
interleukin (IL)-1 beta and IL-6 were correlated
with weight loss in patients with lung cancer [22],
prostate cancer with metastases [23] and pancreatic
cancer [24]. In animals, on one way, the injection
of any of these cytokines induced cachexia and on
the other way the administration of anticytokine
antibodies lessened it. All these studies were
performed during the first half of the years 1990
and were not continued.
The proteolysis induction factor (PIF), a
proteoglycan highlighted in a murine model of
adenocarcinoma [25], was identified afterwards in
the urine of the patients having cancer cachexia,
unlike those without weight loss [26] or those with
nonneoplastic weight loss. The results are conflicting,
however, and other studies could not succeed in
demonstrating a link between PIF and neoplastic
cachexia in humans [27–30].
ANAEMIA IN CANCER; FERRITIN AND IRON
DEFICIENCY ANAEMIA IN GASTROINTESTINAL
CANCER
In cancer, most patients may have two kinds
of anaemia, that of chronic diseases and iron
deficiency. While the first appears in any cancer
and in inflammatory diseases that produce weight
loss too, iron deficiency anaemia appears in
gastrointestinal cancer due to occult haemorrhage.
In every eight patients with iron deficiency
anaemia endoscopically investigated, one patient
89
has cancer [31–34]. Looking at the problem from
the opposite side, a high proportion of the patients
with gastrointestinal cancer (50%) have not
anaemia when the tumour is found [35][36], so
anaemia as a diagnostic test for gastrointestinal
cancer is not sensitive at all.
Anaemia is a prediction factor for the
neoplastic etiology of IWL in all the studies, those
concerning the etiology of IWL as in those
concerning the diagnosis of gastrointestinal cancer
which showed, on one way, that the risk of cancer
is higher in patients aged more than 50, with
weight loss and iron deficiency anaemia [37][38],
and on the other way that the levels of anaemia and
serum iron and ferritin correlate with the dimensions,
localisation and the stage of the tumour [39].
Therefore, anaemia appears only at a certain
moment in the evolution of cancer and cannot be
used for the early diagnosis.
In the succession of the events which lead to
iron deficiency anaemia, the ferritin diminution
appears early, immediately after the waning of the
iron deposits in the bone marrow, and before the
appearance of anaemia (and before the appearance
of all the other changes from iron deficiency
anaemia: diminutions of the tranferrin saturation,
of serum iron, of the red cell volume and of the
haemoglobin) [40], and this allows us to hope that
ferritin would have a higher sensitivity for the
diagnosis of the gastrointestinal cancer. In fact,
ferritin is the test with the highest accuracy in the
diagnosis of iron deficiency anaemia, comparing
with the other enumerated parameters [41–43].
Ferritin was assessed in a few studies for the
diagnosis of gastrointestinal cancer, and the results
showed that it has no value as screening test [44],
probably because it lowers only when the tumour is
big enough [45]. However, in more than half of the
patients having a ferritin less than 50 ng/ml serious
lesions were found at endoscopy [46], in two
patients without anaemia, a low ferritin (<18 ngm/l)
lead to the discovery of colon cancer [47], and in
patients with anaemia, a ferritin higher than 100 ng/ml
excluded gastrointestinal cancer [48].
Ferritin was assessed in only one of the 11
studies concerning weight loss, in the most recent
[17], but it showed only that ferritin was globally
higher in patients with organic diseases (malignant
or not) than in those without organic diseases,
probably because ferritin is a marker of inflammation,
too, and sometimes a neoplastic marker. However,
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C. Băicuş et al.
ferritin was not specifically assessed for the
prediction of gastrointestinal cancer.
In conclusion, in most series, approximately a
quarter of patients with IWL had cancer, and a third
another organic disease; the remaining had mostly a
psychiatric disease, or the cause remained obscure.
An organic cause of IWL is usually revealed
by a basic evaluation, and a normal evaluation is
generally reassuring. Moreover, in this case it is
recommended a watchful surveillance instead of
blind investigations, because the prognosis of IWL
of undetermined cause is good.
4
The patients with IWL caused by cancers
have a severe prognostic (short survival time), due
to the advanced stage of the disease. Therefore,
they are easy to diagnose.
Acknowledgement. This paper was supported through a
research grant PN-II IDEI (ID_10/2008), entitled “The
assessment of the accuracy of certain biological and clinical
parameters as tests for cancer diagnosis in patients with
involuntary weight loss and the elaboration of a prediction
model”, financed by the Romanian Ministry of Education and
Research – Executive Unit for Financing Higher Education
and Scientific University Research (MEdC-UEFISCSU).
Scăderea ponderală involuntară este o problemă care nu prea a fost
acoperită în literatura medicală. Căutând pe MEDLINE, am găsit douăsprezece
serii de cazuri din diferite regiuni ale lumii, cele mai multe din ţări dezvoltate. Trei
serii au inclus pacienţi din ambulator, iar nouă au studiat pacienţi internaţi în
spitale de îngrijire secundară. Un sfert dintre pacienţii cu scădere ponderală
involuntară aveau cancer, şi mulţi au avut afecţiuni psihiatrice.
Cauzele organice ale scăderii ponderale involuntare sunt de obicei
descoperite după o evaluare simplă, iar un rezultat normal este în general
liniştitor. În acest caz se recomandă mai degrabă urmărirea decât continuarea
orbească a investigaţiilor, cu atât mai mult cu cât prognosticul scăderii ponderale
involuntare de cauză necunoscută este bun.
Pacienţii cu scădere ponderală determinată de cancer au, dimpotrivă, un
prognostic sever, din cauza stadiului avansat al bolii. Pe de altă parte, aceşti
pacienţi sunt uşor de diagnosticat.
Correspondence author: C. Băicuş
Colentina Hospital, Clinic of Internal Medicine
19–21, Şos. Ştefan cel Mare, 0202125 Bucharest, Romania
E-mail: [email protected]
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Received January 20, 2009