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Screening tests for detecting common exclusionary conditions
When a patient visits a physician with a complaint of severe fatigue,
the physician should first have the patient describe in detail exactly
how he/she is feeling, when the illness began, whether he/she is
eating normally, and so forth. A brief physical examination will also
be conducted (e.g., temperature, blood pressure.) On the basis of the
information obtained, the physician might order a series of tests
designed to provide a generalized picture of how the body is
functioning.
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Specifically Recommended Tests for Screening of CFS
The tests listed below were specifically recommended in the chronic
fatigue syndrome (CFS) case definition article by Dr. Fukuda and
colleagues to aid physicians in screening patients for CFS.
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Complete blood count (CBC): A drop of blood
contains a number of different cell types, including red blood
cells (erythrocytes), macrophages, neutrophils, basophils,
eoisinophils, B lymphocytes, and T lymphocytes, among others.
Differences in the number or appearance of any of these cell
populations might serve as an indication of some underlying
illness. The list of possibilities is far too long to delineate
here.
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Erythrocyte sedimentation rate (ESR): This measure
indicates the rate at which red blood cells settle out in a tube.
An increased rate of sedimentation can serve as sort of general
indicator of inflammation in the body.
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Alanine aminotransferase (ALT): The activity of
this enzyme is measured in blood plasma. Elevated levels of this
enzyme can be an indication of viral hepatitis and other forms of
liver disease.
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Total protein: Measurement of the total protein
concentration in plasma. Elevated concentrations reflect
dehydration, which might be attributable to vomiting, diarrhea,
Addison's disease, diabetic acidosis, and other conditions.
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Albumin: Albumin is the most abundant protein
found in blood plasma, representing 40 to 60% of the total protein.
Reduced levels of albumin may reflect a variety of conditions,
including primary liver disease, increased breakdown of
macromolecules resulting from tissue damage or inflammation,
malabsorption syndromes, malnutrition, and renal diseases.
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Globulin: Globulins are a diverse group of
proteins in the blood, and together represent the second most
common proteins (after albumin) in the bloodstream. An elevation in
the level of serum globulin can indicate the presence of cirrhosis
of the liver.
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Alkaline phosphatase (ALP): Alkaline phosphatases
are a family of enzymes that are present throughout the body.
Elevated levels of ALP are associated with liver and bile duct
disorders, and bone diseases.
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Calcium: Increased levels of plasma calcium may
indicate the presence of malignant disease or hyperparathyroidism.
Less commonly, it could reflect thyrotoxicosis, vitamin D
intoxication, the use of thiazide diuretics, sarcoidosis, and other
disorders. Reduced levels of calcium may reflect vitamin D
deficiency, renal disease, hypoparathyroidism, magnesium deficiency
and other disorders.
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Phosphorus: Increased levels of plasma phosphate
ion may indicate imminent renal failure, hypoparathyroidism,
acromegaly, excessive phosphate intake, and vitamin D intoxication.
Sharply decreased levels of plasma phosphate may reflect vitamin D
deficiency, primary hyperparathyroidism, magnesium deficiency, and
diabetic ketoacidosis.
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Glucose: Elevated blood glucose levels may be an
indication of diabetes mellitus. Lower-than-normal blood glucose
levels (hypoglycemia) can be caused in a variety of ways, often
transiently, and must be examined under specific clinical
conditions before relating this finding to any clinical disorders.
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Blood urea nitrogen (BUN): Various renal diseases
can lead to an increase in the concentration of urea in blood
plasma.
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Electrolytes: This test measures the levels of
charged ions dissolved in the blood and urine, including sodium,
potassium, calcium, magnesium, chloride, bicarbonate, phosphate,
sulfate, and lactate. Virtually all the metabolic processes in the
body are dependent on the presence of these charged ions, the
concentrations of which are tightly controlled. Deviations from
normal levels of each of these cations can reflect a wide variety
of clinical problems, too numerous to detail here.
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Creatinine: Elevated levels of plasma creatinine
may indicate impaired renal function.
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Thyroid stimulating hormone (TSH): This is a test
of thyroid function. Higher-than-normal levels of TSH may indicate
hypothyroidism and lower-than-normal levels may suggest
hyperthyroidism. In rare instances, elevated TSH levels may be
caused by pituitary tumors.
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Urinalysis: Urine may be examined for a variety of
diagnostic indicators, including amylase, bilirubin, creatinine,
sugars, g-glutamyl transferase, hemoglobin, lactate dehydrogenase,
osmolality, electrolytes, myoglobin, protein, urea, and many more.
Elevated amylase levels can indicate pancreatic disease; increased
urine bilirubin levels signal liver damage or disease; high serum
g-glutamyl transferase suggests biliary obstruction, cholangitis,
cholecyctitis and alcoholic cirrhosis; increased lactate
dehydrogenase in urine is associated with glomerulonephritis,
systemic lupus erythematosus, diabetic nephrosclerosis, and bladder
and kidney malignancies; and so forth.
Example of a Clinical Scenario Requiring Further Laboratory Testing
Patients with unusual findings in the above set of laboratory tests
probably have an underlying disorder other than CFS that the physician
may successfully diagnose with further testing. For example, if a
patient had low levels of serum albumin together with a
higher-than-normal result on the blood urea nitrogen test, kidney
disease would be suspected. The physician might then choose to repeat
the relevant tests and possibly add new ones aimed specifically at
elucidating renal disease.
However, more than 90% of patients presenting with severe fatigue will
test at normal levels for the series of laboratory tests listed above.
Assuming that there is nothing in the physical examination or in the
personal history of the patient that suggests a clear direction to the
doctor, no further laboratory testing is recommended.
Tests that are experimental and should not be used for the clinical
diagnosis of CFS
There are a number of tests that, while they may be under legitimate
investigation in CFS studies, have no proven utility in the diagnosis
of CFS. Some of these are included below.
Serologic tests
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Epstein-Barr virus (EBV): This herpesvirus is
associated with infectious mononucleosis. EBV was initially
considered the most likely candidate as the causative agent in CFS.
More recent studies make it clear that many CFS cases have no
association with EBV infection. Therefore, serologic testing for
EBV has no utility for diagnosing CFS.
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Enteroviruses: This group of viruses is named
because of their tendency to enter and infect individuals through
the gastrointestinal tract (enteron is the Greek word for
intestine), but they are mostly associated with clinical conditions
affecting the nervous system. Examples of diseases caused by these
viruses are poliomyelitis, aseptic meningitis, and encephalitis.
Some medical researchers believe that these viruses may cause
milder forms of disease in a subset of patients, resulting in
muscle weakness or fatigue rather than, for example, severe
paralytic disease. Epidemiologic studies of enterovirus infection
in CFS patients have been inconclusive, and while some
patients' fatigue might be explained by the presence of an
enterovirus, it is not associated with all or even most CFS
patients examined thus far. As such, serologic tests, polymerase
chain reaction examination of muscle biopsy specimens, and other
methods aimed at detecting enterovirus infections are not useful in
the diagnosis of CFS.
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Retroviruses: One published account reported
evidence that DNA sequences apparently similar to human T
lymphotropic virus type II (HTLV-II) could be detected in the white
blood cells of CFS patients by using a technique known as the
polymerase chain reaction, or PCR. Several efforts to repeat this
study under blinded conditions were unsuccessful. Additional
efforts indicate that none of the identified retroviruses are
associated with CFS. PCR analysis for human retrovirus DNA is not
useful for the diagnosis of CFS.
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Human herpesvirus 6: One report in the literature
suggested that human herpesvirus type 6 (HHV-6), and in particular
actively replicating HHV-6, may be associated with CFS. Subsequent
efforts to confirm an association between the active replication of
HHV-6 and CFS have been unsuccessful. HHV-6 is an extremely common
infection and is present in nearly 100% of humans by age three
years. It is not useful as a diagnostic marker for CFS.
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Candida albicans: Like HHV-6, this yeast is so
common in humans that it is virtually ubiquitous. The CDC
case-control study of CFS, among others, suggests that there is no
causal association between C. albicans and CFS. It is therefore not
useful as a diagnostic marker.
Immunologic tests
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Natural killer (NK) cell assays: Some studies have
reported a trend among CFS patients to have reduced NK cell
activity and/or reduced NK cell numbers. Some studies, including
the CDC's case-control study of CFS, have failed to demonstrate
any relationship between NK cell activity and CFS. Even those
studies that demonstrated a trend did not observe differences
between CFS patients and controls that were sufficient to permit
the use of NK cell assays as a diagnostic tool for CFS, and there
were individual CFS patients in all of those studies who exhibited
apparently normal NK cell function and numbers. As such, NK cell
assays have no value as a diagnostic marker for CFS.
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Cytokine assays: Cytokines are hormone-like
molecules produced by one cell to influence the behavior of
another. These proteins are essential to the regulation of
virtually every system in the body and are central to the
coordination of the immune system. Various reports have suggested
that elevated levels of certain immune system cytokines, e.g.,
interleukin-1 and interleukin-6, are associated with CFS. Findings
among various research groups are inconsistent—some observed
a trend toward elevated cytokines and others did not—but, as
with NK cell assays, in no case were differences observed between
CFS cases and controls sufficiently large to be diagnostic. Nor
were such elevations uniformly observed among CFS patients. No
cytokine has been identified to date that serves as a useful
diagnostic marker for CFS.
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Cell marker assays: At least one study observed an
elevation in the number of T cells expressing activation markers
among the most severely ill CFS patients. T cell activation markers
normally are increased in number on the surface of T cells during
periods when the immune system has been engaged in responding to
some infectious disease. That work has not been confirmed, and no
such trend has been observed in other studies of CFS patients. As
such, no set of immune cell markers has yet been identified that
serves as a diagnostic tool for CFS.
Imaging tests
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Magnetic resonance imaging scan: single-photon
emission computed tomography: Some CFS researchers have observed
apparent differences in the cranial blood flow between CFS patients
and controls. These studies remain unconfirmed, and imaging tests
should not be performed as a diagnostic technique for CFS.
Additional Experimental Tests
Tilt table test: This test involves strapping the patient to a table
that can be tilted at various angles. The patient's blood pressure
is measured, sometimes before and after administration of medication
that hastens the heartbeat, at several angles of inclination and
declination. In one study (see The Facts About CFS, section on
Diagnosis of CFS) most CFS patients were found to exhibit a marked
decrease in blood pressure in the tilt table test.
Page last modified on May 5, 2006