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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.
On this page
- Specifically Recommended Tests for Screening of CFS
- Example of a Clinical Scenario Requiring Further Laboratory Testing
- Tests that are Experimental and Should Not be Used
- Additional Experimental Tests
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Blood urea nitrogen (BUN): Various renal diseases can lead to an increase in the concentration of urea in blood plasma.
- 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.
- Creatinine: Elevated levels of plasma creatinine may indicate impaired renal function.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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
- 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.
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
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