Diagnosis: Diagnostic Testing
The Role of Laboratory Tests in
Chronic Fatigue Syndrome
Current diagnosis of chronic fatigue syndrome (CFS)
is based primarily
on whether or not the patient's symptoms fit the case definition of the condition established by the Centers
for Disease Control and Prevention (CDC). So laboratory testing in the person suspected of having CFS
should be conducted for two reasons: to exclude other plausible causes for the patient's symptoms and
to identify disorders that are con-current or that may contribute to poor health.
The authors of the 1994 CDC criteria
for CFS closely studied the
tests most helpful in excluding other causes of chronic fatigue and
settled on the battery shown below1.
Unfortunately, there is no one diagnostic
test that can be recommended
at this time, although research is underway. Some studies have actually demonstrated the futility of performing
more extensive studies in making the diagnosis of chronic fatigue syndrome2.
Of course, if disorders with overlapping
symptoms are suspected,
then specific studies should be obtained to confirm or rule out those diagnoses. For example, a person
with suspected systemic lupus erythematosis should have antibody and complement studies performed, and
a person suspected of multiple sclerosis should have an MRI, lumbar puncture or measurement of evoked
potentials. It is beyond the scope of this article to discuss the differential diagnosis of chronic fatigue
syndrome in detail, but the chart below provides
a list of diagnoses that have many features in common with CFS, and these should
be excluded by history, examination and appropriate testing.
In the past, many researchers tested
for immune status, infectious
agents and disorders of the endocrine or central nervous systems. However, with experience we have learned
that it is no longer necessary to perform such studies unless the patient is clearly informed of the investigational
nature of the tests, the testing is done as part of a protocol-based research study or the diagnosis is
We know, for example, that the hypothalamic-pituitary-adrenal
is suppressed in CFS3, which leads to low 24-hour cortisol levels, flat ACTH response curve,
low growth hormone (somatomedin, IGF-1) levels. Numerous studies have demonstrated punctate T2 weighted
lesions within the cerebral convexities of CFS patients4&5, and SPECT scanning has repeatedly
a pathological decrease of blood flow in the cerebrum and mid-brain6. We also know that the
is characteristically up-regulated in CFS, but that natural killer cell activity is typically low. As
a result, latent pathogens may not be fully suppressed, and serology for herpes viruses (like the Epstein
Barr virus), chlamydia species or mycoplasma, for example, may show reactivation or positivity more commonly
in persons with CFS than in the general population.
So, aside from the exclusionary tests
mentioned above, what should
you order when CFS is suspected? I personally tend to order an antinuclear antibody (ANA), a Lyme serology
(ELISA with a reflex Western Blot for borderline or positive tests), tilt table testing for dysautonomias
and polysomnography. The first two should be strongly considered if there is any suggestion of frank arthritis
or the patient has frequented a Lyme-endemic area. The tests are relatively inexpensive and lupus and
Lyme disease so closely mimic CFS and are so imminently treatable that the diagnoses should not be missed
for the sake of conserving resources.
The downside, however, is that borderline
ANA and Lyme ELISA tests
are not uncommon in CFS7, and such indeterminate results may trigger both anxiety and more
Tilt table testing is used to demonstrate
the dysautonomia that occurs
in up to 96% of persons with CFS8, including neurally mediated hypotension, symptomatic orthostatic
and milder forms of orthostatic intolerance. These dysautonomias are treatable, and appropriate therapy
can significantly reduce the symptoms of CFS. Unfortunately, one cannot clinically predict who will or
will not have a positive test, nor can one predict the type of dysautonomia9, so virtually
can benefit from the study.
Tilt table testing is relatively expensive
and must be performed
properly at centers with empathy and good understanding of the orthostatic intolerance seen in CFS8.
this procedure may not be available to all patients.
There is a high incidence of sleep
apnea and other sleep disorders
occurring in conjunction with CFS. The recognition and management of such sleep disorders can markedly
improve symptoms and prevent secondary complications, such as weight gain, hypertension and even stroke.
Patients at high risk (history of snoring, apneic periods, gasping awake, obesity and hypertension, short
neck and/or retrognathism) should be strongly considered for sleep monitoring.
While they are admittedly less accurate
inpatient studies, home sleep
monitoring studies can be quite helpful in ruling out sleep apena they are less expensive, much
less intrusive and frequently available from sleep centers. The clinician will have to rely on a history
from the patient or family if restless legs, periodic leg movements or myoclonus are suspected, however,
because home monitoring generally does not include any muscle monitoring11.
Fukuda K et al. The chronic
fatigue syndrome: a comprehensive approach to its definition and study. Annals of Int Med.1994; 121(12):953-59.
Lane TJ, Matthews DA, Manu P.
The low yield of physical examinations and laboratory investigations of patients with chronic fatigue.
Am J Med Sci.1990;299:313-18.
Demitrack MA et al. Evidence
for impaired activation of hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome.
J Clin Endocrinol Metab.1991;73:1224-34.
Buchwald D et al. A chronic
illness characterized by fatigue, neurologic and immunologic disorders, and
active human herpesvirus type 6 infection. Ann Intern Med.1992:116 (2):103-13.
Schwartz RB et al. Detection
of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and
SPECT. Am J Roentgenology.1994;162:935-41.
Schwartz RB et al. SPECT
imaging of the brain: comparison of findings in patients with chronic fatigue
syndrome, AIDS dementia complex, and major unipolar depression. Am J Roentgenology.1994;162:943-51.
Bates DW et al. Clinical
laboratory test findings in patients with chronic fatigue syndrome. Arch Int Med.1995;155:97-103.
Bou-Holaigah I et al. The
relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA.1995;274:961-67.
Personal communication with Dr. Peter
Rowe at Johns Hopkins University, Baltimore, Md.
Buchwald D et al. Sleep
disorders in patients with chronic fatigue syndrome. Clin Infect Dis.1994;18 (1):568-72.
Victor LD. Obstructive sleep apnea.
Am Fam Phys.1999;60 (8):2279-86.
practices internal medicine at the Hunter-Hopkins Center in Charlotte, North
Carolina.He is also a Clinical Associate
Professor of Family and Community Medicine atDuke University.
Tests and Reasons
Complete blood count (CBC)
Helps rule out anemia, leukemia and other blood disorders as well as collagen vascular disorders such
Confirms normal blood sugar, electrolytes, renal and liver
and bone metabolism and serum proteins.
Confirms normal thyroid function, a common cause of
muscle aches and fatigue.
General indicator of inflammation, infection and collagen
and possibly collagen vascular disorders.
Conditions that share some symptoms with CFS
Exposure to toxic chemicals, heavy