Chronic Fatigue Syndrome

Extreme fatigue that is ongoing and cannot be explained by a medical condition or has no other scientifically proven cause is called Chronic Fatigue Syndrome or CFS. Chronic Fatigue Syndrome can be detrimental to a person’s ability to perform and complete even the most basic daily or routine tasks and activities.

As there is currently no definitive test to diagnose CFS, laboratory testing is used to eliminate and provide treatment options for health conditions or disorders with similar symptoms. The CDC provides guidelines for the basic tests that should be performed, but these could be dependent on other symptoms as well as the health care practitioner managing the case.

Laboratory Tests For Exclusion Purposes

A Comprehensive Metabolic Panel (CMP) includes a variety of different tests to determine the health of organs and identify a range of health conditions such as kidney and liver disease.

A Complete Blood Count (CBC) evaluates blood disorders specifically to look for infection or anemia and other conditions.

C-reactive Protein or Erythrocyte Sedimentation rate, which acts as indicators of nonspecific inflammation in the body.

Thyroid Stimulating Hormone (TSH), including other types of thyroid testing for hypothyroidism.

Iron Studies to detect anemia or an iron deficiency.

Urinalysis to identify infections or other conditions.

Any additional tests that a medical practitioner deems necessary in identifying diseases or health conditions or excluding them as causes of the symptoms of CFS. These additional tests may include:

Antinuclear Bodies (ANA) to identify autoimmune disorders.

Lyme disease tests if the disease is suspected, and the geographical area gives cause for testing.

Rheumatoid Factor to detect Rheumatoid Arthritis.

HIV Antibody Test to identify or eliminate an HIV infection.

Cortisol Testining to identify low concentrations of cortisol as well as adrenal gland function.

SEE BELOW THE LIST OF TESTS FOR MORE INFORMATION ABOUT Chronic Fatigue Syndrome


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Serum albumin measurements are used in the monitoring and treatment of numerous diseases involving those related to nutrition and pathology particularly in the liver and kidney. Serum albumin is valuable when following response to therapy where improvement in the serum albumin level is the best sign of successful medical treatment. There may be a loss of albumin in the gastrointestinal tract, in the urine secondary to renal damage or direct loss of albumin through the skin. More than 50% of patients with gluten enteropathy have depressed albumin. The only cause of increased albumin is dehydration; there is no naturally occurring hyperalbuminemia

Serum alkaline phosphatase levels are of interest in the diagnosis of hepatobiliary disorders and bone disease associated with increased osteoblastic activity. Moderate elevations of alkaline phosphatase may be seen in several conditions that do not involve the liver or bone. Among these are Hodgkin's disease, congestive heart failure, ulcerative colitis, regional enteritis, and intra-abdominal bacterial infections. Elevations are also observed during the third trimester of pregnancy.


Antinuclear antibodies are associated with rheumatic diseases including Systemic Lupus Erythematous (SLE), mixed connective tissue disease, Sjogren's syndrome, scleroderma, polymyositis, CREST syndrome, and neurologic SLE. 

Reflex Information: If ANA Screen, IFA is positive, then ANA Titer and Pattern will be performed at an additional charge.


AST is widely distributed throughout the tissues with significant amounts being in the heart and liver. Lesser amounts are found in skeletal muscles, kidneys, pancreas, spleen, lungs, and brain. Injury to these tissues results in the release of the AST enzyme to general circulation. In myocardial infarction, serum AST may begin to rise within 6-8 hours after onset, peak within two days and return to normal by the fourth or fifth day post infarction. An increase in serum AST is also found with hepatitis, liver necrosis, cirrhosis, and liver metastasis.

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Measurement of the levels of bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematologic, and metabolic disorders, including hepatitis and gall bladder obstruction. The assessment of direct bilirubin is helpful in the differentiation of hepatic disorders. The increase in total bilirubin associated with obstructive jaundice is primarily due to the direct (conjugated) fraction. Both direct and indirect bilirubin are increased in the serum with hepatitis.

Measurement of the levels of bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematologic, and metabolic disorders, including hepatitis and gall bladder obstructive disease

Measurement of the levels of bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematologic, and metabolic disorders, including hepatitis and gallbladder obstructive disease.

The BUN/Creatinine ratio is useful in the differential diagnosis of acute or chronic renal disease. Reduced renal perfusion, e.g., congestive heart failure, or recent onset of urinary tract obstruction will result in an increase in BUN/Creatinine ratio. Increased urea formation also results in an increase in the ratio, e.g., gastrointestinal bleeding, trauma, etc. When there is decreased formation of urea as seen in liver disease, there is a decrease in the BUN/Creatinine ratio. In most cases of chronic renal disease the ratio remains relatively normal.

Increased CRP levels are found in inflammatory conditions including: bacterial infection, rheumatic fever, active arthritis, myocardial infarction, malignancies and in the post-operative state. This test cannot detect the relatively small elevations of CRP that are associated with increased cardiovascular risk.

There is a correlation between increased risk of premature heart disease with decreasing size of LDL particles. Ion mobility offers the only direct measurement of lipoprotein particle size and concentration for each lipoprotein from HDL3 to large VLDL.

Measurement of serum 25-OH vitamin D concentrations provide a good index of circulating vitamin D activity in patients not suffering from renal disease. Lower than normal 25-OH vitamin D levels can result from a dietary deficiency, poor abosrption of the vitamin or impaired metabolism of the sterol in the liver. A 25-OH vitamin D deficiency can lead to bone diseases such as rickets and osteomalacia. Above normal levels can lead hypercalcemia. This assay employs liquid chromatography tandem mass spectrometry to independently measure and report the two common forms of 25-hydroxy vitamin D: 25OH D3 - the endogenous form of the vitamin and 25OH D2 - the analog form used to treat 25OH Vitamin D3 deficiency.

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CoQ10 (Coenzyme Q10)

Coenzyme Q10 (CoQ10) is a substance similar to a vitamin. It is found in every cell of the body. Your body makes CoQ10, and your cells use it to produce energy your body needs for cell growth and maintenance. It also functions as an antioxidant, which protects the body from damage caused by harmful molecules.


A Complete Blood Count (CBC) Panel is used as a screening test for various disease states including anemia, leukemia, and inflammatory processes.

A CBC blood test includes the following biomarkers: WBC, RBC, Hemoglobin, Hematocrit, MCV, MCH, MCHC, RDW, Platelet count, Neutrophils, Lymphs, Monocytes, Eos, Basos, Neutrophils (Absolute), Lymphs (Absolute), Monocytes(Absolute), Eos (Absolute), Basos (Absolute), Immature Granulocytes, Immature Grans (Abs)

NOTE: Only measurable biomarkers will be reported.

Reflex Parameters for Manual Slide Review
  Less than  Greater Than 
WBC  1.5 x 10^3  30.0 x 10^3 
Hemoglobin  7.0 g/dL  19.0 g/dL 
Hematocrit  None  75%
Platelet  100 x 10^3  800 x 10^3 
MCV  70 fL  115 fL 
MCH  22 pg  37 pg 
MCHC  29 g/dL  36.5 g/dL 
RBC  None  8.00 x 10^6 
RDW  None  21.5
Relative Neutrophil %  1% or ABNC <500  None 
Relative Lymphocyte %  1% 70%
Relative Monocyte %  None  25%
Eosinophil  None  35%
Basophil  None  3.50%
     
Platelet  <75 with no flags,
>100 and <130 with platelet clump flag present,
>1000 
Instrument Flags Variant lymphs, blasts,
immature neutrophils,  nRBC’s, abnormal platelets,
giant platelets, potential interference
     
The automated differential averages 6000+ cells. If none of the above parameters are met, the results are released without manual review.
CBC Reflex Pathway

Step 1 - The slide review is performed by qualified Laboratory staff and includes:

  • Confirmation of differential percentages
  • WBC and platelet estimates, when needed
  • Full review of RBC morphology
  • Comments for toxic changes, RBC inclusions, abnormal lymphs, and other
  • significant findings
  • If the differential percentages agree with the automated counts and no abnormal cells are seen, the automated differential is reported with appropriate comments

Step 2 - The slide review is performed by qualified Laboratory staff and includes: If any of the following are seen on the slide review, Laboratory staff will perform a manual differential:

  • Immature, abnormal, or toxic cells
  • nRBC’s
  • Disagreement with automated differential
  • Atypical/abnormal RBC morphology
  • Any RBC inclusions

Step 3 If any of the following are seen on the manual differential, a Pathologist will review the slide:

  • WBC<1,500 with abnormal cells noted
  • Blasts/immature cells, hairy cell lymphs, or megakaryocytes
  • New abnormal lymphocytes or monocytes
  • Variant or atypical lymphs >15%
  • Blood parasites
  • RBC morphology with 3+ spherocytes, RBC inclusions, suspect Hgb-C,
  • crystals, Pappenheimer bodies or bizarre morphology
  • nRBC’s

Comprehensive Metabolic Panel


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Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency). Patient needs to have the specimen collected between 7 a.m.-9 a.m.


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Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency).

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Serum creatinine is useful in the evaluation of kidney function and in monitoring renal dialysis. A serum creatinine result within the reference range does not rule out renal function impairment: serum creatinine is not sensitive to early renal damage since it varies with age, gender and ethnic background. The impact of these variables can be reduced by an estimation of the glomerular filtration rate using an equation that includes serum creatinine, age and gender.

  • Cardio IQ Vitamin D, 25-Hydroxy, LC/MS/MS [ 91735 ]
  • Coenzyme Q10 [ 19826 ]
  • Ferritin [ 457 ]
  • Glucose [ 483 ]
  • Insulin [ 561 ]
  • Iron and Total Iron Binding Capacity (TIBC) [ 7573 ]
  • Magnesium, RBC [ 623 ]
  • Selenium [ 5507 ]
  • TSH [ 899 ]
  • Vitamin A (Retinol) [ 921 ]
  • Vitamin B1 (Thiamine), Blood, LC/MS/MS [ 5042 ]
  • Vitamin B12 (Cobalamin) and Folate Panel, Serum [ 7065 ]
  • Vitamin B2, Plasma [ 36399 ]

Elevated levels of serum erythropoietin (EPO) occur in patients with anemias due to increased red cell destruction in hemolytic anemia and also in secondary polycythemias associated with impaired oxygen delivery to the tissues, impaired pulmonary oxygen exchange, abnormal hemoglobins with increased oxygen affinity, constriction of the renal vasculature, and inappropriate EPO secretion caused by certain renal and extrarenal tumors. Normal or depressed levels may occur in anemias due to increased oxygen delivery to tissues, in hypophosphatemia, and in polycythemia vera.


Extreme fatigue that is ongoing and cannot be explained by a medical condition or has no other scientifically proven cause is called Chronic Fatigue Syndrome or CFS. Chronic Fatigue Syndrome can be detrimental to a person’s ability to perform and complete even the most basic daily or routine tasks and activities.

Even though a person is continuously fatigued, they have trouble sleeping and often wake to feel as if they have not slept at all.

Other symptoms that they may experience include:

  • Recurrent headaches
  • Pain in the joints and muscles
  • Frequent sore throat
  • Problems with memory, focus, and concentration

Not every person may experience all these symptoms and may be affected to varying degrees, which may change from day to day. In extreme cases, CFS can last for an extended period exceeding six months. A person may be able to function almost normally on days when the symptoms are mild but on bad days, may not be able to get out of bed at all. Resting and sleeping do not resolve chronic fatigue, and mental activity may increase the symptoms.

CFS can affect any person regardless of age, gender, ethnicity, or economic standing anywhere in the world. However, the disorder is estimated to be four times as prevalent in females than in males and in those between the ages of 40 and 50 years. The CDC (Centers for Disease Control and Prevention) has estimated that around 1 million people in the United States have CFS. However, only around 20% of these know that they have the disorder and have been formally diagnosed.

Currently, there is very little known about the cause of CFS. Although a single cause has not been identified, scientific research has revealed several different triggers that include the following:

  • Although no specific microbe has been attributed to the cause of CFS, viral infections like the Epstein Barr Virus may trigger the condition
  • Trauma, stress, or allergies that result in immune dysfunction may, in turn, trigger CFS
  • Malnourishment or nutritional deficiencies
  • Neurally mediated hypotension or extremely low blood pressure causing fainting may be a trigger
  • Disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, which may result from inactivity, psychiatric comorbidity, extended stress, disturbances in sleep patterns, and medication
  • After studying familial CFS patterns, researchers believe that there may be a genetic component that would make certain people more predisposed to the disorder

Current research points to CFS being a group of disorders that all result in the same symptoms rather than a singular condition. However, more research is required for scientific confirmation.

A definitive group of onset symptoms has been identified by those who have been diagnosed with CFS. In other words, specific symptoms that they experienced during a time when they had the required energy to function and complete routine tasks. It has been concluded that around 75% of the time, CFS patients experience what appear to be flu-like symptoms. In other patients, CFS followed an extended or extreme period of mental or physical stress. The symptoms of CFS also develop slowly, resulting in a gradual decline in energy levels and overall wellbeing.

There are, however, several illnesses, diseases, and health conditions that may present with a similar set of symptoms and side effects but must be distinguished from CFS. These conditions are the underlying cause of chronic fatigue and may be short or long-term. Some diseases that may present with chronic fatigue but must exclude a diagnosis of CFS include:

  • Hypothyroidism or thyroid that is under-performing
  • Mononucleosis commonly called mono
  • Psychological disorders or mental health conditions
  • Eating disorders like anorexia or bulimia
  • Cancer and cancer treatments
  • Autoimmune diseases
  • Infection
  • Abuse or addiction to substances such as drugs and alcohol
  • Side effects or reactions to prescription medications
  • An inability to achieve enough uninterrupted sleep

Unfortunately, there is currently no single evaluation or test that can be used to diagnose CFS accurately. The signs and symptoms of the disorder are used as qualifying criteria to reach a diagnosis.

Signs And Symptoms Of CFS

On conjunction with a panel of international expert researchers, the CDC have established a definition for Chronic Fatigue Syndrome and a list of signs and symptoms that therefore define the disorder:

  • Severe chronic fatigue must last for a minimum period of 6 consecutive months or longer without any known medical conditions having been previously clinically diagnosed
  • The ability to perform basic or routine daily tasks must be severely affected

A minimum of four of the following eight symptoms must occur during the six-month period, either ongoing or on a recurring basis:

  • An inability to concentrate, shortened attention span, and impaired short-term memory
  • Frequent or persistent sore throat
  • Lymph nodes in the neck or armpits that are sore and tender
  • Pain in muscles
  • Multiple joint pain that is unaccompanied by inflammation (swelling) and/or redness
  • Unfamiliar headaches, more extreme or occurring in new patterns
  • Waking up feeling unrefreshed
  • Extreme fatigue that lasts more than 24 hours after mental or physical activity

The National Academy of Medicine Committee on Diagnostic Criteria for Myalgic Encephalomyelitis (Chronic Fatigue Syndrome) released additional diagnostic criteria in a report for CFS to improve on the existing criteria for diagnosis and care of those who are suffering from the health condition. Some of the criteria are similar or the same as those that have been outlined above. Additional criteria that medical practitioners can use to diagnose the ME or CFS accurately include:

  • Extreme fatigue must be new and be present for more than six months, defined by a specific beginning. It should not have been caused by excessive exercise and cannot be improved by resting. It must affect the ability to perform basic daily activities such as work, school personal hygiene to a certain degree.
  • It must negatively impact general wellbeing and present with a general feeling of malaise (illness), which is increased after expending energy

One of the following symptoms should also be present at least 50% of the time, and it must be determined how severe and how often they occur:

  • Cognitive Impairment resulting in an inability to concentrate for a period of time, a short attention span as well as problems with memory
  • Orthostatic Intolerance is feeling dizzy or light-headed or having heart palpitations when rising from a sitting or resting position that could result in faintness or fainting

The less common side effects and symptoms of CFS include:

  • Gastrointestinal conditions such as abdominal pain, bloating, loss of appetite, nausea, and/or vomiting
  • Sensitivity or an adverse reaction (allergic reaction) to certain foods, odors, sounds, medications, or chemicals
  • Night sweats or chills
  • Constant or consistent (chronic) coughing
  • Anxiety and/or depression
  • Frequent urination
  • Sensitivity to cold and heat
  • Lowered body temperature
  • Dry mouth and eyes
  • Earache
  • TMJ (Temporomandibular Joint) dysfunction or pain in the jaw
  • Mild fever
  • Stiff joints, particularly in the mornings
  • A sensation of numbness, tingling, or burning in the extremities (hands and feet) and the face
  • Shortness of breath

Tests For CFS

As there are currently no specific blood tests, imaging scans, or other means of an accurate diagnosis for chronic fatigue syndrome, diagnosis is one of exclusion. This means that all illnesses, disease, or other health conditions that may present with similar symptoms must be excluded before arriving at a diagnosis of CFS.

Diagnosis will, therefore, involve the following:

  • Detailed documentation of the medical history of a patient
  • A thorough medical examination
  • Performing cognitive function tests
  • Excluding any other conditions that may be causing or aggravating fatigue as well as providing treatment for those conditions that can be treated
  • Ensuring that the condition fulfills the criteria to meet the CDC definition and/or National Academy of Medicine criteria
  • Monitoring of a patient over a period of time to evaluate whether there may be any other underlying causes

Classification of idiopathic or unknown chronic fatigue will be made should the condition fail to meet the CDC definition or the National Academy of Medicine criteria or where the symptoms are not severe enough to warrant a diagnosis of CFS.

As there is currently no definitive test to diagnose CFS, laboratory testing is used to eliminate and provide treatment options for health conditions or disorders with similar symptoms. The CDC provides guidelines for the basic tests that should be performed, but these could be dependent on other symptoms as well as the health care practitioner managing the case.

Laboratory Tests For Exclusion Purposes

A Comprehensive Metabolic Panel (CMP) includes a variety of different tests to determine the health of organs and identify a range of health conditions such as kidney and liver disease.

A Complete Blood Count (CBC) evaluates blood disorders specifically to look for infection or anemia and other conditions.

C-reactive Protein or Erythrocyte Sedimentation rate, which acts as indicators of nonspecific inflammation in the body.

Thyroid Stimulating Hormone (TSH), including other types of thyroid testing for hypothyroidism.

Iron Studies to detect anemia or an iron deficiency.

Urinalysis to identify infections or other conditions.

Any additional tests that a medical practitioner deems necessary in identifying diseases or health conditions or excluding them as causes of the symptoms of CFS. These additional tests may include:

Antinuclear Bodies (ANA) to identify autoimmune disorders.

Lyme disease tests if the disease is suspected, and the geographical area gives cause for testing.

Rheumatoid Factor to detect Rheumatoid Arthritis.

HIV Antibody Test to identify or eliminate an HIV infection.

Cortisol Testineg to identify low concentrations of cortisol as well as adrenal gland function.