Adolescent Health Care: A Practical Guide

Chapter 35

Fatigue and the Chronic Fatigue Syndrome

Martin Fisher

The complaint of fatigue is common among adolescents. In studies of teenagers, up to 70% indicate that they are sleepy during the day (Hansen et al., 2005). In most instances, fatigue in adolescence is due to a deficit in hours of sleep. Accordingly, most adolescents sleep more on weekends, when they have time for catch-up, than they do during the week, when they are usually scheduled with multiple activities. In some instances, however, fatigue can be due to medical or psychological causes. The key to the evaluation of the adolescent with fatigue is to distinguish those cases that need merely reassurance and perhaps a change in schedule, from those who require further management for organic or psychiatric disorders or who are exhibiting signs and symptoms of the chronic fatigue syndrome (CFS).

Causes of Fatigue

Adolescent Sleep Patterns

The most common cause for fatigue in adolescents is insufficient sleep. Recent studies have demonstrated the following:

  1. Total sleep duration decreases from a mean of 10.1 hours at 9 years of age to a mean of 8.1 hours at 16 years (Iglowstein et al., 2003).
  2. Adolescents sleep as much as 2 hours less per night on weekdays during the school year than during the summer; weekend sleep is an average of 30 minutes more per night during the school year (Hansen et al., 2005).
  3. Fifteen percent of adolescents report falling asleep in the car or bus on the way to school; 25% report falling asleep on the way home (Lee et al., 1999).
  4. As adolescence progresses, bedtimes get later on both school days and nonschool days; wake-up times on weekends and holidays also get later (Millman, 2005).

Psychological Causes

In adolescents, psychological causes are responsible for most cases of fatigue that is unrelated to too little sleep and/or too much activity. Psychological causes of fatigue include:

  1. Depression
  2. Anxiety
  3. Stressful situations
  4. Other psychiatric disorders

Organic Causes

Organic causes of fatigue are infrequent during adolescence, but the differential diagnosis is very broad. Fatigue may result from any of the following:

  1. Medications, illicit drugs, and poisonings
  2. Antihistamines, sedatives
  3. Alcohol, drug use
  4. Other medications (including antidepressants and other psychotropic medications)
  5. Heavy metal intoxication
  6. Infectious diseases
  7. Mononucleosis (see Chapter 29)
  8. Hepatitis (see Chapter 30)
  9. Influenza, mycoplasma (see Chapter 29)
  10. Cytomegalovirus, parvovirus infections
  11. Chronic infectious diseases, for example, human immunodeficiency virus (HIV), tuberculosis, Lyme disease, brucellosis
  12. Bacterial endocarditis
  13. Parasitic infections
  14. Endocrine disorders
  15. Hypothyroidism, hyperthyroidism (see Chapter 9)
  16. Diabetes mellitus, hypoglycemia
  17. Addison disease, Cushing syndrome
  18. Hypopituitarism, hypoparathyroidism
  19. Systemic illness
  20. Allergies
  21. Connective tissue diseases
  22. Anemia
  23. Neoplasms
  24. Congenital heart disease
  25. Asthma
  26. Inflammatory bowel disease
  27. Renal failure
  28. Liver failure


Sleep Disorders

Although still relatively uncommon, sleep disorders are increasingly being recognized as a cause of fatigue and/or daytime sleepiness in adolescents. Included in this category are those with:

  1. Insomnia—Defined as decreased sleep quality and/or quantity due to trouble falling asleep and/or maintaining sleep. Insomnia can be:
  2. A symptom of an underlying medical or psychological disorder
  3. Due to no readily apparent cause, referred to as psychophysiological insomnia
  4. Part of a delayed sleep phase syndrome (DSPS), “a circadian based disorder in which an individual's internal circadian pacemaker is not in synchrony with internal or environmental time.” DSPS is thought to occur in up to 7% of adolescents (Millman, 2005).
  5. Obstructive sleep apnea (also referred to as sleep disordered breathing, SDB) occurs in up to 1% to 3% of adolescents (Millman, 2005).
  6. Most commonly caused by enlarged tonsils and adenoids
  7. Increasingly being reported in obese adolescents
  8. Can also be due to retrognathia or nasal obstruction
  9. Other sleep disorders, which are uncommon but which can occasionally be seen in adolescents include the following:
  10. Narcolepsy
  11. Idiopathic hypersomnia
  12. “Periodic leg movements during sleep”
  13. “Restless leg syndrome”

Chronic Fatigue Syndrome

CFS is a poorly understood and often controversial diagnosis that is seen mostly in adults but has increasingly been reported in adolescents. It involves chronic and debilitating fatigue seen in association with other symptoms. Details of this syndrome, as seen in adolescents, are as follows:


The Centers for Disease Control and Prevention has developed a working definition of CFS (Fukuda et al., 1994):

  1. Fatigue of at least 6 months duration
  2. Limits the individual to 50% of premorbid activity levels
  3. May be persistent or recurrent
  4. No other cause found to account for the fatigue
  5. Additional symptoms (four or more are required to meet the criteria for CFS)
  6. Recurrent pharyngitis
  7. Tender lymph nodes
  8. New-onset headaches
  9. Impaired memory or concentration
  10. Joint pains
  11. Muscle pains
  12. Nonrefreshing sleep
  13. Postexertion fatigue


Studies in adults and adolescents have shown the following:


Adults (Cho and Stollerma, 1992)

Adolescents (Marshall, 1999)




Mean age

35–41 yr

14–15 yr


Mostly white

Mostly white


Most employed before illness

Some with school attendance problems


0.5–14 yr before presentation

0.6–2.2 yr before presentation

Sudden onset




Patients often have many symptoms of CFS simultaneously. One study of 59 children and adolescents showed the following symptoms (Krilov et al., 1998):





Sore throat


Abdominal pain




Impaired cognition










Nausea or vomiting













No specific etiology has been determined to be the cause of the CFS. Many possibilities have been considered. It is likely that the underlying cause may be a combination of factors, including an acute infectious illness that acts as a precipitant, a background of psychological distress, and an underlying physiological vulnerability (in the cardiovascular, neurological, endocrine, and/or immune systems). It is also likely that no two individuals with CFS have exactly the same relative ratio in the combination of underlying factors. Etiologies that have been considered include the following:

  1. Infection
  2. Several infectious diseases, most notably Epstein-Barr virus (EBV) infection and influenza, can serve as the precipitant for the onset of CFS. In other parts of the world, other viral infections have been implicated as triggers for CFS.
  3. Any acute illnesses can cause an exacerbation of symptoms during the course of the syndrome.



  1. No specific infectious agent has been found to account for continuation of the symptoms.
  2. Cardiovascular system
  3. Orthostatic symptoms are common in patients with CFS (Stewart et al., 1999a).
  4. Tilt-table testing is often positive in patients with CFS.
  5. Underlying cardiovascular instability, in those with a tendency toward hypotension, may be a factor in the cause of CFS.
  6. Endocrine system
  7. Decreased hypothalamic-pituitary-adrenal axis function has been suspected as an etiology in CFS but never clearly documented (McKenzie et al., 1998).
  8. No other endocrine disorders have been consistently demonstrated in CFS.
  9. Neurological
  10. Headaches and impaired cognition are prominent symptoms in many patients with CFS.
  11. Computed tomography (CT) scans and magnetic resonance imaging (MRI) do not show abnormalities in patients with CFS.
  12. No other reproducible neurological abnormalities have been found to be a cause of CFS.
  13. Immune function
  14. Studies have shown in vitroabnormalities in lymphocyte function and cytokine production in CFS (Conti et al., 1998).
  15. Reproducible abnormalities and opportunistic infections have not been found.
  16. Treatment with immunoglobulins and other immune modulators have not shown clear benefits in CFS.
  17. Depression
  18. A history of depression is found in many adults with CFS; depression may create a psychological vulnerability necessary for the onset of CFS.
  19. Depression may be one physiological consequence of changes in the brain that occur in CFS.
  20. Depression may be a natural reaction to feeling ill and fatigued for a long time.
  21. Some have suggested that CFS is merely an alternate expression of depression.
  22. There is substantial overlap in the symptoms of CFS and depression leading to the possibility that some patients with depression will be misdiagnosed as having CFS and vice versa.
  23. Other psychological variables
  24. Separation anxiety and/or school phobia may be a factor in some children and adolescents with CFS.
  25. Some have considered CFS to be in the realm of conversion reaction.
  26. Psychosomatic symptoms may be found premorbidly in some children and adolescents with CFS.

Evaluation of Fatigue

Evaluation of the adolescent with a complaint of fatigue is aimed at distinguishing those who are merely not getting enough sleep from those who may have a specific disorder of sleep or other psychological or medical causes. A complete history and thorough physical examination, selected laboratory tests, and occasionally other studies, are performed.


The history is geared toward evaluating the adolescents' sleep patterns and activity levels; looking for evidence of medical, psychological, or sleep disorders; and determining whether a diagnosis of CFS may apply:

  1. Sleep patterns and activity levels
  2. Hours of sleep at night, naps during the day
  3. Time going to sleep, time arising
  4. Difficulty falling asleep, waking up during the night
  5. Patterns on weekdays, patterns on weekends
  6. School schedule, out-of-school schedule
  7. Alcohol use, illicit drug use
  8. Dietary patterns, caffeine intake
  9. Medical history
  10. Past medical history, review of systems
  11. Medications: over the counter, prescription
  12. History of fever, weight loss, night sweats
  13. Symptoms consistent with endocrinopathy, infection, or neoplastic process
  14. Snoring in patient or family, unexplained leg movements
  15. Psychological history
  16. Relationships with family and friends
  17. School performance and attitude
  18. Evidence of depression and/or anxiety
  19. Signs of stress at home or in school
  20. Psychiatric disorders in patient or family
  21. Acting out behaviors, social withdrawal
  22. Criteria for diagnosis of CFS
  23. Fatigue persists for >6 months
  24. Activity is limited to <50% of premorbid levels
  25. Accompanying symptoms present
  26. No other cause of fatigue
  27. Fatigue on exertion, nonrefreshing sleep

Physical Examination

Fatigue associated with nonorganic causes is usually accompanied by normal physical examination results. Important areas to examine include the following:

  1. General appearance: Evidence of chronic illness
  2. Height, weight, and body mass index (BMI)
  3. Lymph nodes: Evidence of adenopathy
  4. Thyroid gland: Presence of goiter
  5. Cardiac: Evidence of abnormal heart murmur
  6. Abdomen: Hepatosplenomegaly
  7. Extremities: Evidence of arthritis, rash
  8. Sexual maturity rating: Puberty advancement normal or not
  9. Mental status examination to identify abnormalities in mood, intellectual function, memory, and personality—in particular, signs of depression or anxiety

Laboratory Testing and Other Studies

  1. Screening tests: Most adolescents with fatigue will have to undergo baseline screening tests consisting of:
  2. Complete blood count, erythrocyte sedimentation rate
  3. Urinalysis
  4. Comprehensive metabolic panel (electrolytes, liver, kidneys)



  1. T4and thyrotropin (TSH)
  2. Mononucleosis testing (Monospot/heterophile ± EBV titers)
  3. Additional tests: As called for, based on the history and physical examination, other tests may include:
  4. Tuberculosis testing (purified protein derivative [PPD])
  5. Electrocardiogram (ECG), chest x-ray
  6. Sinus x-rays
  7. HIV testing
  8. Antinuclear antibody (ANA)/rheumatoid factor (RF)
  9. Cortisol level
  10. Lyme titers (in endemic areas or with a positive travel history)
  11. Other studies
  12. Sleep studies (polysomnography) may be performed in a sleep laboratory if a sleep disorder is suspected.
  13. Tilt-table testing may be considered in those with orthostatic symptoms, especially in CFS. However, caution is required in interpreting tilt-table testing because positive results are frequent in adolescence and are nonspecific.
  14. Neurological studies (MRI or CT of the brain) may be necessary in those with headaches or other accompanying symptoms.


General Causes of Fatigue

Guiding and managing the adolescent with fatigue follows directly from determination of the cause of the fatigue:

  1. Adolescent sleep patterns
  2. Reassurance that there are no medical or psychological problems may be provided.
  3. Guidance regarding more appropriate sleep patterns and day time schedules may be offered.
  4. Changing school start times are being considered in some local and national discussions.
  5. Medical and psychological causes
  6. Patients with mononucleosis are encouraged to return to school as soon as they are able and they should not participate in contact sports to avoid the potential of splenic rupture (see Chapter 29).
  7. Appropriate treatment is provided to those with other medical causes of fatigue.
  8. Psychological treatment is provided to those with stress, depression, anxiety, or other psychological disorders.
  9. Sleep disorders
  10. Guidance on changing sleeping patterns is provided to those with the DSPS (Table 35.1). Both the 1-day and 1-week plans require significant motivation to be successful.
  11. Use of melatonin and/or bright lights have been studied for the treatment of DSPS, but results are inconsistent, these approaches must be used with caution, they are not yet widely accepted, and effects do not appear to be long lasting (Millman, 2005).
  12. Sleep studies may be performed in those with suspected sleep disorders.
  13. Use of continuous positive airway pressure (CPAP) and/or orthodontic appliances at night, may help some adolescents with obstructive sleep apnea syndromes.

TABLE 35.1
Techniques to Reverse Sleep–Wake Cycle in Adolescents with Delayed Sleep Phase Syndrome

1-Day Plana

1-Week Planb

a Fisher R. personal communication 2005.
b Czeisler CA, Richardson GS, Coleman RM, et al. Chronotherapy: resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep 1981;4:1, Czeisler et al. (1981).

1.  Fall asleep at usual time (e.g., 4 a.m.)

2.  Set alarm and wake up 6 hr later (e.g., 10 a.m.)

3.  Remain awake all day

4.  Go to sleep at midnight (will have slept only 6 hr in last 36 hr so should be tired)

5.  Set alarm and wake up at 8 a.m. (will again need to be active to stay awake 2 d in a row)

1.  Stay awake until 3 hr after usual sleep time (e.g., go to sleep at 7 a.m.)

2.  Day 2, stay awake until 3 hr after previous bedtime (e.g., go to sleep at 10 a.m.)

3.  Day 3, go to sleep 3 hr later than previous day (e.g., 1 p.m.)

4.  Day 4, again go to sleep 3 hr later (e.g., 4 p.m.)

5.  Day 5, go to sleep 3 hr later (e.g., 7 p.m.)

6.  Day 6, go to sleep 3 hr later (e.g., 10 p.m.)

7.  Day 7, go to sleep 2 hr later (e.g., at midnight) and wake up 8 hr later (at 8 a.m.)

Chronic Fatigue Syndrome

No specific treatment has been found to shorten the course of CFS in adolescents; however, certain management approaches can help adolescents and their families cope better with the illness and decrease morbidity associated with CFS. They include the following:

  1. Explanation and reassurance
  2. Provide a detailed explanation of CFS (including etiology and management, course and outcome).
  3. Reassure patients and families that symptoms are real and generally improve with time.



  1. Guide families on minimizing “doctor shopping,” unnecessary testing, and unproven therapies.
  2. Do not turn CFS into a chronic illness with secondary problems and secondary gain.
  3. Emphasize that the prognosis for adolescent CFS has generally been shown to be substantially better than the prognosis for adult CFS.
  4. Symptomatic treatment
  5. Antidepressant medication may be used to decrease symptoms of depression in CFS but studies do not show that they change the course or outcome of the illness.
  6. Anti-inflammatory medications can be used for treatment of symptoms; medications for sleep should be used sparingly.
  7. Patients with neurally mediated hypotension and/or a positive tilt-test result may benefit from medication—an α-agonist or β-blocker, fludrocortisone, or an increase in salt and water intake.
  8. Multiple vitamins, minerals, herbs, and supplements have been tried in patients with CFS without definitive benefits.
  9. Lifestyle changes and coping skills
  10. Many adolescents with CFS require home tutoring or partial school programs to function educationally.
  11. Studies have shown graded exercise programs to be beneficial in some adolescents with CFS (Viner et al., 2004).
  12. Patients and families need to develop realistic expectations while an adolescent is experiencing the symptoms of CFS.
  13. Psychological management
  14. Studies have shown cognitive-behavioral therapy to provide benefit for some adolescents with CFS (Whiting et al., 2000).
  15. Individual and/or family therapy may also be helpful (Krilov and Fisher, 2002).
  16. Self-help groups may be more appropriate for adults than for adolescents.
  17. Follow-up care
  18. Follow-up visits are provided (every 3–6 weeks) to monitor physical symptoms and psychological issues and to provide on-going guidance and reassurance.
  19. Although adolescents with CFS generally improve over time, exacerbations may be caused by intercurrent illness, a change in schedule or stressful situations.
  20. Studies have shown that more than 80% of adolescents with CFS have significant improvement within 1 to 3 years of onset of illness; this contrasts with adults who generally have a longer course and worse prognosis (Krilov et al., 1998).

Web Sites The CDC Web site for CFS. Chronic Fatigue and Immune Dysfunction Syndrome Association of America has information for patients and families. To receive information, call its resource line at 704-365-2343, or send e-mail at NIH state of the art consultation.

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