Fatigue and TATT

Synonym - tired all the time syndrome (TATT)

This is an extremely common presentation in General Practice. The doctor should take a systematic approach, focusing on physical, psychological and social issues with a view to discovering the true aetiology and providing rational treatment or management. There is a separate Chronic Fatigue Syndrome (CFS) article.

How common is fatigue? (Epidemiology)¹

Fatigue is a normal part of life, but it can also be a symptom of disease, including serious illnesses. Chronic fatigue occurs in all age groups, including children. Women, minority groups, and people with lower educational and occupational statuses have a higher prevalence of chronic fatigue.

Tiredness is one of the most frequent presenting complaints in primary care. The reported prevalence varies according to case definitions, methods of assessment, and study settings:

• A UK community-based postal survey of a random sample of 2474 adults from 20 GP practices, found that 50% of people with chronic disease reported feeling tired/run down as a symptom.

• Another UK population-based postal survey found 10–18% of people self-reported current tiredness/fatigue that had lasted 1 month or longer.

• A UK general practice database study (1990–2001) found that the annual incidence of new tiredness/fatigue was 1.5%.

Almost three quarters of consultations for fatigue are isolated episodes, with no follow-up consultations. Investigations are carried out in only half of patients complaining of fatigue and few of these tests show abnormal results. A diagnosis is made in less than half of patients with fatigue. Many of the diagnoses are descriptive - eg, stress. Possible underlying diagnoses include:

• Physiological causes, eg, pregnancy, breastfeeding, inadequate rest or sleep, and excessive exercise.

• Physical causes, eg, anaemia, hypothyroidism, obstructive sleep apnoea. Many other conditions may cause fatigue but rarely present with fatigue as the predominant complaint, eg, diabetes mellitus, Addison's disease, chronic kidney disease, liver failure, coeliac disease, glandular fever, carbon monoxide poisoning, long covid, or malignancy.

• Psychological or psychosocial causes, eg, depression, anxiety, bereavement, and stress.

Precipitating factors for consultation can be stressful life events (eg, work disputes, family problems, bereavement or financial difficulties) or physical illnesses (eg, respiratory tract infections).

Many adolescents have severe fatigue but the prevalence of CFS is less common. Between 34% and 41% of adolescents report feeling 'much more tired and worn out than usual.² The prevalence of CFS in children and adolescents is between 0.11% and 4%.

Symptoms of fatigue (presentation)¹

There may be physical illness, or mental illness, or it may simply be a question of lifestyle. Likely illnesses are different between older and younger patients.

Ony a minority of patients presenting with fatigue will have a serious underlying physical cause. Red flags include:

• Significant weight loss.

• Lymphadenopathy with signs of malignancy (eg, a lymph node that is non-tender, firm, hard, larger than 2 cm across, progressively enlarging, supraclavicular, or axillary).

• Any other symptoms and signs of malignancy (eg, haemoptysis, dysphagia, rectal bleeding, breast lump, postmenopausal bleeding).

• Focal neurological signs.

• Symptoms and signs of inflammatory arthritis, vasculitis (eg, giant cell arteritis and polymyalgia rheumatica), or connective tissue disease.

• Symptoms and signs of cardiorespiratory disease (eg, angina, asthma, chronic obstructive pulmonary disease, heart failure).

• Sleep apnoea.

History

• Define exactly what is meant by tiredness or fatigue:
  Is it shortness of breath on exertion? Is it mental exhaustion rather than physical? Is it present all day or just towards the end of the day? Neurological disease may present as tiredness but specific muscle groups are likely to be weak.

• Note the duration of the problem:
  Is it getting worse? Was there an apparent precipitating factor? This may have been an illness such as glandular fever or influenza, a bereavement or perhaps a spouse or partner has left and the patient has to cope alone with small children and a job.

• Ask about previous levels of energy and how these compare with the present:
  Beware of platitudes like: 'What do you expect at your age?' The active elderly person who suddenly loses energy and becomes easily fatigued has serious illness.

• Discuss whether the patient has noticed any other changes:
  This may be change in weight or appetite, polyuria and thirst or sleep disturbance. Perhaps the ankles are swollen at the end of the day and nocturia more pronounced.

• Establish whether there has been a recent start or change in medication:
  Treatments for hypertension, especially beta-blockers, can cause lethargy.

Ask systematically about bodily functions:

• Ask if weight is going up or down and discuss appetite:
  Weight gain may represent comfort eating. Contrary to popular opinion, weight gain is not very marked in hypothyroidism. Thyrotoxicosis will cause tiredness and weight loss is common. Poor appetite and loss of weight occur in depression, especially with anxiety but may also represent systemic disease. Inflammatory disease or chronic infection will cause fatigue. Fatigue is common with malignancy but it tends to accompany advanced disease rather than be a presenting feature.

• Ask if there is polyuria or nocturia:
  Diabetes mellitus is not the only condition to be considered. Chronic kidney disease may present with lethargy and polyuria from failure to concentrate urine.

• Ask about menstruation, if applicable:
  Hypothyroidism may cause menorrhagia but as a cause it is uncommon. Menorrhagia may lead to non-anaemic iron deficiency or iron-deficiency anaemia. The patient may have failed to notice that her period is overdue and tiredness is due to pregnancy.

• Establish whether the bowel habit has changed:
  Bowels are often sluggish in depression or a change of bowel habit may indicate malignancy and, with it, anaemia.

• Ask about sleep:
  The early morning waking of an anxious depression is characteristic but in a retarded depression sleep may be excessive. Perhaps sleep is disturbed by the demands of young children or caring for an elderly relative.

• Ask about lifestyle:
  

  • Excessive consumption of alcohol:
    This may be a coping mechanism or an underlying cause, especially if cirrhosis or other alcohol-related problems are developing. If alcohol is being used as a coping mechanism it is likely to aggravate rather than alleviate the problem.

  • Drug taking:
    The problems of prescribed medication have been mentioned. Patients may be surprised to learn that alternative or natural remedies are just as likely to have side-effects. Because a treatment has not been adequately researched does not mean that there are no adverse effects. Illicit drugs are a more likely problem, especially amphetamines and cocaine. It is no longer appropriate to regard cannabis as a 'safe drug', especially if taken in large amounts.

  • Work:
    Perhaps very long hours are worked or the addition of parental or caring responsibilities makes it a very arduous week. Sometimes people do shift work with frequent changes of shift between early, late and even night work. The role of the pineal gland and circadian rhythms is very interesting but, constantly changing the pattern of waking and sleeping with frequent changes of shift upsets the functioning of the brain and endocrine system.

• Discuss whether there has been any significant event in the patient's life that may have sparked this episode:
  Now is the time to ask: 'Is there anything that you think may have caused all this?'

Examination

• Look at the patient:
  What do you see? Is this someone who has lost weight recently and looks systemically unwell? Do you see anxiety, tiredness or sleep deprivation? Do you see someone with the cares of the world? There may be ankle oedema from congestive heart failure although by far the most common cause is dependent oedema, especially in overweight women.

• Examination of the pulse may be revealing:
  A slight tachycardia may occur with anxiety and stress. Anaemia and thyrotoxicosis will produce a bounding, hyperdynamic pulse. Heart failure leads to sympathetic overactivity and tachycardia. Bradycardia may be found in hypothyroidism but is more likely from coronary heart disease. The irregular pulse of atrial fibrillation and flutter is easily recognised.

• Weigh the patient and record body mass index (BMI):
  Note also any comment that the patient may make about weight rising or falling. Tiredness and fatigue may be the result of carrying all those extra kilograms around. Loss of weight should lead to the suspicion of systemic disease.

• Further examination should be directed by clinical suspicion from history and examination so far.

Differential diagnoses

• Depression.

• Obesity.

• Obstructive sleep apnoea.

• Poor sleep pattern; hard work; stress.

• Treatment with a sedative; caffeine withdrawal.

• Chronic fatigue syndrome.³

• Any physical illness may be associated with fatigue, particularly anaemia; iron deficiency; cancer; renal disease; liver disease; heart failure; thyroid disease; diabetes; autoimmune disease.

Investigations¹

• Urinalysis for glucose and albumin screen for diabetes and renal disease respectively.

• FBC checks for anaemia:
  

  • If anaemia is found, the cause will need investigation.

  • Routine testing for B12 and folate is not recommended but should be tested if FBC shows macrocytosis.

• U&E and creatinine are basic tests that could demonstrate unsuspected renal disease. There may be weakness and lethargy from hypokalaemia due to laxative abuse and purgation.

• Random/fasting blood glucose

• LFTs are also a good baseline test. The pattern of abnormal LFTs may suggest alcohol misuse. There may be subclinical hepatitis or metastatic disease in the liver.

• Other tests may include ESR, CRP and monospot test for glandular fever.

• TFTs are not routinely indicated in younger patients unless there is clinical suspicion but in older patients there is more likely to be unsuspected abnormality.

• Other investigations to consider include:
  

  • IgA tissue transglutaminase (coeliac disease).

  • Bone biochemistry, especially if 60 years of age or older.

  • Serum ferritin in women of child-bearing age (there is limited evidence that iron supplementation is effective even in the absence of anaemia).

  • Testing for vitamin D deficiency, by bone biochemistry and serum 25-hydroxycolecalciferol concentration if the person is at risk because of failure to spend time outdoors or regular use of sunscreens, inadequate diet, or reduced gut absorption.

  • HIV test if the person is at risk.

  • Hepatitis serology if the person is at risk.

  • Testing for tuberculosis (chest radiography and sputum samples) pending referral if the person is at risk.

If the doctor thinks that the patient is depressed but is uncertain or the patient is sceptical about the diagnosis, a validated questionnaire such as the Patient Health Questionnaire (PHQ-9) may be a useful tool.

Fatigue treatment and management

Although many patients may have little wrong medically, remember that in some there may be serious underlying disease and it is imperative that the patient does not think that you see them as a time waster or a hypochondriac. Take them seriously. Be systematic and see this consultation as a challenge to your clinical skills rather than an imposition. Management will depend upon cause.

Physical

• Physical problems such as diabetes, heart failure, anaemia or other systemic disease need appropriate management.

• Iron supplementation should be considered for menstruating women with unexplained fatigue who do not have anaemia but do have low ferritin levels.

• Fatigue and somnolence may be associated with respiratory failure and carbon dioxide retention.

• Obstructive sleep apnoea is associated with somnolence, lethargy and poor concentration. Loss of weight is beneficial.

• There is evidence that physical activity and psychosocial interventions provide benefit in relation to self-reported fatigue in adults with rheumatoid arthritis.⁴

• Aerobic exercise is beneficial for cancer-related fatigue associated with solid tumours during and post-cancer therapy.⁵

• There is a lack of robust evidence for interventions to manage fatigue in the advanced stage of progressive illnesses such as advanced cancer, heart failure, lung failure, cystic fibrosis, multiple sclerosis, motor neurone disease, Parkinson's disease, dementia and AIDS.⁶

• The management of medically unexplained physical symptoms (MUPS) involves collaborative approaches between doctor and patient to identify problems:
  

  • There has to be assessment of medical importance of the symptoms, and readiness of the patient to initiate change of behaviour.

  • Negotiated treatment goals and outcomes, gradual physical activity and exercise prescription are all beneficial.

  • In addition, efforts should be made to teach and support active rather than passive coping with the symptoms.

Psychological

• Psychological distress is common with lethargy and fatigue and it is difficult to ascertain if this is the primary cause of the complaint or the result of it.

• Management of underlying or contributing psychological disorders may be required - eg, depression, anxiety.

Lifestyle

• The doctor may help the patient to identify social and lifestyle issues that are responsible in part or in whole.

• The patient may be in a position to address them but, even if they are unavoidable, the mere fact that someone has discussed them and lent an empathetic ear can be therapeutic.

• Drug or alcohol misuse may need to be addressed.

Even if no cause has been found, the patient may be reassured that a diligent search has failed to find one. Hence, the patient may be happy to await spontaneous resolution. A therapeutic trial of antidepressants may be worthwhile.

Prognosis

In primary care, between a third and a half of people with tiredness/fatigue as a major or concurrent symptom recover within one year. Factors associated with an increased likelihood of recovery, or with faster recovery, include:¹

• Male.

• Reduced severity and duration of fatigue.

• No expectation of fatigue becoming chronic.

• Perception of better general health.

• Lower levels of pain.

• No carer responsibilities.

• Good social support.

• Better mental health.

• Willingness to attribute fatigue is psychological factors.