Fatigue

Key Facts & Clinical Checkpoints – Fatigue (from Murtagh)

• Most common cause:
  • Psychological distress (e.g. anxiety, depression, somatisation disorder)
  • Peak incidence: ages 20–40
• Epidemiology in general practice:
  • Fatigue presents in 1.4 per 100 GP encounters (Australian data)
  • In one NSW study:
    • 25% of adult GP attendees reported prolonged fatigue
    • 70% of these had psychological distress
• Jerrett study findings:
  • No organic cause identified in 62.3% of patients with fatigue
  • Common findings:
    • Sleep disturbance
    • Psychosocial stress
    • Many diagnosed with psychiatric illness (depression, anxiety, bereavement)
• Sleep disorders as a key differential:
  • Obstructive sleep apnoea (OSA):
    • Affects ~2% of the general population
    • Prevalence ~10% in middle-aged men
    • Risk factors: Obesity, snoring, daytime tiredness
    • Causes periodic hypoventilation → non-restorative sleep
• Serious underlying causes to consider:
  • Endocrine/metabolic: Thyroid disorders, Addison’s, diabetes
  • Malignancy
  • Chronic infections
  • Autoimmune disorders
  • Primary psychiatric disorders
  • Neuromuscular disorders
  • Anaemia
  • Cardiovascular disease
  • Drug effects (prescribed, recreational, withdrawal)
• Clinical definition of prolonged/chronic fatigue:
  • Duration: >2 weeks
  • Features:
    • Disabling tiredness
    • Non-restorative sleep
    • Headaches
    • Musculoskeletal pain
    • Neuropsychiatric symptoms
• Sociodemographic risk factors:
  • Psychological distress
  • Female sex
  • Lower socioeconomic status
  • Fewer years of education
• Chronic Fatigue Syndrome (CFS):
  • Debilitating fatigue for ≥6 months
  • Associated with ≥50% reduction in activity levels
  • Diagnosis of exclusion (no identifiable cause)

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Seven Masquerades Checklist

1. Depression
2. Diabetes
3. Drugs
4. Anaemia
5. Thyroid disease (other endocrine)
6. Spinal dysfunction
7. Urinary tract infection (UTI)

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Pitfalls (Often Missed)

• ‘Masked’ depression
• Coeliac disease
• Chronic infection (e.g., Lyme disease)
• Incipient congestive cardiac failure (CCF)
• Fibromyalgia
• Lack of fitness
• Drugs: alcohol, prescribed, withdrawal
• Menopause syndrome

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Serious Disorders Not to Be Missed

Vascular:

• Cardiac arrhythmias
• Cardiomyopathy
• Incipient CCF

Infection:

• Hidden abscess
• HIV/AIDS
• Hepatitis B and C
• Others

Cancer:

• Any malignancy

Other:

• Anaemia
• Haemochromatosis

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Probability Diagnosis

• Stress and anxiety
• Depression
• Inappropriate lifestyle and psychosocial factors
• Viral/post-viral infection
• Sleep-related disorders (e.g., sleep apnoea)

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Psychogenic / Non-Organic

Psychiatric Disorders:

• Anxiety states
• Depression / dysthymia
• Other primary disorders
• Bereavement
• Somatisation disorder

Lifestyle Factors

• Workaholic tendencies and ‘burnout’
• Lack of exercise / sedentary lifestyle
• Mental stress and emotional demands
• Exposure to irritants (e.g., carbon monoxide, ‘lead’ fumes)
• Inappropriate diet
• Obesity
• Sleep deprivation

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Organic Causes

• Congestive cardiac failure
• Anaemia
• Malignancy
• HIV/AIDS
• Subacute to chronic infection (e.g., hepatitis, malaria)
• Endocrine disorders (thyroid, Addison’s disease, diabetes mellitus)
• Nutritional deficiency
• Kidney failure
• Chronic liver failure, chronic active hepatitis
• Respiratory diseases (e.g., asthma, COPD)
• Neuromuscular (e.g., MS, myasthenia gravis, Parkinson’s disease)
• Metabolic (e.g., hypokalaemia, hypomagnesaemia)
• Drug toxicity, addiction or side effects
• Autoimmune disorders
• Sleep-related disorders

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Unknown Causes

• Fibromyalgia
• Chronic fatigue syndrome
• Somatisation disorder
• Irritable bowel syndrome (IBS)

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Fatigue Assessment by Age Group

Age Group	Common Features	Key Causes	Assessment Tips
Children	↓ Activity, clumsiness, poor concentration, ↑ sleep duration; parental concerns dominate	Iron-deficiency anaemia, URTIs, poor diet, intestinal worms, sleep disorders	Document diet and growth; assess sleep; consider FBC if red flags (e.g. bruising, pallor)
Adolescents	Fatigue, sleepiness, academic stress, altered sleep phase, rapid developmental changes	Mood disorders, eating disorders, iron-deficiency (vegetarian/menstruating), EBV, substance use	Use HEADSSS framework; assess mental health, diet, substance use; screen for sleep and eating disorders
Young to Middle-Aged Adults	Psychosocial stress, iron-deficiency (esp. in females), mental health concerns, life-stage issues	Depression, perinatal changes, menstruation-related anaemia, menopause, poor lifestyle habits	Thorough psychosocial history; check for anaemia, stressors, reproductive health context
Older Adults	Often under-reported; multifactorial; serious conditions present atypically	Anaemia, heart failure, hypothyroidism, diabetes, COPD, polymyalgia rheumatica, dementia, depression	Detailed assessment; seek collateral history; assess nutrition, polypharmacy, frailty, cognitive changes

1. Children

• Common Features:
  • Fatigue less often reported directly by the child; parents may describe:
    • Decreased energy or endurance
    • Clumsiness or reduced coordination
    • Difficulty concentrating
    • Needing longer or more frequent naps
• Key Causes to Consider:
  • Iron-deficiency anaemia (common in growing children)
    • Risk factors: excessive cow’s milk, delayed solids, dietary restriction (e.g., autism), intestinal worms
  • Recurrent viral infections (especially in winter)
  • Sleep disorders (including obstructive sleep apnoea)
  • Rarely: malignancy (consider if pallor, bruising, weight loss)
• Assessment Tips:
  • Take a thorough dietary history and document height and weight
  • Assess sleep habits, bedtime routines, screen time
  • Consider FBC to rule out anaemia or haematological causes
  • Avoid unnecessary investigations—balance against the child’s distress
  • Address parental anxiety through reassurance and education

2. Adolescents

• Common Features:
  • Fatigue or excessive sleepiness often linked to:
    • Academic pressure, social stress, puberty-related changes
    • Sleep pattern disruption (e.g., staying up late, trouble waking)
    • Low mood or emotional dysregulation
• Key Causes to Consider:
  • Psychosocial stressors (school, relationships, identity)
  • Mood disorders: depression may present with withdrawal and fatigue
  • Eating disorders: anorexia nervosa, bulimia, binge eating
  • Nutritional deficiencies:
    • Iron deficiency in menstruating teens or vegetarians
    • Vitamin B12 (esp. if excluding animal products)
  • Substance use (alcohol, cannabis, vaping, other drugs)
  • Delayed sleep phase disorder
  • Post-viral fatigue (e.g., Epstein–Barr virus/mononucleosis)
• Assessment Tips:
  • Use HEADSSS framework (Home, Education, Activities, Drugs, Sexuality, Safety, Suicide)
  • Conduct part of the consult confidentially without parents
  • Screen for depression, anxiety, disordered eating
  • Check weight, height, BMI, and compare over time
  • Consider judicious blood tests (FBC, ferritin) based on clinical judgment

3. Young to Middle-Aged Adults

• Common Features:
  • Most common group to present with fatigue
  • Women often affected due to:
    • Multiple roles (work, parenting, caregiving)
    • Pregnancy, postpartum changes, perimenopause
  • Men may present later or only at the insistence of others
• Key Causes to Consider:
  • Iron-deficiency anaemia (especially in menstruating females)
  • Postnatal depression, perimenopausal symptoms
  • Depression, anxiety, stress, burnout
  • Poor sleep hygiene, shift work
  • Alcohol or substance use
  • Chronic fatigue syndrome (rare, diagnosis of exclusion)
• Assessment Tips:
  • Take a thorough psychosocial history
  • Explore mental health, substance use, sleep, exercise
  • Consider screening tools (e.g., PHQ-9, GAD-7)
  • Discuss menstrual patterns, family planning, sexual health
  • Blood tests: FBC, ferritin, TSH, glucose – only if indicated

4. Older Adults

• Common Features:
  • Fatigue often attributed to “normal aging” and under-reported
  • May present with nonspecific symptoms
  • More likely to have multiple contributing conditions
• Key Causes to Consider:
  • Anaemia, hypothyroidism, diabetes, heart failure, COPD
  • Polymyalgia rheumatica (especially in over-50s with morning stiffness)
  • Malnutrition, frailty, and deconditioning
  • Medication side effects or polypharmacy
  • Sleep disorders (e.g., insomnia, OSA)
  • Early dementia or late-onset depression (may manifest as apathy or fatigue)
• Assessment Tips:
  • Ask about function and sleep; assess nutrition and hydration
  • Screen for cognitive decline, mental health changes
  • Consider collateral history from carers/family if needed
  • Physical exam: look for signs of anaemia, weight loss, CHF
  • Labs may include: FBC, UEC, LFTs, TSH, glucose, CRP – depending on history

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Possible Medical Conditions → Symptom Clues

Major Depression

• Early morning wakening
• Anhedonia
• Low mood
• Poor concentration

Chronic Fatigue Syndrome (CFS/ME)

• Debilitating fatigue >6 months
• Unrefreshing sleep
• Cognitive dysfunction (“brain fog”)
• Post-exertional symptom worsening

Diabetes Mellitus

• Polyuria and polydipsia
• Weight loss
• Blurred vision
• Recurrent infections

Hypothyroidism

• Cold intolerance
• Weight gain
• Constipation
• Dry skin and bradycardia

Adrenal Insufficiency (e.g. Addison’s Disease)

• Postural dizziness
• Salt craving
• Hyperpigmentation
• Fatigue and weight loss

Myasthenia Gravis

• Fatigue worsening with activity
• Muscle weakness (especially ocular or bulbar)
• Ptosis, diplopia
• Improves with rest

Anaemia

• Generalised fatigue
• Pallor
• Exertional dyspnoea
• Tachycardia

Obstructive Sleep Apnoea (OSA)

• Excessive daytime sleepiness
• Loud snoring
• Morning headaches
• Non-restorative sleep

Systemic Lupus Erythematosus (SLE)

• Joint pain
• Malar rash
• Photosensitivity
• Proteinuria, cytopenias

Chronic Infection or Malignancy

• Persistent fatigue
• Fever, night sweats
• Unintentional weight loss
• Lymphadenopathy (if present)

Cushing’s Syndrome

• Central obesity
• Muscle weakness
• Hirsutism
• Purple striae, facial fullness

Somatisation Disorder / Anxiety

• Multiple unexplained somatic symptoms
• Fatigue with GI or neurological complaints
• Emotional distress
• Often coexists with depression or trauma history

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Selected Differential Diagnosis of Chronic Fatigue

Cardiopulmonary Causes

• Congestive heart failure (CCF)
• Chronic obstructive pulmonary disease (COPD)
• Peripheral vascular disease (PVD)
• Atypical angina

Sleep-Related Disorders

• Obstructive sleep apnoea (OSA)
• Gastroesophageal reflux disease (GORD/GERD)
• Allergic rhinitis or vasomotor rhinitis

Endocrine & Metabolic Disorders

• Diabetes mellitus
• Hypothyroidism
• Pituitary insufficiency
• Hypercalcaemia
• Adrenal insufficiency (e.g. Addison’s)
• Chronic kidney disease (CKD)
• Hepatic failure

Infectious Diseases

• Infective endocarditis
• Tuberculosis
• Infectious mononucleosis (EBV)
• Hepatitis (B, C)
• Parasitic infections
• HIV/AIDS
• Cytomegalovirus (CMV)

Inflammatory & Autoimmune Disorders

• Rheumatoid arthritis (RA)
• Systemic lupus erythematosus (SLE)

Medication/Substance-Related

• Sedative-hypnotics
• Analgesics (especially opioids)
• Antihypertensives
• Antidepressants
• Muscle relaxants
• Antibiotics
• Alcohol or substance abuse

Psychological Disorders

• Major depressive disorder
• Generalised anxiety disorder
• Somatisation disorder
• Dysthymic disorder

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. Red flags that raise suspicion of serious underlying disease
Red flags	Examples of potential serious underlying disease
Recent-onset fatigue in a previously well older patient	Malignancy Anaemia Cardiac arrhythmia Renal failure Diabetes mellitus
Unintentional weight loss	Malignancy HIV infection Diabetes mellitus Hyperthyroidism
Unexplained bleeding	Anaemia Gastrointestinal malignancy
Shortness of breath	Anaemia Heart failure Cardiac arrhythmia Chronic obstructive pulmonary disease
Unexplained Lymphadenopathy	Malignancy
Fever or night sweats	Serious infection Hidden abscess HIV infection
Recent onset or progression of cardiovascular, gastroenterological, neurological or rheumatological symptoms	Autoimmune disease (eg. rheumatoid arthritis, systemic lupus erythematosus) Malignancy Arrhythmia Coeliac disease Parkinson’s disease Multiple sclerosis Haemochromatosis

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from eTG

🧠 Key History Components

• Clarify symptom meaning:
  • Ask patient: “What do you mean by fatigue?”
  • Assess impact on daily function, exertion tolerance.
• Characterise fatigue:
  • Onset: sudden/gradual/post-infection
  • Duration and pattern over time
  • Response to rest/exertion
  • Functional impact (work, ADLs, cognition, etc.)
• Explore associated symptoms:
  • Mood, sleep, pain, weight loss, fever, etc.
• Psychosocial context:
  • Mental health screen (anxiety, depression)
  • Life stressors (work, family, social)
  • Substance use: alcohol, drugs
  • Sleep hygiene and behavioural factors
• Medication review:
  • Common fatigue-related medications:
    • Antiemetics (e.g. metoclopramide)
    • Antiepileptics (e.g. valproate)
    • Sedating antihistamines
    • Antipsychotics (e.g. quetiapine)
    • β-blockers, ACE inhibitors
• Past medical history:
  • Look for chronic conditions (e.g. autoimmune, endocrine, renal, malignancy)

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from eTG

🩺 Physical Examination Focus

• General appearance: pallor, cachexia, gait
• Vitals: hypotension, bradycardia, fever
• Weight check: weight loss?
• Lymphadenopathy or hepatosplenomegaly
• Cardiovascular: murmurs, fluid overload
• Neuro, joint, or abdominal signs if indicated

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from eTG

When and What to Investigate

📉 Avoid Overinvestigation:

• Only 4% of fatigue presentations yield abnormal pathology (Gialamas et al.).
• Tests should be guided by clinical indication.

📋 Rational Investigation Principles:

• Assess pretest probability:
  • High → test may confirm/rule out
  • Low → risk of false positives; consider watchful waiting
• Weigh test benefits vs harms:
  • Anxiety, cost, unnecessary follow-up from incidental findings
  • Environmental and health system impact (MJA 2020)

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from eTG

Basic Initial Blood Tests (If Indicated)

Test	Purpose
FBC	Anaemia, infection
Serum ferritin	Iron deficiency (even without anaemia)
TSH	Hypothyroidism screening
Fasting BGL or HbA1c	Diabetes or suboptimal glycaemic control
UEC	Electrolyte disturbances, renal dysfunction
LFTs	Liver disease, alcohol use, hepatitis
CRP or ESR	Inflammation or infection

❌ Reverse T3, fasting insulin, homocysteine, or routine zinc/copper testing not routinely indicated.

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from eTG

Watchful Waiting Strategy

• Appropriate when:
  • Low risk of serious illness
  • Recent onset, mild symptoms
• Provide support, monitor, address behavioural contributors
• Schedule review in 2–4 weeks

‘Watchful waiting’ points to discuss with patients

• Reassure the patient that no signs of serious illness are currently evident.
• Explain that fatigue often resolves with time and supportive management.
• Validate their experience: Acknowledge that their symptoms are real, distressing, and deserve attention.
• Be transparent about the limitations of testing and diagnostic uncertainty at this stage.
• Invite the patient to share any ongoing concerns or fears, including those related to missed diagnoses.
• Emphasise a structured follow-up plan:
  • Propose a review within 2 to 4 weeks,
  • Monitor for symptom progression or new red flags.
• Reinforce your ongoing support and accessibility: Let them know they can return earlier if symptoms worsen.