What causes generalized tiredness?

Causes of Generalized Tiredness

Generalized tiredness most commonly stems from treatable medical conditions (anemia, thyroid dysfunction, cardiac dysfunction), psychological factors (depression, anxiety), sleep disturbances, medications, and nutritional deficiencies—with serious organic disease being rare (4.3%) and depression being the most prevalent identifiable cause (18.5%). 1, 2

Primary Medical Causes to Evaluate

Endocrine and Metabolic Disorders

• Thyroid dysfunction is one of the first and most important causes to investigate, as hypothyroidism frequently presents with fatigue and nonspecific symptoms 3, 1, 4
• Cardiac dysfunction should be assessed, particularly in patients who received cardiotoxic treatments or have cardiovascular risk factors 3, 1
• Anemia is a common treatable cause, occurring in approximately 2.8% of patients presenting with tiredness 1, 2
• Other endocrine abnormalities including pituitary, parathyroid, and adrenal hormone dysfunction can manifest as fatigue 4
• Metabolic abnormalities such as hyper- or hypoglycemia, dyslipidemia, and electrolyte imbalances contribute to fatigue 1, 4

Serious Organic Disease

• Malignancy is rare, occurring in only 0.6% of patients presenting with tiredness 2
• Serious somatic disease overall affects only 4.3% of patients with tiredness—notably, this prevalence is identical to patients without tiredness complaints, suggesting the association may not be causal 2
• Extensive investigations are only warranted when specific findings emerge from history or examination, such as unintentional weight loss, pulmonary complaints, or pain 3, 2

Psychological and Behavioral Factors

Mental Health Disorders

• Depression is the most prevalent identifiable cause, affecting 18.5% of patients with tiredness—and is significantly more frequent among those complaining of tiredness compared to those without this symptom 2
• Studies show 25-33% of patients with fatigue also experience depression 1
• Anxiety frequently accompanies fatigue and requires specific assessment 1
• Emotional distress can both cause and exacerbate fatigue symptoms 1
• Chronic stress with physical and psychological manifestations is a common underlying factor, though patients often lack awareness of stressors or conflicts 5

Sleep Disturbances

• Sleep disorders affect 30-75% of patients with fatigue, ranging from hypersomnia to insomnia 1
• Poor sleep hygiene—including irregular sleep schedules, daytime napping, and caffeine/alcohol consumption before bed—contributes significantly 1
• There is a strong correlation between fatigue and sleep quality, with diminished sleep quality requiring investigation using validated tools like the Pittsburgh Sleep Quality Index 3

Medication and Substance-Related Causes

• Medication side effects including sedation are common contributors to fatigue 3, 1
• Prescription and over-the-counter medications or supplements should be systematically reviewed 3
• Alcohol and/or drug abuse are associated with emotional distress, poor sleep quality, and anxiety 3

Nutritional and Activity-Related Factors

Nutritional Deficiencies

• Weight changes, caloric intake alterations, and electrolyte imbalances can contribute 1
• Specific deficiencies linked to fatigue include vitamin B6, B12, folate, ferritin, zinc, vitamin D, magnesium, copper, phosphate, and calcium 3, 6
• Even well-nourished patients may harbor vitamin and mineral deficiencies, particularly those with chronic conditions 3

Physical Activity

• Decreased physical activity worsens fatigue symptoms 1
• Conversely, regular physical activity can help reduce fatigue in individuals with no clear organic cause 6, 7

Pain and Symptom Clustering

• Pain often clusters with fatigue and requires effective treatment as part of comprehensive management 1
• Fatigue rarely occurs in isolation and frequently presents with other symptoms 1

Clinical Pearls

Laboratory results affect management in only about 5% of fatigue cases, but core testing remains essential to rule out treatable causes 1, 7. The recommended initial workup includes: complete blood count, thyroid-stimulating hormone, basic metabolic panel, liver function tests, and inflammatory markers like C-reactive protein 1. If initial results are normal, repeat testing is generally not indicated 7.

Common pitfalls to avoid:

• Overlooking psychological causes (depression and anxiety) leads to inadequate treatment 1
• Ignoring medication side effects can perpetuate fatigue 1
• Missing sleep disorders results in incomplete management 1
• Pursuing extensive investigations without specific clinical findings wastes resources, as serious disease is rare 2