Assessing and Investigating Patients with Persistent Tiredness Comprehensive History Taking Characterize the Fatigue Onset: Gradual vs. sudden. Duration: Acute (<1 month), subacute (1-3 months), chronic (>3 months). Pattern: Continuous or intermittent, morning or evening predominance. Severity: Impact on daily activities and quality of life. Associated Symptoms Sleep disturbances: Insomnia, sleep apnea, restless legs syndrome. Mental health: Depression, anxiety, stress. Physical symptoms: Weight loss, fever, pain, dyspnea. Medical History Chronic diseases: Diabetes, hypothyroidism, heart failure, COPD. Recent infections: Viral illnesses, post-viral fatigue syndrome. Medication review: Side effects, drug interactions, sedatives, beta-blockers. Surgical history: Particularly recent surgeries, anesthesia effects. Lifestyle Factors Diet and hydration: Nutritional deficiencies, dehydration. Exercise habits: Over-exercise or sedentary lifestyle. Substance use: Alcohol, caffeine, illicit drugs. Work and stress: Occupational hazards, burnout, sleep deprivation. Family History Genetic predispositions: Thyroid disorders, autoimmune diseases, mental health conditions. Physical Examination General Appearance Signs of chronic illness, weight changes, pallor, jaundice. Vital Signs Blood pressure, heart rate, respiratory rate, temperature. Head and Neck Examination Thyroid enlargement, lymphadenopathy, oral and pharyngeal health. Cardiovascular System Heart sounds, murmurs, signs of heart failure (jugular venous distension, peripheral edema). Respiratory System Breath sounds, signs of respiratory distress, oxygen saturation. Abdominal Examination Hepatosplenomegaly, masses, tenderness. Neurological Examination Muscle strength, reflexes, sensory examination, signs of neuropathy. Musculoskeletal Examination Joint swelling, tenderness, range of motion. Laboratory Investigations Basic Blood Tests Complete Blood Count (CBC): Anemia, infection, chronic disease indicators. Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Inflammation markers. Thyroid Function Tests (TFTs): TSH, Free T4, Free T3. Metabolic Panel Electrolytes: Sodium, potassium, calcium. Renal function: Urea, creatinine. Liver function: ALT, AST, ALP, bilirubin. Glucose levels: Fasting glucose, HbA1c. Vitamin and Mineral Levels Vitamin D: Common deficiency associated with fatigue. Vitamin B12 and Folate: Important for hematologic and neurologic health. Iron studies: Ferritin, serum iron, transferrin saturation. Hormonal Studies Adrenal function: Cortisol levels, ACTH stimulation test. Sex hormones: Testosterone, estrogen, progesterone levels where appropriate. Infection Screening Viral serologies: HIV, Hepatitis B and C, Epstein-Barr virus (EBV). Tuberculosis screening: TB skin test or IGRA. Autoimmune Panel ANA, Rheumatoid Factor (RF): Screening for systemic autoimmune diseases. Specific antibodies: Anti-TPO (thyroid), Anti-CCP (rheumatoid arthritis). Imaging and Specialized Tests Chest X-ray Evaluates for infections, chronic lung diseases, cardiac enlargement. Echocardiogram Assesses cardiac function, valvular diseases, ejection fraction. Abdominal Ultrasound Liver, spleen, kidneys, abdominal masses. Polysomnography Sleep study: Identifies sleep apnea, periodic limb movements, insomnia disorders. ECG and Holter Monitoring Identifies arrhythmias, ischemic changes, continuous monitoring for episodic symptoms. MRI or CT Scan Brain imaging: When neurological symptoms are present, for structural abnormalities. Abdominal/pelvic imaging: For suspected internal masses or organ dysfunction. Differential Diagnoses Endocrine Disorders Hypothyroidism: Weight gain, cold intolerance, constipation, dry skin. Diabetes mellitus: Polyuria, polydipsia, polyphagia, recurrent infections. Adrenal insufficiency: Hyperpigmentation, hypotension, salt craving. Hematological Disorders Anemia: Iron-deficiency, pernicious anemia, hemolytic anemia. Chronic diseases: Anemia of chronic disease, thalassemias, hemoglobinopathies. Infectious Diseases Chronic infections: Tuberculosis, HIV, hepatitis, endocarditis. Post-infectious syndromes: Post-viral fatigue, chronic Lyme disease. Cardiovascular Disorders Heart failure: Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema. Chronic obstructive pulmonary disease (COPD): Cough, sputum production, wheezing. Renal and Hepatic Disorders Chronic kidney disease: Uremia, fluid retention, electrolyte imbalances. Liver disease: Jaundice, ascites, varices, hepatic encephalopathy. Autoimmune and Inflammatory Conditions systemic lupus erythematosus (SLE): Malar rash, photosensitivity, arthritis. Rheumatoid arthritis: Symmetrical joint pain, morning stiffness, nodules. Sarcoidosis: Pulmonary involvement, skin lesions, hypercalcemia. Psychiatric and Neurological Conditions Depression: Low mood, anhedonia, changes in appetite and sleep. Anxiety disorders: Excessive worry, palpitations, tremors. Chronic fatigue syndrome (CFS): Profound fatigue, post-exertional malaise, cognitive dysfunction. Management and Follow-up Lifestyle Modifications Diet: Balanced nutrition, adequate caloric intake, hydration. Exercise: Tailored to patient’s capacity, gradual increase in activity. Sleep hygiene: Regular sleep schedule, minimize disturbances, create a restful environment. Stress management: Mindfulness, relaxation techniques, counseling. Medical Interventions Medications: Treat underlying conditions (e.g., thyroid hormone replacement, antidepressants). Supplements: Iron, vitamin B12, vitamin D as needed based on deficiencies. Pain management: Analgesics, physical therapy for musculoskeletal issues. Monitoring and Reassessment Regular follow-ups: Track progress, adjust treatment plans, address new symptoms. Repeat investigations: As needed based on initial findings and ongoing symptoms. Referral to specialists: Endocrinologist, hematologist, infectious disease specialist, psychiatrist. Patient Education and Support Inform about condition: Pathophysiology, expected course, treatment options. Support groups: Connect with others experiencing similar issues, emotional support. Multidisciplinary approach: Collaboration between primary care, specialists, allied health professionals. Red Flags and Urgent Referrals Severe, unexplained weight loss Possible malignancy, severe chronic disease. Significant anemia Hemoglobin <7 g/dL, symptomatic anemia, need for transfusion. Severe, persistent pain Possible malignancy, severe musculoskeletal or neuropathic pain. New-onset neurological deficits Possible central nervous system pathology, stroke, multiple sclerosis. Severe psychiatric symptoms Suicidal ideation, severe depression, psychosis. By following a systematic and thorough approach to the assessment and investigation of patients presenting with persistent tiredness, clinicians can uncover underlying conditions, provide targeted treatments, and improve patient outcomes. This process not only addresses the symptom of fatigue but also enhances the overall health and well-being of the patient.