How should investigations be organized for a patient presenting with non-specific symptoms?

Organizing Investigations for Non-Specific Symptoms

Begin with a targeted history and physical examination to identify specific clinical patterns that guide selective laboratory and imaging studies, rather than ordering routine screening panels in asymptomatic patients. 1, 2

Initial Clinical Assessment

History Taking Priority

• Document the exact symptom characteristics: onset timing, duration, severity, progression, and associated features that may suggest specific organ system involvement 3
• Identify high-risk features requiring urgent investigation: fever, weight loss, night sweats, bleeding, neurological changes, or acute cardiopulmonary symptoms 4, 5
• Obtain three-generation family history when symptoms suggest hereditary conditions, particularly in neurodevelopmental or genetic presentations 4
• Record medication history, occupational exposures, and lifestyle factors (smoking, alcohol) that may explain symptoms or guide risk stratification 4

Physical Examination Focus

• Target examination to symptom-specific findings rather than performing unfocused screening 1, 2
• The history leads to diagnosis in 76% of cases, with physical examination contributing an additional 12%, making these foundational before ordering tests 2

Laboratory Investigation Strategy

Selective Testing Based on Clinical Suspicion

• Order tests only when clinical findings suggest specific diagnoses - routine screening in asymptomatic patients without clinical indicators is not recommended 4
• Complete blood count (CBC) when anemia, infection, or hematologic disorder is suspected based on symptoms like fatigue, pallor, fever, or bleeding 6
  • Assess hemoglobin/hematocrit for anemia or polycythemia 6
  • Use MCV to classify anemia type (microcytic, normocytic, macrocytic) 6
  • Evaluate platelet count when bleeding or clotting concerns exist 6

Avoid Routine Panels Without Indication

• Do not order routine chemistry panels, liver function tests, or complete blood counts in asymptomatic patients without specific clinical findings 4
• Cardiac biomarkers (troponin, CK-MB) should be measured only when acute coronary syndrome is suspected based on chest pain characteristics, ECG changes, or risk factors 4
  • Measure at presentation and 2-6 hours later if initial presentation is within 6 hours of symptom onset 4

Imaging Investigation Approach

Symptom-Directed Imaging Only

• CT scans, MRI, bone scans, and ultrasounds should only be performed when indicated by specific symptoms - not as routine screening 4
• Chest radiography is appropriate when respiratory symptoms, cardiac concerns, or thoracic pathology is suspected clinically 4

Special Population Considerations

• For suspected genetic or neurodevelopmental disorders: Perform comprehensive history and physical first; if specific syndrome suspected, order targeted genetic testing rather than broad panels 4
• Chromosomal microarray (CMA) and Fragile X testing are first-tier genetic tests only when developmental delay, intellectual disability, or autism spectrum disorder is clinically evident 4

Common Pitfalls to Avoid

• Ordering "routine" or "screening" blood work without clinical indication wastes resources and may lead to false positives requiring unnecessary follow-up 4
• Failing to document timing of symptoms relative to test ordering, particularly for time-sensitive markers like cardiac troponins or viral testing 4
• Pursuing incidental findings aggressively without considering clinical context - most incidental findings on imaging do not require intervention 4
• Using outdated markers: Total CK without MB fraction, AST, ALT, or LDH should not be used for cardiac injury detection 4

Investigation Sequence Algorithm

1. Comprehensive history and targeted physical examination generate diagnostic hypotheses 1, 2, 7
2. If specific diagnosis suspected: Order targeted confirmatory tests for that condition 4
3. If no specific diagnosis emerges but symptoms persist: Consider specialist referral before ordering broad screening panels 4
4. Reassess at regular intervals based on symptom severity and patient risk factors, rather than ordering routine follow-up testing in asymptomatic patients 4

The physician's confidence in diagnosis increases from 7.1/10 after history to 8.2/10 after physical examination to 9.3/10 after laboratory investigation, demonstrating that tests confirm rather than generate diagnoses 2