Diagnostic Approach for Patients with Unknown Symptoms
For patients with unknown symptoms, a comprehensive diagnostic workup should include a complete blood count with differential, comprehensive metabolic panel, inflammatory markers, and targeted imaging based on any localizing signs or symptoms. This systematic approach ensures that critical diagnoses are not missed while avoiding unnecessary testing.
Initial Laboratory Evaluation
Basic Laboratory Tests
Complete Blood Count (CBC) with differential 1, 2
- Evaluate for leukocytosis (>14,000 cells/mm³), elevated band count (>1500/mm³), or increased percentage of neutrophils (>90%) which have high likelihood ratios for bacterial infection
- Assess for anemia, thrombocytopenia, or other hematologic abnormalities
Comprehensive Metabolic Panel 1
- Liver function tests: bilirubin, albumin, ALT, ALP, GGT
- Renal function: BUN, creatinine
- Electrolytes: sodium, potassium, chloride, bicarbonate
- Glucose
Inflammatory Markers 1
- C-reactive protein (CRP)
- Procalcitonin (particularly useful in suspected sepsis)
- Erythrocyte sedimentation rate (ESR)
Additional First-Line Tests
- Urinalysis with culture if indicated 1
- Coagulation studies (PT/INR, PTT) 1
- Thyroid function tests (TSH, free T4)
Targeted Diagnostic Testing Based on Clinical Suspicion
Cardiovascular Evaluation
- ECG
- Cardiac biomarkers (troponin, BNP) if cardiac symptoms present
- Echocardiogram for suspected structural heart disease 1
Respiratory Evaluation
- Chest X-ray for respiratory symptoms or fever
- Pulse oximetry
- Sputum culture if productive cough present 1
Gastrointestinal Evaluation
- Stool studies for diarrhea (culture, ova and parasites, C. difficile)
- Abdominal imaging (ultrasound or CT) for abdominal pain 1
- AST:ALT ratio calculation to assess for advanced liver fibrosis 1
Infectious Disease Workup
- Blood cultures (two sets) if fever present 1
- HIV, Hepatitis B and C screening 2
- Specific serologies based on epidemiological risk factors
Advanced Diagnostic Testing
Imaging Studies
- CT scan for focused evaluation based on symptoms
- MRI for neurological symptoms or when soft tissue detail is needed
- PET-CT for suspected occult malignancy or lymphoma 2
Specialized Testing
- Lumbar puncture for suspected CNS infection or inflammation
- Lymph node biopsy for unexplained lymphadenopathy (excisional biopsy preferred over core needle) 2
- Bone marrow biopsy for unexplained cytopenias or suspected hematologic malignancy 2
Common Pitfalls to Avoid
- Ordering non-specific panels without clinical direction - leads to incidental findings and unnecessary follow-up
- Inadequate tissue sampling - fine-needle aspirates are often insufficient for definitive diagnosis of lymphoma 2
- Overlooking basic tests - simple tests like CBC and CMP often provide critical diagnostic clues
- Failure to repeat abnormal tests - confirmation of abnormal results is essential before extensive workup
- Missing pre-analytical errors - improper specimen collection or handling can lead to false results
Special Considerations
- For suspected liver disease, calculate AST:ALT ratio (>1 suggests advanced fibrosis/cirrhosis) 1
- For suspected infection in elderly patients, note that fever may be absent; focus on leukocytosis, band forms, or altered mental status 1
- For suspected ascites, diagnostic paracentesis with ascitic fluid analysis is essential 1
- For suspected lymphoma, excisional lymph node biopsy providing adequate tissue for morphology, immunohistochemistry, flow cytometry, and molecular studies is mandatory 2
This approach balances the need for thorough evaluation while avoiding unnecessary testing, focusing on tests most likely to yield diagnostic information based on the patient's presentation.