Diagnostic Testing for Patients with Unknown Symptoms
Without specific clinical context, a systematic first-tier laboratory evaluation should include complete blood count, comprehensive metabolic panel (including electrolytes, calcium, magnesium, creatinine), urinalysis, and thyroid function tests, as these provide broad screening for common pathologies while guiding further targeted investigation based on abnormalities detected. 1, 2
Initial Laboratory Panel
The foundation of evaluation for undifferentiated symptoms requires:
Complete blood count (CBC) to detect cytopenias, thrombocytopenia, anemia, or leukocytosis that may indicate hematologic disorders, infection, or systemic disease 1, 2, 3
Comprehensive metabolic panel including sodium, potassium, calcium, magnesium, creatinine, and glucose to assess renal function, electrolyte disturbances, and metabolic derangements 1, 2
Liver function tests to evaluate hepatic pathology that may present with nonspecific symptoms 1
Thyroid-stimulating hormone (TSH) as thyroid dysfunction commonly presents with vague, systemic symptoms and is readily treatable 1, 2
Urinalysis to screen for renal disease, infection, or metabolic abnormalities 1, 4
Additional First-Tier Considerations
Depending on the clinical presentation, consider:
Hemoglobin A1c and fasting glucose if symptoms suggest metabolic dysfunction or diabetes risk factors are present 1, 2
Inflammatory markers (C-reactive protein, procalcitonin) if infection or inflammatory process is suspected 1
Lipid profile as dyslipidemia can be associated with various systemic conditions 2
Algorithmic Approach to Abnormal Results
When CBC abnormalities are detected, pursue targeted evaluation:
- Anemia requires assessment of iron studies, B12, folate, and reticulocyte count to differentiate causes 3
- Leukocytosis or leukopenia necessitates peripheral smear review and consideration of infectious, inflammatory, or hematologic malignancy 3
- Thrombocytopenia or thrombocytosis requires evaluation for underlying causes including bone marrow disorders 3
When metabolic panel abnormalities are detected:
- Renal dysfunction (elevated creatinine) requires assessment of chronicity and potential causes 1
- Electrolyte disturbances guide evaluation for endocrine, renal, or medication-related causes 1
- Hyperglycemia prompts diabetes evaluation with A1c and consideration of complications 1, 2
When urinalysis is abnormal:
- Proteinuria requires quantification and evaluation for renal disease 1, 4
- Hematuria necessitates differentiation between glomerular and non-glomerular sources 4
- Positive leukocyte esterase/nitrite suggests urinary tract infection 4, 5
Critical Pitfalls to Avoid
Do not order extensive imaging or specialized testing without first completing basic laboratory evaluation, as this approach is neither cost-effective nor diagnostically efficient 1
Avoid interpreting isolated laboratory values without clinical context, as many abnormalities require correlation with symptoms and physical findings 3, 6, 7
Do not neglect to repeat borderline or mildly abnormal results, as transient abnormalities are common and may not represent true pathology 3, 7
Recognize that completely normal basic laboratory testing significantly reduces the likelihood of serious underlying pathology and should prompt consideration of functional or non-organic causes 1
When to Pursue Advanced Testing
If initial laboratory evaluation is unrevealing but clinical suspicion remains high:
Natriuretic peptides (BNP/NT-proBNP) if cardiac dysfunction is suspected despite normal initial workup 1
Whole exome sequencing may be considered for complex presentations suggesting genetic or mitochondrial disorders after basic evaluation 1, 2
Targeted imaging (CT, MRI, echocardiography) should be guided by specific clinical findings or laboratory abnormalities rather than ordered empirically 1