What are the steps for a diagnostic examination test?

Diagnostic Examination Test: A Structured Approach

The diagnostic examination process follows a systematic four-step algorithm: initial clinical assessment with history and physical examination, followed by basic laboratory and imaging studies, then specialized testing based on clinical suspicion, and finally disease-specific confirmatory tests. 1

Step 1: Initial Clinical Assessment

History Taking

• Obtain a comprehensive three-generation family history with pedigree analysis to identify hereditary conditions and familial disease patterns 1
• Document all presenting symptoms with specific attention to onset, duration, aggravating and relieving factors, and associated symptoms 1
• Record complete past medical history including prenatal complications, perinatal problems, feeding patterns, growth history, and previous diagnoses 1
• Review all medications, exposures, and environmental factors 1
• The history alone leads to the correct diagnosis in approximately 76% of cases, making it the most powerful diagnostic tool 2

Physical Examination

• Perform a complete physical examination with particular attention to organ systems suggested by the presenting complaint 1, 3
• Assess vital signs including pulse, blood pressure, temperature, and weight 4
• Examine for dysmorphic features, unusual facial characteristics, or visceral anomalies that may suggest specific genetic conditions 1
• Document spleen and liver size when evaluating systemic conditions 1
• The physical examination increases diagnostic confidence and leads to diagnosis in an additional 12% of cases 2

Step 2: Basic Diagnostic Testing

Essential Laboratory Studies

• Order a complete blood count (CBC) with differential to evaluate for cytopenias, abnormal cell populations, lymphocytosis, or eosinophilia 5
• Obtain a comprehensive metabolic panel including liver and renal function tests 1, 5
• Measure lactate dehydrogenase (LDH) and sodium levels as markers for tissue damage or malignancy 1, 5
• Review state-mandated newborn screening results when applicable, as normal results exclude many disorders and avoid unnecessary testing 1

Initial Imaging

• Obtain a 12-lead resting electrocardiogram (ECG) as part of the baseline cardiovascular assessment 1
• Perform chest X-ray when respiratory or thoracic pathology is suspected 1
• Consider echocardiography at rest to rule out left ventricular dysfunction and valvular heart disease 1

Step 3: Targeted Diagnostic Testing Based on Clinical Suspicion

When Specific Diagnosis is Suspected

• If a specific syndrome or condition is suspected based on history and physical examination, proceed directly to targeted testing rather than broad screening 1
• Order disease-specific confirmatory tests (e.g., genetic testing for suspected hereditary conditions, specific antibody panels for autoimmune diseases) 1

When No Specific Diagnosis is Suspected

• Proceed with first-tier broad screening tests appropriate to the clinical presentation 1
• For unexplained developmental delays: chromosomal microarray analysis (CMA) and Fragile X testing 1
• For suspected malignancy: imaging studies (CT scan of chest, abdomen, and pelvis with contrast) to document extent of disease 5
• For peripheral neuropathy: fasting blood glucose/hemoglobin A1c, serum B12 with metabolites, and serum protein immunofixation electrophoresis 6

Specialized Testing

• Order electrodiagnostic studies (nerve conduction studies and electromyography) when neuromuscular disorders are suspected 6
• Perform bone marrow aspiration and biopsy with immunohistochemistry when abnormal cells are found in peripheral blood or myeloproliferative/lymphoproliferative disorder is suspected 1, 5
• Obtain cytogenetics through chromosome banding analysis (CBA) of bone marrow cells when hematologic malignancy is suspected 1

Step 4: Advanced and Confirmatory Testing

Second-Tier Testing

• If first-tier tests are non-diagnostic, consider exome sequencing (ES) or whole genome sequencing (WGS) for unexplained developmental delays, intellectual disability, or congenital anomalies 1
• Perform molecular sequencing and mutation analysis when specific genetic disorders are suspected 1
• Order flow cytometry of peripheral blood for immunophenotyping if lymphoproliferative disorder is suspected 5

Functional and Provocative Testing

• Use provocation testing to confirm diagnosis of chronic inducible conditions and assess trigger thresholds 1
• Perform specialized functional testing based on the organ system involved (e.g., pulmonary function testing for respiratory symptoms) 1

Critical Principles for Test Selection

Pre-Test Probability Considerations

• When pre-test probability of disease is high, select tests with high specificity to confirm the diagnostic suspicion 7
• When pre-test probability of disease is low, choose tests with high sensitivity to exclude the hypothetical disease 7
• Laboratory investigation increases physician confidence in diagnosis from 8.2 to 9.3 on a 10-point scale but leads to the final diagnosis in only 11% of cases 2

Avoiding Common Pitfalls

• Do not order screening tests without diagnostic suspicion, as physiologic and laboratory variation are the most frequent causes of abnormal results in healthy patients 8
• Avoid delaying bone marrow evaluation in patients with concerning peripheral blood findings 5
• Do not overlook the need for HIV testing in patients with unexplained lymphadenopathy 5
• Never dismiss normal vital signs as excluding significant disease—physical examination may be unremarkable even with serious pathology 4

Cost-Effective Testing Strategy

• Base test selection on information obtained from history and physical examination rather than ordering broad screening panels 3, 7
• This approach protects patients from risks of unnecessary testing and is cost-effective 3
• In the absence of signs or symptoms correlating with abnormal screening test results, follow-up testing is usually unnecessary 8