What tests can be done to confirm a diagnosis?

Diagnostic Tests for Confirming a Diagnosis

The most appropriate diagnostic tests to confirm a diagnosis depend on the specific condition being evaluated, with first-tier testing typically including condition-specific laboratory tests, imaging studies, and specialized examinations based on clinical presentation. 1

General Diagnostic Approach

• The diagnostic process should begin with targeted history and physical examination to guide selection of appropriate tests 1
• Diagnostic tests should be selected based on their sensitivity, specificity, and predictive values for the suspected condition 2, 3
• For most conditions, a combination of tests rather than a single test provides the highest diagnostic accuracy 4, 5

Condition-Specific Diagnostic Tests

Neurodevelopmental Disorders

• For suspected developmental delay, autism spectrum disorder (ASD), or intellectual disability:
  • Chromosomal microarray (CMA) is recommended as a first-tier test 1
  • Fragile X testing is recommended as a first-tier test, especially in males 1
  • Exome sequencing (ES) or whole genome sequencing (WGS) should be considered as first- or second-tier tests for unexplained developmental delay, intellectual disability, or congenital anomalies 1
  • MECP2 sequencing should be considered for females with suspected ASD 1

Diabetes

• Diagnosis requires one of the following criteria:
  • Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting 1
  • 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test 1
  • HbA1c ≥6.5% (48 mmol/mol) using a standardized assay 1
  • Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia 1
• Confirmation requires two abnormal test results from the same sample or in two separate test samples 1

Small-Cell Lung Cancer

• Diagnostic workup should include:
  • Chest X-ray and CT scan of chest and upper abdomen 1
  • Complete blood count, liver and renal function tests, LDH, and sodium levels 1
  • For limited disease staging: bone scintigraphy, brain CT/MRI, and bone marrow biopsy when clinically indicated 1

Duchenne Muscular Dystrophy

• Genetic testing for dystrophin mutations is the gold standard:
  • Multiplex ligation-dependent probe amplification or PCR to detect deletions/duplications 1
  • Gene sequencing if deletion/duplication testing is negative 1
• Muscle biopsy with immunocytochemistry and immunoblotting for dystrophin can confirm diagnosis when genetic testing is inconclusive 1

Oral Ulceration

• For difficult-to-diagnose oral ulcers (especially those persisting >2 weeks):
  • Blood tests including complete blood count, coagulation studies, fasting glucose, HIV antibody, and syphilis serology 1
  • Biopsy with histopathological examination is essential for persistent or atypical ulcers 1
  • Additional specialized testing (immunofluorescence, immunohistochemistry) based on initial findings 1

Dry Eye Disease

• Diagnosis requires:
  • At least one positive symptomatic test (OSDI or DEQ-5) 1
  • At least one positive diagnostic test: tear break-up time ≤5 seconds, non-invasive tear break-up time ≤10 seconds, or positive corneal fluorescein staining 1
  • Schirmer's test without anesthesia (≤5 mm/5 min indicates aqueous deficiency) 1
  • Meibomian gland dysfunction examination to classify the subtype 1

Asymptomatic Microhematuria

• Defined as ≥3 RBCs per high-powered field on properly collected urine specimen 1
• Diagnosis requires microscopic confirmation, not just positive dipstick 1
• Urine culture to rule out infection 1
• Renal function assessment (eGFR, creatinine, BUN) 1
• Urologic evaluation with appropriate imaging when benign causes are ruled out 1

Common Pitfalls in Diagnostic Testing

• Relying solely on a single test rather than considering multiple complementary tests 2, 4
• Failing to confirm positive screening test results with more specific diagnostic tests 5
• Not considering the prevalence of the condition when interpreting test results (false positives are more common when prevalence is low) 3, 5
• Overlooking the need for repeat testing to confirm diagnoses in conditions with variable presentation 1
• Using tests without considering their sensitivity and specificity for the specific population being tested 1, 6

Algorithmic Approach to Diagnosis

1. Identify the suspected condition based on presenting symptoms and risk factors
2. Select first-tier tests with highest sensitivity for the suspected condition
3. If first-tier tests are negative but clinical suspicion remains high, proceed to second-tier tests
4. For conditions requiring definitive confirmation, use gold standard tests (e.g., genetic testing, biopsy)
5. When multiple conditions are in the differential diagnosis, select tests that can differentiate between the most likely conditions 4