Which diagnostic test is appropriate for my condition?

Diagnostic Testing Approach: General Framework

The appropriate diagnostic test depends entirely on your specific clinical condition, but the fundamental principle is to select tests based on pre-test probability of disease, with high-sensitivity tests to rule out disease when probability is low, and high-specificity tests to confirm disease when probability is high. 1

Core Diagnostic Strategy

Pre-Test Probability Assessment

• When pre-test probability is LOW: Choose tests with high sensitivity to effectively rule out the suspected disease 1
• When pre-test probability is HIGH: Choose tests with high specificity to confirm your diagnostic suspicion 1
• Clinical information should always accompany test interpretation, as this improves diagnostic accuracy without reducing specificity in most cases 2

Essential Initial Workup Components

Regardless of the specific condition suspected, certain baseline tests provide critical information:

• Complete blood count (CBC) to evaluate for infectious, inflammatory, or hematologic abnormalities 3, 4
• Comprehensive metabolic panel including electrolytes, kidney function (creatinine with estimated GFR), liver function tests (bilirubin, AST, ALT, GGTP), and glucose 3, 4
• 12-lead ECG when cardiovascular involvement is possible, as it provides rhythm, rate, and structural information essential for treatment planning 3

Condition-Specific Diagnostic Pathways

For Suspected Cardiac Disease

Start with non-invasive functional imaging or coronary CT angiography (CCTA) when pre-test probability exceeds 5%. 3

• CCTA is preferred for ruling out obstructive coronary artery disease when pre-test probability is low to moderate (5-50%) 3
• Functional imaging (stress echocardiography, SPECT, PET, or cardiac MRI) is recommended when CCTA shows disease of uncertain significance or when pre-test probability is moderate to high 3
• Invasive coronary angiography is reserved for very high pre-test probability (>85%), severe refractory symptoms, or when non-invasive testing is inconclusive 3
• Natriuretic peptides should be considered in the initial assessment 3

For Suspected Endocrine Disorders (Cushing's Syndrome Example)

Begin with dexamethasone suppression test (DST), 24-hour urinary free cortisol (UFC), and/or late-night salivary cortisol (LNSC), selecting based on patient characteristics and local availability. 3

• Multiple tests are essential: Obtain 2-3 collections of UFC or 2-3 LNSC measurements to account for variability 3
• DST is preferred for shift workers or those with disrupted circadian rhythms, but avoid in women on oral estrogen 3
• LNSC is preferred when renal impairment exists (CrCl <60 mL/min) or significant polyuria is present 3
• Measure dexamethasone levels if false-positive DST is suspected 3
• Never use bilateral inferior petrosal sinus sampling (IPSS) to diagnose hypercortisolism, as it cannot distinguish between healthy controls, pseudo-Cushing's, and true disease 3

For Suspected Gastrointestinal Disorders (IBS Example)

Diagnosis is primarily clinical based on Rome criteria, with selective testing to exclude organic disease. 3

• Screening tests recommended: Stool hemoccult and complete blood count 3
• Additional tests based on symptoms:
  • Sedimentation rate (particularly in younger patients), serum chemistries, albumin 3
  • Stool for ova and parasites based on geographic area and symptom pattern 3
• Colonoscopy is mandatory for patients over age 50 due to higher colon cancer risk 3
• In younger patients: Sigmoidoscopy or colonoscopy only if clinical features suggest disease (diarrhea, weight loss) 3
• For diarrhea-predominant symptoms: Consider lactose breath test, celiac serologies, or small bowel/colonic biopsies for microscopic colitis 3

For Suspected Neurological Disorders (ALS Example)

Electromyography (EMG) and nerve conduction velocity (NCV) studies are mandatory to detect lower motor neuron degeneration and distinguish ALS from mimics. 4

• Brain MRI without IV contrast is the primary imaging modality to exclude structural lesions, tumors, and inflammatory conditions 4
• Comprehensive laboratory exclusion panel:
  • CBC, comprehensive metabolic panel 4
  • Thyroid function tests (TSH, free T4) 4
  • Vitamin B12, folate, and vitamin E levels 4
  • Serum protein electrophoresis 4
  • Anti-ganglioside antibodies (GM1, GD1a, GD1b) to exclude multifocal motor neuropathy 4
  • Anti-acetylcholine receptor and anti-MuSK antibodies to rule out myasthenia gravis 4
• CSF examination to exclude inflammatory/infectious mimics, including cell count, protein, glucose, IgG index, oligoclonal bands, and cytology 4
• Genetic testing for ALS-associated genes (C9orf72, SOD1, FUS, TARDBP) when family history exists 4

For Suspected Metabolic Disorders (Mitochondrial Cytopathy Example)

Whole exome sequencing should be considered as a first or second-tier test when clinical presentation is complex. 5

• Initial laboratory panel:
  • CBC to detect cytopenias or thrombocytopenia 5
  • Basic metabolic panel including calcium, magnesium, creatinine 5
  • Fasting glucose and HbA1c 5
  • Thyroid function tests (TSH) 5
  • Lipid profile 5

For Suspected Renal Osteodystrophy

Intact plasma PTH levels are the primary biochemical marker to distinguish high- from low-turnover bone disease, though bone biopsy remains the gold standard. 3

• Bone biopsy with double tetracycline labeling is indicated for:
  • Pathological fractures 3
  • PTH levels 100-500 pg/mL with unexplained hypercalcemia, severe bone pain, or elevated bone alkaline phosphatase 3
  • Suspected aluminum bone disease 3
• Bone radiographs are NOT indicated for assessing bone disease of CKD, though useful for detecting vascular calcification 3
• DEXA scanning should be performed in patients with fractures or known osteoporosis risk factors 3

Critical Pitfalls to Avoid

• Never rely solely on clinical examination when objective testing is available, as up to 10% of initial diagnoses may represent mimic disorders 4
• Do not skip comprehensive laboratory panels even when a specific diagnosis seems obvious, as treatable conditions frequently present identically 4
• Avoid using standard reference ranges without considering disease-specific normative data, which can lead to misinterpretation 5
• Do not delay appropriate testing in an attempt to be conservative; early accurate diagnosis prevents complications and improves outcomes 3, 4
• Ensure adequate sample collection information is available before ordering tests, including whether serum or plasma is needed, required volume, and storage conditions 6

Test Interpretation Principles

• Always interpret tests with clinical context, as this improves accuracy without sacrificing specificity 2
• Repeat abnormal screening tests to confirm findings before proceeding to invasive or expensive confirmatory testing 3
• Use multiple complementary tests rather than relying on a single result when diagnosis remains uncertain 3
• Consider test limitations based on patient characteristics (renal function, medications, circadian rhythm disruption) when selecting diagnostic modalities 3