Should cortisol levels be measured after fasting or food intake?

Cortisol Level Measurement: Fasting vs. After Food

Cortisol levels should be measured in a fasting state, particularly for morning measurements, as food intake can influence cortisol levels and potentially affect diagnostic accuracy. 1

Optimal Timing and Conditions for Cortisol Measurement

Types of Cortisol Tests

1. Serum Cortisol

   • Morning measurements (8:00-9:00 am) should be collected in a fasting state
   • Represents the peak of normal circadian rhythm
   • Fasting helps standardize results and minimize variability

2. Late Night Salivary Cortisol (LNSC)

   • Collected at bedtime or midnight
   • Food intake should be avoided for 1-2 hours before collection
   • Reflects loss of normal circadian rhythm in Cushing's syndrome 1

3. 24-hour Urinary Free Cortisol (UFC)

   • Food intake during collection is acceptable
   • Measures overall cortisol production over 24 hours
   • Independent of corticosteroid binding globulin changes 1

Impact of Food on Cortisol Levels

Food intake can affect cortisol measurements through several mechanisms:

• Stimulation of cortisol secretion in response to meals
• Evening food intake has more pronounced effects on glucose levels and insulin secretion, which can indirectly affect cortisol levels 2
• Potential cross-reactivity with certain food components in some assays

Standardized Collection Protocols

For Serum Cortisol

• Collect in the morning (8:00-9:00 am) after overnight fasting
• For dexamethasone suppression test, measure serum cortisol at 8:00 am after overnight dexamethasone administration 1
• Avoid strenuous physical activity for at least 24 hours (ideally 48 hours) before collection 1

For Salivary Cortisol

• Avoid food intake for 1-2 hours before collection
• Avoid teeth brushing or oral hygiene products 1-2 hours prior to collection 1
• For late-night measurements, collect at usual bedtime rather than fixed midnight time 1
• Use inert polypropylene or polyethylene collection materials (avoid cotton-based materials which can retain hormones) 1

For 24-hour UFC

• Normal food intake is acceptable during collection
• Collect at least 2-3 separate 24-hour samples to account for intra-patient variability 1
• Consider factors that can influence results: sex, BMI, age, urinary volume, and sodium intake 1

Special Considerations

Diurnal Variation

• Cortisol follows a strong circadian rhythm with highest levels in early morning and lowest at midnight
• The cortisol awakening response can affect morning measurements 3
• For biomarkers affected by diurnal variation, serial sampling across 24-48 hours may be more accurate 1

Factors That Can Affect Results

• Physical and mental stressors increase salivary cortisol levels 1
• Sleep disturbances can decrease morning awakening salivary cortisol in patients with insomnia 1
• Medications can interfere with results (e.g., oral estrogens increase CBG levels) 1
• Acute infections within past 2 weeks can elevate immune and related salivary markers 1

Common Pitfalls to Avoid

1. Ignoring circadian rhythm

   • Collecting samples at inconsistent times can lead to misinterpretation
   • Midnight/bedtime cortisol is crucial for diagnosing Cushing's syndrome

2. Not accounting for pre-analytical variables

   • Physical activity, stress, and food intake can all affect results
   • Standardize collection conditions for accurate interpretation

3. Using inappropriate collection materials

   • Cotton-based materials can retain hormones like cortisol 1
   • Use inert materials for accurate measurement

4. Relying on a single measurement

   • Multiple measurements are recommended due to variability
   • At least 2-3 samples should be collected for UFC and LNSC 1

5. Not considering special populations

   • Different protocols may be needed for children/adolescents 1
   • Night-shift workers require special consideration for LNSC testing 1

By following these standardized protocols and considering the impact of food intake on cortisol levels, clinicians can obtain more accurate and reliable results for diagnosing conditions like Cushing's syndrome and adrenal insufficiency.