What is the proper procedure for conducting a cortisol saliva test for suspected Addison's disease?

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Procedure for Conducting Cortisol Saliva Test for Addison's Disease

For monitoring hydrocortisone replacement therapy in Addison's disease, a salivary cortisol day curve test is recommended, collecting samples before and at 2,4, and 6 hours following the morning dose of hydrocortisone. 1

Test Purpose and Rationale

Salivary cortisol testing provides several advantages for monitoring glucocorticoid replacement therapy in Addison's disease:

  • Practical and reliable method to assess cortisol levels throughout the day 2
  • Non-invasive alternative to serum cortisol measurements
  • Helps identify under- or over-replacement with hydrocortisone
  • Can detect abnormal cortisol patterns that may contribute to symptoms

Collection Procedure

  1. Timing of collection:

    • First sample: Immediately before taking morning hydrocortisone dose
    • Subsequent samples: At 2,4, and 6 hours after the morning dose 1
    • For comprehensive assessment: Consider collecting samples from 8:00 am until midnight at regular intervals 3
  2. Collection method:

    • Use passive drool technique (not cotton swabs) 4
    • Patient should not eat, drink, smoke, or brush teeth for 30 minutes before collection
    • Rinse mouth with water 10 minutes before collection
    • Collect 1-2 mL of saliva in sterile containers
  3. Sample handling:

    • Label each container with patient name, date, time, and relationship to medication dose
    • Refrigerate samples immediately after collection
    • Transport to laboratory within 24 hours or freeze if longer delay expected

Interpretation of Results

  • Compare patient's cortisol curve to normal reference ranges
  • Evaluate for:
    • Peak cortisol levels (Cmax)
    • Time to reach peak levels
    • Overall cortisol exposure (area under the curve)
    • Trough levels before next dose

Clinical Applications

Salivary cortisol day curves can help identify:

  • Overreplacement: Particularly common in the afternoon and evening, which may contribute to sleep disturbances 3
  • Underreplacement: Insufficient cortisol levels that may cause fatigue, weakness, or risk of adrenal crisis
  • Abnormal absorption patterns: Some patients show rapid disappearance of cortisol requiring more frequent dosing 1

Limitations and Considerations

  • Some studies question the utility of salivary cortisol for monitoring hydrocortisone replacement, finding that levels don't consistently correlate with hydrocortisone doses 5
  • Morning salivary cortisol has good sensitivity for diagnosing Addison's disease but may be less useful for ongoing monitoring 6
  • Salivary cortisone levels may be substantially lower in Addison's patients compared to healthy controls 5

Adjusting Treatment Based on Results

If abnormal patterns are detected:

  1. For overreplacement (especially in evening): Consider reducing evening dose to improve sleep quality 3
  2. For underreplacement: Consider increasing total daily dose or redistributing existing dose
  3. For rapid cortisol disappearance: Consider more frequent dosing throughout the day 1

Follow-up

After adjusting glucocorticoid replacement therapy based on salivary cortisol results:

  • Repeat salivary cortisol day curve after 4 weeks to assess the effect of treatment changes 3
  • Monitor for improvement in quality of life, particularly regarding sleep disturbances and fatigue

Remember that the goal of treatment is to mimic normal physiological cortisol patterns as closely as possible while minimizing side effects of both over- and under-replacement.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Salivary cortisol day curves in Addison's disease in patients on hydrocortisone replacement.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2013

Research

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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