Does taking oral hydrocortisone (cortisol) affect fasting serum cortisol levels?

Impact of Oral Hydrocortisone on AM Fasting Serum Cortisol Levels

Yes, taking oral hydrocortisone will significantly suppress morning fasting serum cortisol levels, as exogenous hydrocortisone administration leads to feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. 1

Mechanism of Suppression

Oral hydrocortisone administration affects serum cortisol measurements through several mechanisms:

1. Direct contribution: Exogenous hydrocortisone (which is identical to cortisol) directly contributes to measured serum cortisol levels
2. HPA axis suppression: Exogenous hydrocortisone inhibits hypothalamic CRH and pituitary ACTH secretion through negative feedback
3. Circadian disruption: Natural cortisol circadian rhythm (with morning peak) is disrupted by exogenous administration

Timing Considerations

The impact on morning cortisol levels depends on dosing schedule:

• Standard hydrocortisone replacement typically involves 15-25 mg total daily dose divided into 2-3 doses 1
• Morning doses taken upon awakening will directly elevate measured cortisol levels
• Evening doses will suppress the natural overnight ACTH rise that normally stimulates morning cortisol production

Clinical Implications

This interference has important implications for cortisol testing:

• Diagnostic testing: AM cortisol measurements for diagnosing adrenal disorders will be invalid in patients taking hydrocortisone
• Monitoring therapy: Morning cortisol levels cannot be used to adjust hydrocortisone replacement doses in patients with adrenal insufficiency 1
• Dexamethasone suppression tests: These will be uninterpretable in patients taking hydrocortisone 1

Recommendations for Accurate Testing

When accurate cortisol measurement is needed:

• Hold hydrocortisone: Temporarily discontinue hydrocortisone before testing (timing depends on specific test)
• Alternative testing: Consider late-night salivary cortisol or 24-hour urinary free cortisol when appropriate 1
• Timing adjustment: If hydrocortisone must be continued, collect samples at trough levels (just before next dose)

Special Situations

Adrenal Insufficiency Monitoring

For patients with adrenal insufficiency on replacement therapy:

• Clinical assessment rather than cortisol levels should guide dose adjustments 1
• Signs of over-replacement: weight gain, insomnia, peripheral edema
• Signs of under-replacement: lethargy, nausea, poor appetite, weight loss, increased pigmentation

Cushing's Syndrome Evaluation

For patients being evaluated for Cushing's syndrome:

• Hydrocortisone must be discontinued before testing
• Late-night salivary cortisol may be preferred as it has higher specificity 1

Practical Considerations

The magnitude of suppression varies based on:

• Hydrocortisone dose (higher doses cause greater suppression)
• Timing of last dose relative to blood sampling
• Individual variations in hydrocortisone metabolism
• Duration of hydrocortisone therapy (longer use leads to more profound HPA axis suppression)

Conclusion

Morning serum cortisol measurements are significantly affected by oral hydrocortisone administration and should not be used for diagnostic purposes or dose adjustment without careful consideration of timing and interpretation. Clinical assessment remains the primary method for monitoring adequacy of hydrocortisone replacement therapy in patients with adrenal insufficiency.