Does pregnancy affect Adrenocorticotropic hormone (ACTH) stimulation test results?

Pregnancy Effects on ACTH Stimulation Test Results

Yes, pregnancy significantly affects ACTH stimulation test results, with progressive increases in both baseline and stimulated cortisol levels throughout pregnancy requiring trimester-specific reference ranges for accurate interpretation.

Physiological Changes in Pregnancy Affecting the HPA Axis

Pregnancy induces several important changes in the hypothalamic-pituitary-adrenal (HPA) axis that directly impact ACTH stimulation test results:

• Increased cortisol binding globulin (CBG): Estrogen-induced elevations in CBG during pregnancy significantly increase total serum cortisol levels 1
• Progressive hypercortisolism: Basal cortisol levels rise throughout pregnancy, reaching levels 2-3 times higher than non-pregnant values by the third trimester 2, 3
• Enhanced adrenal responsiveness: The maternal adrenal glands show progressively increased responsiveness to ACTH stimulation as pregnancy advances 2
• Altered ACTH levels: Despite rising cortisol levels, maternal ACTH levels are actually lower throughout pregnancy compared to non-pregnant women, though they increase progressively from first to third trimester 4, 3

ACTH Stimulation Test Results in Pregnancy

The standard 250-μg ACTH stimulation test shows significant differences in pregnancy:

• Baseline cortisol: Progressively increases during pregnancy trimesters and decreases postpartum 2
• Stimulated cortisol response: Enhanced responsiveness of maternal adrenal glands to ACTH stimulation as pregnancy progresses 2
• Aldosterone response: Both baseline and stimulated aldosterone levels increase significantly throughout pregnancy 2

Clinical Implications for Testing

When performing ACTH stimulation testing in pregnancy:

1. Use trimester-specific reference ranges: Standard non-pregnant cutoffs will lead to false negative results for adrenal insufficiency 2
2. Consider salivary free cortisol: In the setting of pregnancy-induced CBG elevation, salivary free cortisol provides a more consistent, binding-globulin-independent measure of adrenal function than total serum cortisol 2
3. Timing considerations: Estrogen-containing medications can affect results by increasing CBG levels; these should be stopped 4-6 weeks before testing 1
4. Alternative approach: If testing cannot be delayed, concomitant measurement of CBG can help interpret elevated total cortisol levels 1

Important Caveats and Pitfalls

• Misdiagnosis risk: Using non-pregnant reference ranges may lead to missed diagnoses of adrenal insufficiency in pregnant women
• Medication interference: Glucocorticoids and spironolactone may falsely elevate plasma cortisol levels and should be stopped on the day of testing 1
• Diurnal variation: Despite altered HPA axis function, the diurnal variation of cortisol is maintained during pregnancy 3
• Postpartum recovery: The HPA axis is transiently suppressed postpartum (similar to post-cure Cushing's syndrome) and normalizes by approximately 12 weeks 3

Practical Approach to ACTH Testing in Pregnancy

1. Establish trimester-specific cutoffs for both baseline and stimulated cortisol
2. Consider salivary cortisol measurement when available
3. Interpret results cautiously in the context of pregnancy-related hypercortisolism
4. Recognize that adrenal reserve increases as pregnancy progresses, which should be considered when interpreting results 2

The most reliable approach is to use trimester-specific reference ranges and consider salivary free cortisol when available, as it provides a more physiological and less variable measure of adrenal reserve in pregnancy than serum cortisol 2.