Timing of ACTH Stimulation Test
The ACTH stimulation test should be performed in the morning between 8:00-9:00 AM to ensure accurate interpretation of results. 1, 2
Rationale for Morning Testing
- Morning ACTH measurement (08:00-09:00h) is the optimal time for initial assessment, particularly for Cushing's disease evaluation 2
- In patients with confirmed Cushing syndrome, a normal or elevated 09:00h plasma ACTH supports the diagnosis of ACTH dependency and Cushing disease 1
- Using a cut-off value of 29 ng/L (6.4 pmol/L), morning ACTH has 70% sensitivity and 100% specificity for diagnosing Cushing disease in the presence of confirmed hypercortisolism 2
Physiological Considerations
- Cortisol follows a diurnal rhythm with highest levels in the morning and lowest at midnight, making morning testing the standard reference point 1
- Morning testing provides better standardization across patients and allows for comparison with established reference ranges 1
- In healthy subjects, basal and peak serum cortisol levels are significantly higher in the morning compared to afternoon measurements 3
Diagnostic Protocol Recommendations
- For diagnosing Cushing syndrome, guidelines recommend measuring morning (09:00h) plasma ACTH to determine if the condition is ACTH-dependent or ACTH-independent 1
- For adrenal incidentalomas, the 1mg dexamethasone suppression test (DST) should be performed with cortisol measured at 8AM following dexamethasone administration at 11PM the previous night 1
- For patients with suspected adrenal insufficiency, morning ACTH stimulation testing provides more reliable baseline cortisol values 1
Special Considerations
- For patients with cyclical Cushing's disease, hypercortisolemia must be confirmed immediately prior to diagnostic procedures to ensure the patient is in an active disease phase 1
- In patients being evaluated for primary aldosteronism, the aldosterone/renin ratio test should be done in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes 1
- For patients with suspected immune-related adverse events causing adrenal insufficiency, morning ACTH and cortisol levels should be measured for proper diagnosis 1
Potential Pitfalls
- Afternoon testing may lead to false interpretations due to the natural diurnal variation in cortisol levels 3, 4
- Failure to standardize the timing of the test may result in inconsistent results and diagnostic errors 2
- Some studies have suggested that there is no diurnal variation in adrenal response to ACTH when using submaximal doses and when baseline cortisol is suppressed, but morning testing remains the standard practice 4
By performing the ACTH stimulation test in the morning between 8:00-9:00 AM, clinicians can ensure standardized results that align with established diagnostic criteria and reference ranges, leading to more accurate diagnosis and appropriate management of adrenal disorders.