Morning Cortisol and ACTH Testing: Fasting Requirements
Direct Answer
Morning cortisol and ACTH testing does NOT require fasting. 1
Optimal Timing Requirements
The critical requirement for morning cortisol and ACTH testing is timing, not fasting status:
- Both tests must be drawn between 8:00-9:00 AM to capture the physiologic peak of cortisol secretion that occurs in early morning hours, which is essential for accurate interpretation of adrenocortical function 1
- The 8:00-9:00 AM window provides optimal sensitivity (68%) and specificity (100%) for detecting ACTH-dependent hypercortisolism when evaluating Cushing's disease 1
- This timing is the standard reference point used in all diagnostic algorithms for both adrenal insufficiency and Cushing's syndrome evaluation 1
Why Fasting Is Not Required
The physiologic rationale for morning timing relates to circadian cortisol rhythm, not metabolic state:
- Cortisol follows a diurnal rhythm with highest levels in the morning and lowest at midnight, making morning testing the standard reference point regardless of food intake 2
- The ACTH stimulation test has been shown to be robust for most test-condition-related factors, including fasting versus nonfasting status 3
- In a study of 100 subjects, multivariate analysis found that 30-minute cortisol response was predicted by baseline cortisol and central adiposity, but not by fasting/nonfasting status 3
Critical Testing Requirements
When drawing morning ACTH and cortisol together, these requirements are mandatory:
- Both must be drawn simultaneously at 8:00-9:00 AM from the same blood draw, which is essential for distinguishing primary from secondary adrenal insufficiency 1
- ACTH is extremely labile and requires immediate processing on ice, so coordinate with the laboratory before drawing to ensure proper handling 1
- The patient should avoid strenuous exercise for 24-48 hours before testing, as recent physical or mental stress significantly elevates cortisol 1
Important Clinical Caveats
Several factors can invalidate morning cortisol testing regardless of fasting status:
- Shift workers and patients with disrupted circadian rhythms should not have AM cortisol testing, as their cortisol peaks occur at different times and will yield unreliable results 1
- Medications affecting cortisol binding globulin (CBG) must be documented, including oral estrogens, pregnancy status, and chronic active hepatitis, as these increase total cortisol levels and can lead to false interpretation 1
- Oral contraceptives severely affect both total cortisol and calculated free cortisol, with OC users showing 2-fold elevated 30-minute cortisol but lowered calculated free cortisol compared to unmedicated subjects, making the test unreliable unless OC has been discontinued 3
Practical Implementation
For optimal test accuracy, ensure:
- Blood draw occurs between 8:00-9:00 AM (not earlier, not later) 1
- Patient has been awake and upright for at least 30 minutes before the draw 2
- ACTH sample is immediately placed on ice and processed urgently 1
- Document all medications, particularly oral contraceptives, estrogens, and CYP3A4 inducers 1, 3
- No fasting is required—patients may eat breakfast before the test 3