ACTH Levels and Circadian Rhythm
No, ACTH is at its HIGHEST level in the morning, not its lowest. ACTH follows a distinct circadian rhythm with peak levels occurring in the early morning hours (around 6-9 AM) and reaching its nadir (lowest point) at midnight 1, 2.
Physiological Circadian Pattern
- ACTH and cortisol both follow a circadian rhythm with peak levels in the morning and lowest levels at midnight 1, 3
- The morning peak typically occurs between 6-9 AM, which is why diagnostic guidelines specifically recommend measuring ACTH during this time window for accurate interpretation 1, 2
- This diurnal variation is critical for proper diagnostic evaluation of adrenal and pituitary disorders 3
Clinical Implications for Diagnostic Testing
- Morning (08:00-09:00h) plasma ACTH measurement is the optimal and standard time for initial assessment of pituitary-adrenal function 2
- The established diagnostic cutoffs for ACTH (>5 pg/mL for ACTH-dependent disease, >29 pg/mL for Cushing's disease) are specifically based on morning measurements 2, 4
- Afternoon ACTH measurements are unreliable because levels are physiologically lower and do not correspond to established diagnostic thresholds 2
Diagnostic Context
When evaluating for conditions like Cushing's syndrome or adrenal insufficiency:
- Morning ACTH levels combined with morning cortisol provide the most reliable diagnostic information 1, 2
- In normal individuals, the morning ACTH range (9:00-9:30 AM) is 9-24 ng/L, while patients with Cushing's disease show elevated levels of 39-109 ng/L 5
- The timing is so critical that delayed sleep phase can shift the entire cortisol/ACTH curve by 7-8 hours, potentially causing misinterpretation if not recognized 3
Important Caveat
Spontaneous awakening in the morning triggers an abrupt decline in both ACTH and cortisol levels after a brief initial rise 6. This means that the exact timing of blood draw relative to awakening can affect results, emphasizing why standardized morning collection times (08:00-09:00h) are recommended in guidelines 2.