Normal ACTH Range in Adults
The normal range for morning (8-9 AM) plasma ACTH in adults is approximately 9-52 pg/mL (2-11 pmol/L), though this varies by assay and must be interpreted in the context of timing and clinical presentation. 1
Reference Ranges by Time of Day
Morning (8:00-9:30 AM) measurements are critical because ACTH follows a circadian rhythm with peak levels in early morning:
- Morning (8-9 AM): 9-52 pg/mL (approximately 2-11 pmol/L) 1, 2
- Midday (10 AM-1 PM): 14-93 pg/mL 3
- Evening (4-10 PM): <10-34 pg/mL 3
The most clinically useful reference range is the 9:00-9:30 AM window, which shows 9-24 ng/L (approximately 9-24 pg/mL) in healthy adults when measured precisely during this timeframe. 2
Critical Context for Interpretation
ACTH values must always be interpreted alongside cortisol levels to determine the appropriateness of the pituitary-adrenal response. 1
In Cushing's Disease (ACTH-dependent hypercortisolism):
- ACTH >5 ng/L (>1.1 pmol/L) with elevated cortisol supports the diagnosis 1
- ACTH >29 ng/L (6.4 pmol/L) has 70% sensitivity and 100% specificity for Cushing's disease 1
- Morning values typically range 39-109 ng/L in confirmed cases 2
In Primary Adrenal Insufficiency:
- ACTH is markedly elevated (often >100 pg/mL) with low cortisol 4, 5
- Cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic 4, 5
In Secondary Adrenal Insufficiency:
- ACTH is low or inappropriately normal (<10 pg/mL) with low cortisol 4
Important Caveats
Assay variability is substantial and clinically significant. Different ACTH assays show considerable inter-laboratory variation, with some achieving <10% coefficient of variation while others consistently exceed 20%. 6 Most critically, assays correctly identify only 60% of patients with truly suppressed ACTH levels, making low-normal values particularly unreliable. 6
Timing precision is non-negotiable. The normal range narrows considerably when samples are drawn precisely between 9:00-9:30 AM (9-24 pg/mL) compared to the broader 8:00 AM-1:00 PM window. 2 Drawing blood even 30-60 minutes outside this window can yield misleadingly low values in healthy individuals.
Never interpret ACTH in isolation. An ACTH value within the reference range may be entirely inappropriate if cortisol is elevated (suggesting autonomous cortisol production) or if cortisol is low (suggesting secondary adrenal insufficiency). 1, 4