What is a normal Adrenocorticotropic hormone (ACTH) level?

Normal ACTH Levels

The normal reference range for plasma ACTH is approximately 10-60 pg/mL when measured in the morning (08:00-09:00h), with values >5 pg/mL considered detectable and values <5 pg/mL suggesting ACTH suppression. 1

Reference Values and Timing

• Morning plasma ACTH levels in healthy individuals typically range from 10-60 pg/mL, with optimal measurement timing at 08:00-09:00h for standardization 1
• More specifically, the 9:00-9:30 AM range in normal subjects is 9-24 ng/L (equivalent to approximately 9-24 pg/mL), showing no overlap with Cushing's disease patients 2
• In normal young adults (25-45 years), basal ACTH levels average 23.1 ± 13.6 pg/mL 3
• In elderly subjects (60-85 years), basal ACTH levels average 17.5 ± 11.2 pg/mL, showing no significant age-related decline 3
• Historical radioimmunoassay data shows normal morning (8-10 AM) ACTH concentrations averaging 22 pg/mL, with evening levels (10-11 PM) dropping to approximately 9.6 pg/mL 4

Critical Context for Interpretation

ACTH must always be interpreted alongside cortisol levels to determine the appropriateness of the pituitary-adrenal response. 1

Physiologic Patterns

• ACTH follows a circadian rhythm with highest levels in the morning and lowest at midnight, making morning testing the standard reference point 1
• The diurnal variation is not always well-marked throughout daytime hours, but ACTH usually falls to its lowest value in late evening 4

Clinical Interpretation Scenarios

• Primary adrenal insufficiency: Low cortisol + elevated ACTH is diagnostic 1
• Secondary adrenal insufficiency: Low cortisol + inappropriately normal or low ACTH indicates pituitary/hypothalamic dysfunction 1
• ACTH-dependent Cushing's syndrome: Elevated cortisol + ACTH >5 pg/mL indicates ACTH-dependent disease 1
• ACTH-independent Cushing's syndrome: ACTH <5 pg/mL or undetectable levels suggest adrenal source of cortisol excess 1

Diagnostic Thresholds for Cushing's Syndrome

• Any ACTH level >5 pg/mL is detectable and suggests ACTH-dependent Cushing's syndrome with high certainty 1, 5
• ACTH >29 pg/mL has 70% sensitivity and 100% specificity for diagnosing Cushing's disease in the presence of confirmed hypercortisolism 1, 5
• In patients with Cushing's disease, ACTH concentrations range from 39-109 ng/L, showing no overlap with the tightly defined 9 AM normal range 2
• In adrenal tumors causing Cushing's syndrome, ACTH levels are nondetectable or low and usually nonstimulatable 6
• In ectopic ACTH secretion, high ACTH levels (mean 0.42 ± 0.07 mU/100 ml) are measured 6

Important Clinical Caveats

• Sample handling is critical: ACTH is unstable and requires immediate processing on ice with EDTA tubes to prevent degradation 1
• Stress and illness can elevate ACTH appropriately; a cortisol level within the normal range may be inappropriately low for the degree of stress, even when ACTH is not markedly elevated 1
• Exogenous steroids suppress ACTH and confound interpretation 1
• Cyclical Cushing's syndrome can produce variable ACTH levels, requiring confirmation of hypercortisolemia immediately prior to ACTH measurement 1
• Severely ill hospital patients occasionally exhibit morning ACTH concentrations above 200 pg/mL, representing an appropriate stress response 4