What does an Adrenocorticotropic hormone (ACTH) level of 23 indicate?

Interpretation of ACTH Level of 23

An ACTH level of 23 pg/mL (or ng/L) falls within the normal to slightly elevated range and requires correlation with cortisol levels and clinical context to determine its significance. The interpretation depends critically on whether this represents morning sampling and the accompanying cortisol value.

Diagnostic Framework

Normal Reference Context

• Normal morning ACTH ranges from approximately 9-77 ng/L in most assays, with tighter ranges of 9-24 ng/L specifically between 9:00-9:30 AM 1
• An ACTH of 23 is at the upper end of the strict morning normal range but within broader normal limits 1
• Timing of sample collection is critical—ACTH exhibits diurnal variation and must be interpreted based on time of day 1

Clinical Scenarios by Cortisol Correlation

If Cortisol is Low (< 3 mcg/dL):

• This combination (normal-range ACTH with low cortisol) suggests secondary adrenal insufficiency 2, 3
• In secondary AI, ACTH is inappropriately normal or low when cortisol is deficient—the pituitary fails to mount an appropriate ACTH response 3
• Evaluate for pituitary pathology: obtain TSH, FT4, LH, FSH, and sex hormones to assess for hypopituitarism 3
• Consider MRI of the pituitary/sella if multiple hormone deficiencies are present 3
• If immune checkpoint inhibitor exposure exists, hypophysitis-induced isolated ACTH deficiency is likely 2, 4

If Cortisol is Elevated (> 15 mcg/dL):

• An ACTH of 23 with elevated cortisol indicates ACTH-dependent Cushing's syndrome 2, 5
• This distinguishes from adrenal tumors, which suppress ACTH to undetectable or very low levels 2
• Elevated ACTH (>5 ng/L) with hypercortisolism suggests either pituitary Cushing's disease or ectopic ACTH secretion 5
• Ectopic ACTH syndrome typically produces higher ACTH levels (mean 0.42 mU/100 mL or higher), though overlap exists 6
• Proceed with pituitary MRI and consider bilateral inferior petrosal sinus sampling (BIPSS) to localize the source 5

If Cortisol is Indeterminate (3-15 mcg/dL):

• Perform ACTH stimulation test to assess adrenal reserve 2
• A peak cortisol ≥20 mcg/dL indicates normal adrenal function 7
• If stimulation test is abnormal, this supports adrenal insufficiency requiring further workup 2

Key Diagnostic Pitfalls

Common Errors to Avoid:

• Never interpret ACTH in isolation—always correlate with simultaneous cortisol and clinical presentation 2, 3
• Failure to note exact sampling time can lead to misinterpretation, as ACTH >24 ng/L at 9 AM may be abnormal despite being within broader reference ranges 1
• In immune checkpoint inhibitor patients, watch for subtle early signs: eosinophilia and mild hyponatremia may precede overt adrenal insufficiency 4
• ACTH levels in Cushing's disease overlap significantly with normal ranges—dynamic testing (dexamethasone suppression, CRH stimulation) is essential for diagnosis 5, 6

Electrolyte Assessment:

• Obtain basic metabolic panel to evaluate for hyponatremia and hyperkalemia, which suggest adrenal insufficiency 2, 3
• Check renin and aldosterone if primary AI is considered, though ACTH of 23 makes this less likely 2

Immediate Clinical Actions

If symptoms of adrenal insufficiency are present (fatigue, anorexia, weight loss, hypotension):

• Initiate hydrocortisone 15-20 mg in divided doses immediately while awaiting confirmatory testing 2
• Obtain endocrine consultation urgently 2, 3
• For severe symptoms, hospitalize and administer IV hydrocortisone 100 mg or dexamethasone 4 mg with IV fluids 3

If hypercortisolism is suspected (hypertension, hyperglycemia, central obesity):

• Confirm with 24-hour urinary free cortisol or late-night salivary cortisol 5
• Proceed with imaging and source localization as above 5