ACTH Level of 2.2 Indicates an Adrenal Source
An ACTH level of 2.2 pg/mL (or ng/L) with a positive dexamethasone suppression test definitively indicates ACTH-independent Cushing's syndrome from an adrenal source, not a pituitary source. This low ACTH level is suppressed/undetectable and rules out pituitary disease.
Understanding ACTH Levels in Cushing's Syndrome Classification
The fundamental principle in diagnosing Cushing's syndrome is that ACTH levels definitively determine whether the condition is ACTH-dependent (pituitary or ectopic) or ACTH-independent (adrenal) 1, 2.
Critical ACTH Thresholds
ACTH >5 pg/mL (or ng/L) indicates ACTH-dependent Cushing's syndrome (pituitary adenoma or ectopic ACTH source) with high certainty 1, 2, 3.
ACTH <5 pg/mL indicates ACTH-independent Cushing's syndrome from an adrenal source (adenoma, carcinoma, or hyperplasia) 2, 3.
ACTH >29 pg/mL has 70% sensitivity and 100% specificity for Cushing's disease (pituitary source) 1, 2, 3.
In ACTH-independent Cushing's syndrome, ACTH is always low and usually undetectable 1.
Your Patient's ACTH Level of 2.2
With an ACTH level of 2.2 pg/mL, this patient falls well below the threshold of 5 pg/mL, placing them squarely in the ACTH-independent category 2, 3. This suppressed ACTH level occurs because the autonomous cortisol production from the adrenal gland suppresses the normal pituitary-adrenal axis 1.
Why This Cannot Be Pituitary Disease
A pituitary adenoma (Cushing's disease) would produce elevated or at least detectable ACTH levels (>5 pg/mL) to drive the excess cortisol production 1, 3.
The presence of a measurable but low ACTH level (2.2) with confirmed hypercortisolism rules out pituitary adenoma as the diagnosis 1.
Pituitary sources account for 75-80% of ACTH-dependent cases, but they always present with elevated ACTH 1, 4.
Next Diagnostic Steps for Adrenal Source
The appropriate next step is adrenal CT or MRI to identify the adrenal lesion(s) 1, 2.
What to Look For on Imaging
Unilateral adrenal adenoma (most common cause of ACTH-independent Cushing's) - always visible on CT scan 4.
Adrenal carcinoma - may be difficult to distinguish from adenoma before surgery, but typically larger with irregular features 4.
Bilateral adrenal hyperplasia - can present as small adrenals (primary pigmented nodular adrenal dysplasia) or enlarged adrenals (ACTH-independent macronodular hyperplasia) 4.
Treatment Implications
For adrenal adenoma: laparoscopic adrenalectomy is the recommended treatment 1.
For adrenal carcinoma: open adrenalectomy with possible adjuvant therapy 1.
For bilateral hyperplasia: medical management or unilateral adrenalectomy depending on the specific condition 1.
Common Pitfalls to Avoid
Never interpret a low ACTH as "normal" in the setting of hypercortisolism - it indicates autonomous adrenal cortisol production 2.
Do not proceed with pituitary imaging or inferior petrosal sinus sampling - these are only indicated for ACTH-dependent disease (ACTH >5 pg/mL) 1, 3.
Ensure the patient is not taking exogenous glucocorticoids (oral prednisolone, dexamethasone, or even high-dose inhaled steroids), which can suppress ACTH and confuse the diagnosis 2.