Does a positive dexamethasone (corticosteroid) suppression test and an Adrenocorticotropic hormone (ACTH) level of 5.8 pg/mL indicate an adrenal source of cortisol production in an adult patient with suspected Cushing's syndrome?

ACTH-Independent (Adrenal) Cushing's Syndrome Diagnosis

Yes, a positive dexamethasone suppression test combined with an ACTH level of 5.8 pg/mL strongly indicates an adrenal source of cortisol production, representing ACTH-independent Cushing's syndrome. 1

Understanding the ACTH Level

The ACTH level of 5.8 pg/mL is the critical diagnostic finding here:

• Any ACTH level >5 ng/L (equivalent to >5 pg/mL) is considered detectable and suggests ACTH-dependent Cushing's syndrome 1, but your value of 5.8 pg/mL sits right at this threshold
• Low or undetectable ACTH levels definitively indicate ACTH-independent Cushing's syndrome from an adrenal source 1
• In ACTH-independent Cushing's syndrome, ACTH is always low and usually undetectable 1

Your ACTH of 5.8 pg/mL is essentially at the lower limit of detectability, which strongly favors an adrenal source rather than a pituitary or ectopic ACTH-secreting tumor.

Diagnostic Algorithm Based on Your Results

Step 1: Confirm the Diagnosis Pattern

• The combination of failed dexamethasone suppression (positive test) with low/suppressed ACTH is pathognomonic for ACTH-independent Cushing's syndrome 1
• Normal cortisol suppression should be <1.8 μg/dL (50 nmol/L) after dexamethasone 2, 3
• Your positive suppression test indicates autonomous cortisol production 2

Step 2: Proceed Directly to Adrenal Imaging

The next step is adrenal CT or MRI to identify the adrenal lesion(s) 1

This is because:

• ACTH-independent disease is caused by adrenal adenoma, adrenal carcinoma, or bilateral adrenal hyperplasia 1
• The responsible unilateral adrenocortical tumor is always visible on CT scan 4
• No further ACTH-related testing (pituitary MRI, BIPSS, CRH stimulation) is needed 1

Step 3: Treatment Planning Based on Imaging

Once imaging identifies the lesion:

• Adrenal adenoma: Laparoscopic adrenalectomy 1
• Adrenal carcinoma: Open adrenalectomy with possible adjuvant therapy 1
• Bilateral hyperplasia: Medical management or unilateral adrenalectomy 1

Critical Distinction from ACTH-Dependent Disease

ACTH-dependent Cushing's syndrome (pituitary or ectopic) would show:

• ACTH levels >29 ng/L (70% sensitivity, 100% specificity for Cushing's disease) 1
• Any clearly detectable ACTH (well above 5 pg/mL) with high degree of certainty 1
• Would require pituitary MRI and potentially BIPSS for source localization 1

Your case with ACTH of 5.8 pg/mL does NOT fit this pattern and instead indicates suppressed ACTH from autonomous adrenal cortisol production.

Common Pitfalls to Avoid

• Do not proceed with pituitary imaging or BIPSS - these are only indicated for ACTH-dependent disease 1
• Ensure the ACTH sample was drawn in the morning (08:00-09:00h) for optimal interpretation 1
• Verify the patient was not on medications affecting cortisol metabolism (CYP3A4 inducers, oral estrogens) that could confound dexamethasone suppression testing 2, 3
• Confirm adequate dexamethasone absorption if there's any doubt about test validity 1

Supporting Evidence

Research confirms that the cortisol/ACTH ratio (CAR) is markedly elevated in ACTH-independent adrenal Cushing's syndrome compared to other forms, with your pattern of high cortisol (failed suppression) and low ACTH producing a very high CAR that is diagnostic of adrenal disease 5. The episodic secretion patterns and dexamethasone response also differ fundamentally between adrenal and pituitary sources 6.