Optimal Timing for ACTH Measurement in Pituitary Adenoma Assessment
Morning plasma ACTH levels (08:00-09:00h) should be measured for initial assessment of pituitary adenomas, particularly when evaluating for Cushing's disease, as this timing provides the most reliable diagnostic information. 1
Diagnostic Algorithm for ACTH Measurement
- Morning (08:00-09:00h) plasma ACTH measurement is the optimal time for initial assessment of pituitary adenomas, particularly for Cushing's disease evaluation 1
- In patients with confirmed hypercortisolism, a morning ACTH level >5 ng/L (>1.1 pmol/L) is detectable in all patients with Cushing's disease 1
- Using a cut-off value of 29 ng/L (6.4 pmol/L), morning ACTH has 70% sensitivity and 100% specificity for diagnosing Cushing's disease in the presence of confirmed hypercortisolism 1, 2
- In ACTH-independent Cushing's syndrome, ACTH is always low and usually undetectable 1
Special Considerations for ACTH Measurement
- For patients with cyclical Cushing's disease, hypercortisolemia must be confirmed immediately prior to diagnostic procedures like bilateral inferior petrosal sinus sampling (BIPSS) to ensure the patient is in an active disease phase 1, 3
- Medical therapy for Cushing's disease (steroidogenesis inhibitors) must be stopped before undertaking BIPSS to enable accurate interpretation of results 1
- For patients with inconclusive MRI findings, BIPSS should be performed to confirm a pituitary source of ACTH excess 1, 4
- During BIPSS, a pituitary source of ACTH excess is confirmed by a central-to-peripheral ACTH ratio ≥2:1 before CRH or desmopressin and ≥3:1 after stimulation 1, 3
Diagnostic Pitfalls and Caveats
- Midnight cortisol measurements may be influenced by non-suppressed ACTH levels, potentially leading to false-positive results for hypercortisolism in patients with adrenal incidentaloma 5
- Measurement of midnight ACTH levels alongside midnight cortisol can help distinguish true hypercortisolism from false positives 5
- Ectopic ACTH-secreting pituitary adenomas (outside the sella) can be missed if only sellar imaging is performed, requiring thorough evaluation of any patient with Cushing's syndrome symptoms without obvious pituitary adenoma 6
- The coincident existence of a sellar mass should not preclude the possibility of an ectopic source of ACTH 6
Clinical Implications
- Accurate assessment of ACTH levels is critical for distinguishing between ACTH-dependent and ACTH-independent forms of Cushing's syndrome 2, 4
- For ACTH-dependent Cushing's syndrome with no identified adenoma on pituitary MRI, BIPSS should be offered to confirm a central source of ACTH excess 1
- BIPSS should only be performed in a specialist center with expertise in such testing and by an experienced interventional radiologist 1
- BIPSS may also provide information on tumor lateralization if the inter-petrosal sinus ACTH gradient after CRH or desmopressin stimulation is ≥1.4 between the two sides 1
By following this algorithm for ACTH measurement timing and interpretation, clinicians can optimize the diagnostic accuracy for pituitary adenomas, particularly in cases of suspected Cushing's disease, leading to improved patient outcomes through appropriate and timely treatment.