Should Pituitary MRI and Abdominal CT Be Ordered for Cushing's Syndrome Investigation?
Yes, both pituitary MRI and abdominal CT should be ordered, but the sequence depends on ACTH levels—pituitary MRI is indicated for ACTH-dependent disease, while abdominal CT is indicated for ACTH-independent disease. 1, 2
Diagnostic Algorithm: ACTH-Guided Imaging Strategy
The critical first step after confirming hypercortisolism is measuring morning (08:00-09:00h) plasma ACTH levels to determine whether Cushing's syndrome is ACTH-dependent or ACTH-independent. 2, 3 This single test dictates which imaging modality to pursue:
For ACTH-Dependent Cushing's Syndrome (ACTH >5 ng/L)
Pituitary MRI is the recommended next step to identify a potential pituitary adenoma causing Cushing's disease. 2, 4 High-quality MRI with thin slices (3T MRI preferred over 1.5T where available) should be performed to maximize detection of small pituitary adenomas. 4
Interpretation of pituitary MRI findings:
- If adenoma ≥10 mm is detected: Cushing's disease is presumed and no further localization testing is needed before proceeding to treatment. 1, 2
- If adenoma 6-9 mm is detected: Most experts recommend bilateral inferior petrosal sinus sampling (BIPSS) to confirm pituitary source, though opinions differ. 1
- If no adenoma or lesion <6 mm is found: BIPSS should be performed to definitively distinguish between pituitary and ectopic ACTH sources. 2, 4
When to add abdominal/chest CT in ACTH-dependent cases: If suspicion for ectopic ACTH syndrome is high (particularly in males with very high urinary free cortisol and/or profound hypokalemia), a neck-to-pelvis thin-slice CT scan should be performed to identify neuroendocrine tumors or other ectopic sources. 1, 2
For ACTH-Independent Cushing's Syndrome (ACTH <5 ng/L or undetectable)
Abdominal CT (adrenal protocol) or MRI is indicated to identify adrenal lesion(s) such as adenoma, carcinoma, or bilateral hyperplasia. 1, 2, 3 In ACTH-independent disease, the pituitary is not the source, so pituitary MRI is not necessary. 2
Critical Pitfalls to Avoid
Do not order imaging before confirming hypercortisolism biochemically. 1 Screening tests (24-hour urinary free cortisol, late-night salivary cortisol, or overnight 1mg dexamethasone suppression test) must demonstrate elevated cortisol before proceeding to ACTH measurement and imaging. 1, 4
Do not order imaging before measuring ACTH levels. 2, 3 Ordering both pituitary MRI and abdominal CT simultaneously without knowing ACTH status is inefficient and may lead to incidental findings that confuse the diagnostic picture. 2
Recognize that pituitary MRI has limited sensitivity (63%) for detecting microadenomas. 4 Up to 40% of patients with Cushing's disease have no visible adenoma or only lesions <6mm on MRI, necessitating BIPSS for definitive diagnosis. 1, 2
Be aware that incidental pituitary lesions occur in 10% of the general population. 1 A pituitary lesion seen on MRI could be a nonfunctioning adenoma with an ectopic ACTH source elsewhere, particularly if the lesion is small and clinical presentation is atypical. 1
Special Clinical Considerations
For resistant hypertension patients: While Cushing's syndrome is uncommon in this population (<0.1%), the high morbidity and mortality of untreated disease justifies screening when clinical features are present (central obesity, wide violaceous striae, proximal muscle weakness, easy bruising). 1
Timing matters for ACTH measurement: Morning (08:00-09:00h) plasma ACTH provides optimal diagnostic accuracy, with levels >29 ng/L having 70% sensitivity and 100% specificity for Cushing's disease. 2, 3
BIPSS should only be performed at specialized centers with experienced interventional radiologists due to potential patient risk, and diagnostic criteria require central-to-peripheral ACTH ratio ≥2:1 before CRH stimulation and ≥3:1 after stimulation. 1, 2