Pituitary MRI is the Recommended Next Imaging Study
For this patient with confirmed ACTH-dependent Cushing's syndrome (cortisol 2.2 μg/dL after 1mg dexamethasone, ACTH 15 pg/mL, DHEAS 190 μg/dL), pituitary MRI with contrast using 3T imaging where available is the appropriate next imaging step. 1
Understanding the Clinical Picture
Your patient has failed the 1mg dexamethasone suppression test with a cortisol of 2.2 μg/dL (normal suppression is <1.8 μg/dL), confirming hypercortisolism. 1 The ACTH level of 15 pg/mL is detectable and indicates ACTH-dependent Cushing's syndrome, as any ACTH >5 pg/mL in the setting of confirmed hypercortisolism points to an ACTH-dependent etiology. 2 The DHEAS level of 190 μg/dL is within normal range and does not suggest adrenal carcinoma or ectopic ACTH syndrome, which typically present with very high or very low DHEAS levels respectively.
Why Pituitary MRI is the Correct Next Step
- Pituitary adenomas (Cushing's disease) account for 75-80% of all ACTH-dependent Cushing's syndrome cases, making this statistically the most likely diagnosis. 2
- MRI remains the imaging modality of choice for ACTH-secreting pituitary adenomas, with high-quality imaging using 3T MRI preferred over 1.5T where available to maximize detection of microadenomas. 1
- The imaging protocol should include spoiled gradient-recalled (SPGR) acquisition with 1mm slice intervals, fluid attenuation inversion recovery (FLAIR), and constructive interference in the steady state (CISS) sequences to enhance detection of small lesions. 1
Important Caveats About Pituitary MRI
- Approximately one-third of pituitary MRIs in patients with Cushing's disease remain negative, even with optimal imaging techniques, because most ACTH-secreting adenomas are microadenomas ≤2mm in diameter. 1
- Tumor size does not correlate with degree of hypercortisolism - patients with larger adenomas frequently present with milder hypercortisolism. 1
- The risk of detecting incidentalomas (unrelated pituitary lesions) increases with higher resolution imaging, which can complicate interpretation. 1
Algorithmic Approach Based on MRI Results
If MRI Shows Adenoma ≥10mm
- Proceed directly to transsphenoidal surgery without additional testing, as this strongly suggests Cushing's disease. 2
If MRI Shows Adenoma 6-9mm
- Consider additional confirmatory testing such as CRH stimulation test or desmopressin stimulation before proceeding to surgery or bilateral inferior petrosal sinus sampling (BIPSS). 2
If MRI is Normal or Shows Lesion <6mm
- BIPSS is the gold standard next step to definitively distinguish between pituitary Cushing's disease and ectopic ACTH syndrome. 1, 2
- BIPSS should be performed at a specialized center by an experienced interventional radiologist due to potential patient risks. 1
- Diagnostic criteria: central-to-peripheral ACTH ratio ≥2:1 at baseline or ≥3:1 after CRH or desmopressin stimulation confirms pituitary source with 96-100% sensitivity. 2
When to Consider Ectopic ACTH Syndrome
While less likely in this patient, consider ectopic ACTH syndrome if:
- Very high urinary free cortisol levels (>4-5 times upper limit of normal) 2
- Profound hypokalemia with metabolic alkalosis 3, 4
- Rapid onset of symptoms with severe hypercortisolism 3
- Marked skin pigmentation 3
If clinical suspicion for ectopic ACTH is high despite normal pituitary MRI, obtain neck-to-pelvis thin-slice CT scan and consider 68Ga-DOTATATE PET imaging to localize neuroendocrine tumors. 1, 2
Critical Clinical Considerations
- Do not order adrenal imaging - the detectable ACTH level rules out primary adrenal causes (adrenal adenoma or carcinoma), which would present with suppressed ACTH levels <5 pg/mL. 2
- Ensure the patient is in an active hypercortisolemic phase if cyclic Cushing's is suspected, as BIPSS and other localization procedures require confirmed active disease at the time of testing. 1
- Stop any medical therapy for Cushing's syndrome (steroidogenesis inhibitors) before performing BIPSS to enable accurate interpretation. 2