Would a pituitary Magnetic Resonance Imaging (MRI) be indicated in a patient with an abnormal Dexamethasone Suppression Test (DST), normal Adrenocorticotropic Hormone (ACTH) level, and no adrenal abnormality on abdominal Computed Tomography (CT) scan?

From the Guidelines

I would strongly recommend proceeding with a pituitary MRI despite the normal ACTH level of 17, as the abnormal dexamethasone suppression test (DST) with a cortisol level of 2.1 and dexamethasone level of 397 suggests possible Cushing's syndrome, and a pituitary source remains a possibility that should be investigated. The normal ACTH level does not rule out a pituitary source, as ACTH levels in Cushing's disease can sometimes fall within the normal range due to the pulsatile nature of ACTH secretion or early disease 1. Since the abdominal CT showed no adrenal abnormality to suggest an adrenal cause of hypercortisolism, a pituitary source remains a possibility.

A pituitary MRI with thin cuts through the sella and contrast enhancement would be the appropriate next step to look for a pituitary microadenoma, as MRI remains the imaging modality of choice for ACTH-secreting pituitary adenomas 1. It is also important to note that tumor size does not necessarily correlate with degree of hypercortisolism in Cushing's disease, and patients with larger adenomas frequently present with milder hypercortisolism 1. If the MRI is negative but clinical suspicion remains high, inferior petrosal sinus sampling could be considered as a follow-up test to definitively determine if there is a pituitary source of ACTH production.

Some key points to consider when ordering the pituitary MRI include:

• Using a 3T MRI over 1.5T MRI where available, as it provides higher resolution and better detection of microadenomas 1
• Using technical refinements such as spoiled gradient–recalled (SPGR) acquisition echo with 1 mm slice intervals, fluid attenuation inversion recovery (FLAIR) and constructive interference in the steady state (CISS) to enhance detection of microadenomas 1
• Being aware that approximately one-third of scans in patients with Cushing's disease still remain negative, and higher resolution with 3T or 7T magnets can increase the risk of detecting incidentalomas potentially unrelated to the disorder 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Diagnostic Approach

The patient's abnormal dexamethasone suppression test (DST) result, with a cortisol level of 2.1 and a dexamethasone level of 397, suggests an issue with cortisol suppression. The baseline adrenocorticotropic hormone (ACTH) level was 17, which is within the normal range.

Imaging Studies

An abdominal CT with and without contrast showed no adrenal abnormality. Given the lack of adrenal findings, the next step in the diagnostic workup could involve evaluating the pituitary gland, as it plays a crucial role in regulating ACTH and subsequently cortisol production.

Considerations for Pituitary MRI

• The study 2 suggests that pituitary dynamic enhanced MRI is superior to the high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome.
• Although the patient's ACTH level is normal, the abnormal DST result warrants further investigation to rule out any pituitary abnormalities that could be causing the cortisol suppression issue.
• The decision to proceed with a pituitary MRI should be based on the clinical context and the results of previous tests, considering that a normal ACTH level does not entirely rule out pituitary involvement.

Diagnostic Tests

• The dexamethasone suppression test is a valuable tool in assessing cortisol suppression, but its interpretation can be influenced by several factors, including dexamethasone absorption and metabolism, as well as altered cortisol binding 3.
• The use of synchronous free cortisol assessment can enhance the interpretation of abnormal DST results, particularly in cases where the post-DST total cortisol is between 1.8 and 5 mcg/dL 3.

Next Steps

Given the abnormal DST result and the absence of adrenal abnormalities on CT, proceeding with a pituitary MRI could be a reasonable next step to investigate potential pituitary causes of the patient's cortisol suppression issue, despite the normal ACTH level. This approach is supported by the study 2, which highlights the value of pituitary MRI in the differential diagnosis of ACTH-dependent Cushing's syndrome.