What imaging studies are recommended for diagnosing Cushing syndrome?

Imaging Studies for Cushing Syndrome

MRI of the pituitary gland with contrast is the primary imaging modality of choice for diagnosing Cushing syndrome, with 3T MRI preferred over 1.5T when available. 1

Initial Imaging for ACTH-Dependent Cushing Syndrome

Pituitary Imaging

• MRI sella without and with IV contrast is the first-line imaging study for suspected Cushing disease, with high-resolution pituitary protocols 1
• 3T MRI is preferred over 1.5T MRI where available due to improved detection of microadenomas 1
• Technical refinements that improve detection include:
  • Spoiled gradient-recalled (SPGR) acquisition echo with 1 mm slice intervals 1
  • Fluid attenuation inversion recovery (FLAIR) sequences 1
  • Constructive interference in steady state (CISS) sequences 1, 2
  • T1-weighted turbo spin echo (TSE) sequences 1
  • Contrast-enhanced CISS/FIESTA imaging, which shows superior conspicuity compared to standard T1-weighted imaging 2

Limitations of Pituitary MRI

• Despite optimal techniques, approximately one-third of MRI scans in Cushing disease patients remain negative 1
• Tumor size does not necessarily correlate with degree of hypercortisolism; patients with larger adenomas may present with milder hypercortisolism 1
• Higher resolution with 3T or 7T magnets can increase the risk of detecting incidentalomas unrelated to the disorder 1

Distinguishing Between Cushing Disease and Ectopic ACTH Syndrome

Bilateral Inferior Petrosal Sinus Sampling (BIPSS)

• BIPSS should be performed when:
  • Pituitary lesions <6 mm are detected on MRI 1
  • MRI is negative or equivocal 1
  • There is discordance between biochemical testing and imaging findings 1
• BIPSS is not necessary when pituitary tumors ≥10 mm are detected on MRI and dynamic testing results are consistent with Cushing disease 1
• For tumors 6-9 mm, expert opinions differ, but most recommend BIPSS 1
• BIPSS should be performed at specialized centers by experienced interventional radiologists 1

Additional Imaging for Suspected Ectopic ACTH Source

• When ectopic ACTH syndrome is suspected (e.g., in males with very high UFC and/or profound hypokalemia), neck-to-pelvis thin-slice CT scan is recommended 1
• 68Ga-DOTATATE PET/CT is useful for localizing ectopic ACTH-secreting neuroendocrine tumors, with approximately 65% detection rate 1

Advanced and Emerging Imaging Techniques

Functional Imaging

• PET has been explored as an alternative to or in combination with MRI for localizing corticotroph adenomas 1
• 18F-FDG PET/CT is comparable to standard fast spin echo MRI in detecting pituitary lesions 1
• PET coregistration with volumetric MRI (PET/MRCR) combines functional and anatomical imaging 1
• 11C-methionine PET may permit more accurate localization of radiotracer uptake sites 1
• Prior ovine CRH stimulation can increase 18F-FDG uptake and improve detection 1

Comparative Efficacy of Imaging Techniques

• Dynamic MRI (DMRI) may detect some adenomas not visible on conventional MRI, but with potential loss in specificity 3
• Spoiled-gradient echo 3D T1 sequences (SGE) show higher sensitivity than DMRI for detecting microadenomas 4
• Contrast-enhanced CISS/FIESTA imaging detects a higher number of pituitary microadenomas with superior conspicuity compared to T1-weighted imaging 2

Clinical Considerations and Pitfalls

• 7T MRI is not widely available and there is currently no justification for re-imaging on 7T MRI if no tumor is detected on 1.5T/3T MRI 1
• Although advanced imaging technologies may be available in some centers of excellence, the benefit of referring all patients for further imaging beyond 3T MRI remains unknown 1
• No single imaging test can absolutely differentiate between pituitary and ectopic ACTH-secreting tumors; clinical context and biochemical test results must guide management 1
• Functional imaging will likely prove a better approach than MRI alone in the future, but more data are needed to define the use of different ligands in various clinical settings 1