, Volume 65, Issue 1, pp 155–165 | Cite as

CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing’s disease

  • Jacqueline Boyle
  • Nicholas J. Patronas
  • James Smirniotopoulos
  • Peter Herscovitch
  • William Dieckman
  • Corina Millo
  • Dragan Maric
  • Grégoire P. Chatain
  • Christina Piper Hayes
  • Sarah Benzo
  • Gretchen Scott
  • Nancy Edwards
  • Abhik Ray Chaudhury
  • Maya B. Lodish
  • Susmeeta Sharma
  • Lynnette K. Nieman
  • Constantine A. Stratakis
  • Russell R. Lonser
  • Prashant ChittiboinaEmail author
Original Article



In MRI-negative cases Cushing’s disease (CD), surgeons perform a more extensive exploration of the pituitary gland, with fewer instances of hormonal remission. 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) has a limited role in detecting adenomas that cause CD (corticotropinomas). Our previous work demonstrated corticotropin-releasing hormone (CRH) stimulation leads to delayed, selective glucose uptake in corticotropinomas. Here, we prospectively evaluated the utility of CRH stimulation in improving 18F-FDG-PET detection of adenomas in CD.


Subjects with a likely diagnosis of CD (n = 27, 20 females) each underwent two 18F-FDG-PET studies [without and with ovine-CRH (oCRH) stimulation] on a high-resolution PET platform. Standardized-uptake-values (SUV) in the sella were calculated. Two blinded neuroradiologists independently read 18F-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins.


The mean-SUV of adenomas was significantly increased from baseline (3.6 ± 1.5) with oCRH administration (3.9 ± 1.7; one-tailed p = 0.003). Neuroradiologists agreed that adenomas were visible on 21 scans, not visible on 26 scans (disagreed about 7, kappa = 0.7). oCRH-stimulation led to the detection of additional adenomas (n = 6) not visible on baseline-PET study. Of the MRI-negative adenomas (n = 5), two were detected on PET imaging (one only after oCRH-stimulation). USP8 mutations or glycolytic pathway proteins were not associated with SUV in corticotropinomas.


The results of the current study suggest that oCRH-stimulation may lead to increased 18F-FDG uptake, and increased rate of detection of corticotropinomas in CD. These results also suggest that some MRI invisible adenomas may be detectable by oCRH-stimulated FDG-PET imaging.

Clinical trial information

18F-FDG-PET imaging with and without CRH stimulation was performed under the clinical trial NIH ID 12-N-0007 ( identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 ( identifier NCT00060541).


Pituitary adenoma PET imaging Cushing’s disease Transsphenoidal surgery CRH Secretagogue 



This work was supported by National Institutes of Health Intramural Grant ZIA NS003150-01 awarded to Prashant Chittiboina. This work was also supported by the Intramural Research Programs of the National Institute of Neurological Diseases and Stroke, National Institutes of Health Clinical Center, the National Institute of Diabetes and Digestive and Kidney Disorders, and Eunice Kennedy Shriver National Institute for Child Health and Human Development, Bethesda, MD. J.B. was supported by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH. For a complete list of donors, please visit education-training-0/medical-research-scholars-program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Combined Neuroscience Institutional Review Board of the NIH and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2019

Authors and Affiliations

  • Jacqueline Boyle
    • 1
    • 2
  • Nicholas J. Patronas
    • 3
  • James Smirniotopoulos
    • 4
  • Peter Herscovitch
    • 5
  • William Dieckman
    • 5
  • Corina Millo
    • 5
  • Dragan Maric
    • 6
  • Grégoire P. Chatain
    • 7
  • Christina Piper Hayes
    • 8
  • Sarah Benzo
    • 8
  • Gretchen Scott
    • 8
  • Nancy Edwards
    • 8
  • Abhik Ray Chaudhury
    • 8
  • Maya B. Lodish
    • 9
  • Susmeeta Sharma
    • 10
  • Lynnette K. Nieman
    • 11
  • Constantine A. Stratakis
    • 9
  • Russell R. Lonser
    • 12
  • Prashant Chittiboina
    • 1
    • 8
    Email author
  1. 1.Neurosurgery Unit for Pituitary and Inheritable DiseasesNational Institute of Neurological Diseases and StrokeBethesdaUSA
  2. 2.University of Illinois College of Medicine at PeoriaPeoriaUSA
  3. 3.Diagnostic Radiology, Warren Grant Magnuson Clinical CenterNational Institutes of HealthBethesdaUSA
  4. 4.Department of RadiologyGeorge Washington UniversityWashingtonUSA
  5. 5.Department of Positron Emission Tomography, Warren Grant Magnuson Clinical CenterNational Institutes of HealthBethesdaUSA
  6. 6.Flow Cytometry Core FacilityNational Institute of Neurologic Diseases and StrokeBethesdaUSA
  7. 7.Surgical Neurology BranchNational Institute of Neurological Disorders and StrokeBethesdaUSA
  8. 8.Department of NeurosurgeryUniversity of ColoradoDenverUSA
  9. 9.Section on Endocrinology and Genetics, Pediatric Endocrinology Inter-Institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBethesdaUSA
  10. 10.Pituitary Endocrinology SectionMedStar Washington Hospital CenterWashingtonUSA
  11. 11.Diabetes, Endocrinology and Obesity BranchNational Institute of Diabetes and Digestive and Kidney DiseasesBethesdaUSA
  12. 12.Department of Neurological SurgeryThe Ohio State UniversityColumbusUSA

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