Jacqueline Boyle1,2, Nicholas J Patronas3, James Smirniotopoulos4, Peter Herscovitch5, William Dieckman5, Corina Millo5, Dragan Maric6, Grégoire P Chatain7, Christina Piper Hayes8, Sarah Benzo8, Gretchen Scott8, Nancy Edwards8, Abhik Ray Chaudhury8, Maya B Lodish9, Susmeeta Sharma10, Lynnette K Nieman11, Constantine A Stratakis9, Russell R Lonser12, Prashant Chittiboina13,14. 1. Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA. 2. University of Illinois College of Medicine at Peoria, Peoria, IL, USA. 3. Diagnostic Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. 4. Department of Radiology, George Washington University, Washington, DC, USA. 5. Department of Positron Emission Tomography, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. 6. Flow Cytometry Core Facility, National Institute of Neurologic Diseases and Stroke, Bethesda, MD, USA. 7. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. 8. Department of Neurosurgery, University of Colorado, Denver, CO, USA. 9. Section on Endocrinology and Genetics, Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. 10. Pituitary Endocrinology Section, MedStar Washington Hospital Center, Washington, DC, USA. 11. Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. 12. Department of Neurological Surgery, The Ohio State University, Columbus, OH, USA. 13. Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA. prashant.chittiboina@nih.gov. 14. Department of Neurosurgery, University of Colorado, Denver, CO, USA. prashant.chittiboina@nih.gov.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 (clinicaltrials.gov identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 (clinicaltrials.gov identifier NCT00060541).
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 (clinicaltrials.gov identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 (clinicaltrials.gov identifier NCT00060541).
Entities:
Keywords:
CRH; Cushing’s disease; PET imaging; Pituitary adenoma; Secretagogue; Transsphenoidal surgery
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