CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing’s disease
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 (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).
KeywordsPituitary 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 http://fnih.org/work/ education-training-0/medical-research-scholars-program.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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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