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

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Citation: Endocrine. 65(1):155-165, 2019 07.PMID: 31062234Institution: MedStar Washington Hospital CenterDepartment: Medicine/EndocrinologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *ACTH-Secreting Pituitary Adenoma/di [Diagnosis] | *Adenoma/di [Diagnosis] | *Corticotropin-Releasing Hormone/me [Metabolism] | *Fluorodeoxyglucose F18 | *Pituitary ACTH Hypersecretion/di [Diagnosis] | *Positron-Emission Tomography/mt [Methods] | ACTH-Secreting Pituitary Adenoma/me [Metabolism] | ACTH-Secreting Pituitary Adenoma/pa [Pathology] | Adenoma/me [Metabolism] | Adenoma/pa [Pathology] | Adolescent | Adult | Child | Diagnosis, Differential | Female | Humans | Male | Middle Aged | Pituitary ACTH Hypersecretion/me [Metabolism] | Pituitary ACTH Hypersecretion/pa [Pathology] | Sensitivity and Specificity | Young AdultYear: 2019ISSN:
  • 1355-008X
Name of journal: EndocrineAbstract: CLINICAL TRIAL INFORMATION: <sup>18</sup>F-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).CONCLUSIONS: The results of the current study suggest that oCRH-stimulation may lead to increased <sup>18</sup>F-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.METHODS: Subjects with a likely diagnosis of CD (n = 27, 20 females) each underwent two <sup>18</sup>F-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 <sup>18</sup>F-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins.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. <sup>18</sup>F-fluoro-deoxy-glucose (<sup>18</sup>F-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 <sup>18</sup>F-FDG-PET detection of adenomas in CD.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.All authors: Benzo S, Boyle J, Chatain GP, Chittiboina P, Dieckman W, Edwards N, Hayes CP, Herscovitch P, Lodish MB, Lonser RR, Maric D, Millo C, Nieman LK, Patronas NJ, Ray Chaudhury A, Scott G, Sharma S, Smirniotopoulos J, Stratakis CAOriginally published: Endocrine. 65(1):155-165, 2019 Jul.Fiscal year: FY2020Digital Object Identifier: Date added to catalog: 2019-05-21
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Journal Article MedStar Authors Catalog Article 31062234 Available 31062234

CLINICAL TRIAL INFORMATION: <sup>18</sup>F-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).

CONCLUSIONS: The results of the current study suggest that oCRH-stimulation may lead to increased <sup>18</sup>F-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.

METHODS: Subjects with a likely diagnosis of CD (n = 27, 20 females) each underwent two <sup>18</sup>F-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 <sup>18</sup>F-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins.

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. <sup>18</sup>F-fluoro-deoxy-glucose (<sup>18</sup>F-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 <sup>18</sup>F-FDG-PET detection of adenomas in CD.

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.

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