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