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Published in: Endocrine 1/2019

01-07-2019 | Pituitary Adenoma | Original Article

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

Authors: 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 Chittiboina

Published in: Endocrine | Issue 1/2019

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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).
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Metadata
Title
CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing’s disease
Authors
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 Chittiboina
Publication date
01-07-2019
Publisher
Springer US
Published in
Endocrine / Issue 1/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-01944-7

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