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

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

doi:10.1007/s12020-019-01944-7

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

Endocrine. 2019 Jul;65(1):155-165. doi: 10.1007/s12020-019-01944-7. Epub 2019 May 6.

Authors

Jacqueline Boyle^{1

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 Chittiboina^{13

14}

Affiliations

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.

PMID: 31062234
DOI: 10.1007/s12020-019-01944-7

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).

Keywords: CRH; Cushing’s disease; PET imaging; Pituitary adenoma; Secretagogue; Transsphenoidal surgery.

Publication types

Clinical Trial
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

ACTH-Secreting Pituitary Adenoma / diagnosis*
ACTH-Secreting Pituitary Adenoma / metabolism
ACTH-Secreting Pituitary Adenoma / pathology
Adenoma / diagnosis*
Adenoma / metabolism
Adenoma / pathology
Adolescent
Adult
Child
Corticotropin-Releasing Hormone / metabolism*
Diagnosis, Differential
Female
Fluorodeoxyglucose F18*
Humans
Male
Middle Aged
Pituitary ACTH Hypersecretion / diagnosis*
Pituitary ACTH Hypersecretion / metabolism
Pituitary ACTH Hypersecretion / pathology
Positron-Emission Tomography / methods*
Sensitivity and Specificity
Young Adult

Substances

Fluorodeoxyglucose F18
Corticotropin-Releasing Hormone

Associated data

ClinicalTrials.gov/NCT01459237
ClinicalTrials.gov/NCT00060541

Grants and funding

NS003150-01/NH/NIH HHS/United States