PNA Medical Corner: Advances in Detecting Adenomas in Cushing’s Disease

LonserThis month the PNA Medical Corner showcases a study co-authored by a member of the PNA, Dr. Russell Lonser, a neurosurgeon with Ohio State University Wexner Medical Center in Columbus, Ohio. The study finds that corticotropin-releasing hormone (CRH) can improve F-FDG-PET detection of pituitary tumors in people with Cushing’s disease.

Abstract:

Endocrine. 2019 May 6. doi: 10.1007/s12020-019-01944-7. [Epub ahead of print]

CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing's disease.
Boyle J1,2, Patronas NJ3, Smirniotopoulos J4, Herscovitch P5, Dieckman W5, Millo C5, Maric D6, Chatain GP7, Hayes CP8, Benzo S8, Scott G8, Edwards N8, Ray Chaudhury A8, Lodish MB9, Sharma S10, Nieman LK11, Stratakis CA9, Lonser RR12, Chittiboina P13,14.

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. [email protected]
14 Department of Neurosurgery, University of Colorado, Denver, CO, USA. [email protected]

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

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