Amit Tirosh1,2, Harish RaviPrakash3, Georgios Z Papadakis4,5,6, Christina Tatsi1, Elena Belyavskaya1, Lyssikatos Charalampos1, Maya B Lodish1, Ulas Bagci3, Constantine A Stratakis1. 1. Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. 2. NET Service and Endocrine Oncology Bioinformatics Lab, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel. 3. Center for Research in Computer Vision (CRCV), University of Central Florida, Orlando, Florida. 4. Computational Biomedicine Laboratory (CBML), Institute of Computer Science (ICS), Foundation for Research and Technology (FORTH), Heraklion, Crete, Greece. 5. Skeletal Clinical Studies Unit, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, Maryland. 6. Department of Medical Imaging, Heraklion University Hospital, Medical School, University of Crete, Heraklion, Crete, Greece.
Abstract
BACKGROUND: Young patients with Cushing Syndrome (CS) may develop cognitive and behavioral alterations during disease course. METHODS: To investigate the effects of CS on the brain, we analyzed consecutive MRI scans of patients with (n = 29) versus without CS (n = 8). Multiple brain compartments were processed for total and gray/white matter (GM/WM) volumes and intensities, and cortical volume, thickness, and surface area. Dynamics (last/baseline scans ratio per parameter) were analyzed versus cortisol levels and CS status (persistent, resolved, and non-CS). RESULTS: Twenty-four-hour urinary free cortisol (24hUFC) measurements had inverse correlation with the intensity of subcortical GM structures and of the corpus callosum, and with the cerebral WM intensity. 24hUFC dynamics had negative correlation with volume dynamics of multiple cerebral and cerebellar structures. Patients with persistent CS had less of an increase in cortical thickness and WM intensity, and less of a decrease in WM volume compared with patients with resolution of CS. Patients with resolution of their CS had less of an increase in subcortical GM and cerebral WM volumes, but a greater increase in cortical thickness of frontal lobe versus controls. CONCLUSION: Changes in WM/GM consistency, intensity, and homogeneity in patients with CS may correlate with CS clinical consequences better than volume dynamics alone. Published by Oxford University Press on behalf of the Endocrine Society 2019.
BACKGROUND: Young patients with Cushing Syndrome (CS) may develop cognitive and behavioral alterations during disease course. METHODS: To investigate the effects of CS on the brain, we analyzed consecutive MRI scans of patients with (n = 29) versus without CS (n = 8). Multiple brain compartments were processed for total and gray/white matter (GM/WM) volumes and intensities, and cortical volume, thickness, and surface area. Dynamics (last/baseline scans ratio per parameter) were analyzed versus cortisol levels and CS status (persistent, resolved, and non-CS). RESULTS: Twenty-four-hour urinary free cortisol (24hUFC) measurements had inverse correlation with the intensity of subcortical GM structures and of the corpus callosum, and with the cerebral WM intensity. 24hUFC dynamics had negative correlation with volume dynamics of multiple cerebral and cerebellar structures. Patients with persistent CS had less of an increase in cortical thickness and WM intensity, and less of a decrease in WM volume compared with patients with resolution of CS. Patients with resolution of their CS had less of an increase in subcortical GM and cerebral WM volumes, but a greater increase in cortical thickness of frontal lobe versus controls. CONCLUSION: Changes in WM/GM consistency, intensity, and homogeneity in patients with CS may correlate with CS clinical consequences better than volume dynamics alone. Published by Oxford University Press on behalf of the Endocrine Society 2019.
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