Bo Hou1, Lu Gao2,3,4,5, Lin Shi6,7, Yishan Luo7, Xiaopeng Guo2,3, Geoffrey S Young4,5, Lei Qin4,8, Huijuan Zhu9, Lin Lu9, Zihao Wang2,3, Ming Feng2,3, Xinjie Bao2,3, Renzhi Wang2,3, Bing Xing2,3, Feng Feng1. 1. Departments of1Radiology and. 2. 2Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. 3China Pituitary Disease Registry Center, China Pituitary Adenoma Specialist Council, Beijing, China. 4. 4Department of Radiology, Harvard Medical School, Boston, Massachusetts. 5. 5Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. 6. 6Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China. 7. 7BrainNow Research Institute, Shenzhen, Guangdong Province, China. 8. 8Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts; and. 9. 9Key Laboratory of Endocrinology of the National Health Commission of the People's Republic of China, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
OBJECTIVE: Cushing's disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis. METHODS: Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence-assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery. RESULTS: Widespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05). CONCLUSIONS: This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.
OBJECTIVE:Cushing's disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CDpatient brain analysis. METHODS: Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence-assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CDpatients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery. RESULTS: Widespread brain volume loss was observed in active CDpatients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05). CONCLUSIONS: This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CDpatients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.
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