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Steroids ; 151: 108457, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31326450


The adverse effects of hypercortisolism on the human brain have been highlighted in previous studies of Cushing's disease (CD). However, the reversibility of brain damage after the resolution of hypercortisolism remains unclear. Thus, we studied the potential volumetric reversibility in biochemically remitted CD patients. Cross-sectional analysis demonstrated the active CD patients (n = 61) had the smallest gray matter (GM) volumes (553.33 ±â€¯45.90 CM3) among four groups. While the GM volumes of short-term remitted CD patients (586.62 ±â€¯46.89 CM3, n = 28) and long-term remitted CD patients (596.58 ±â€¯45.95 CM3, n = 35) were between those of the active CD patients and healthy control subjects (628.14 ±â€¯46.88 CM3, n = 74). Moreover, significant positive correlations between remitted time and GM volumes were only found in short-term remitted CD patients. On the contrary, the alterations of white matter (WM) in CD patients seem to be independent of concomitant hypercortisolism, persisting after remission. A preliminary longitude analysis also demonstrated similar results. Volumetric reversibility of GM, but not WM is highly prevalent in short-term after resolution of hypercortisolism in Cushing disease. Our study enhances our understanding of the reversible and the irreversible structural alterations in the human brain due to hypercortisolism.

Endocr Pract ; 25(6): 534-544, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30865546


Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width.

Diabetes Insípido Neurogênico , Hipopituitarismo , Doenças da Hipófise , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Hipófise
Neuroimage Clin ; 22: 101691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30708349


BACKGROUND: Computerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated. METHOD: MCI patients in the training group were asked to take training 3-4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again. RESULTS: 78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant. CONCLUSIONS: Multi-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.

Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/reabilitação , Remediação Cognitiva/métodos , Terapia Assistida por Computador/métodos , Idoso , Córtex Cerebral/diagnóstico por imagem , China , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
Clin Endocrinol (Oxf) ; 87(4): 367-374, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28543178


OBJECTIVE: The data on patients with short-term remission of Cushing's disease (CD) might provide information that is not available from previous long-term remission studies. We aimed to investigate structural changes in the brain in these patients and to examine whether these changes were associated with clinical characteristics. DESIGN: A cross-sectional study was performed. METHODS: Thirty-four patients with CD (14 with CD in short-term remission and 20 with active CD) and 34 controls matched for age, sex and education underwent clinical evaluation and magnetic resonance imaging brain scans. Biometric measurements, disease duration and remission duration data were collected. Grey matter volumes in the whole brain were examined using voxel-based morphometry (VBM). RESULTS: No differences were observed in the grey matter volumes of the medial frontal gyrus (MFG) and cerebellum between the patients with remitted CD and healthy controls, whereas patients with active CD had smaller grey matter volumes in these two regions compared with controls and patients with remitted CD. Furthermore, significant correlations were found between remission time and grey matter values in these regions in short-term remission patients with CD. Additionally, greater grey matter volumes in the bilateral caudate of short-term remission patients with CD were observed. CONCLUSIONS: Trends for structural restoration were found in CD patients with short-term remission. This finding was associated with the number of days elapsed since curative surgery and the current age of the patients. This study enhances our understanding of potential reversibility after the resolution of hypercortisolism in CD patients.

Imagem por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Adulto , Estudos Transversais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Adulto Jovem
Brain Res ; 1665: 80-87, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28438531


Exposure to chronic hypercortisolism has multiple adverse effects on brain biology in humans. Cushing's disease (CD) represents a unique and natural human model for examining the effects of hypercortisolism on the brain. This cross-sectional study used Diffusional Kurtosis Imaging (DKI) to investigate the microstructure alterations in both white matter (WM) and gray matter (GM) of CD patients and to determine the relationship of these changes with clinical characteristics. DKI images were obtained from 15 active CD patients. DKI parametric maps were estimated through voxel-based analyses (VBA) and compared with 15 healthy controls matched for age, sex and education. In addition, correlations were analyzed between the altered DKI parameters and clinical characteristics. Compared with healthy controls, CD patients mainly exhibited significantly altered diffuse parameters in the GM and WM of the left medial temporal lobe (MTL). The mean values of increased radial diffusivity (RD) of CD patients in GM of the left hippocampus/parahippocampal gyrus correlated positively with the clinical severity of CD. Additionally, we also found altered kurtosis parameters in the cerebellum and frontal lobe. DKI imaging of CD patients could represent complementary information in both white matter and gray matter. The impairment of the left MTL might explain some part of the memory and cognition impairments in CD patients.

Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Algoritmos , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade
Clin Endocrinol (Oxf) ; 86(3): 367-376, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27859451


CONTEXT AND OBJECTIVE: Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. SUBJECTS AND METHODS: Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. RESULTS: Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. CONCLUSIONS: This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies.

Encéfalo/fisiopatologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Adulto Jovem