Bilateral inferior petrosal sinus sampling for the treatment of Cushing's disease Data from 52 cases from one institute over an eight-year period

The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferior petrosal sinus sampling （BIPSS）. Of the 108 patients 52 underwent BIPSS prior to surgery and 56 did not. Results showed that BIPSS accuracy for the diagnosis of Cushing＇s disease was 86.5% （45/52）, and accuracy for adenoma lateralization during surgery was 76.9% （40/52）. In addition, early remission rate was significantly greater compared to patients without BIPSS. Results demonstrated that BIPSS facilitated localization and diagnosis of Cushing＇s disease and helped to predict adenoma lateralization.

Role of adrenalectomy in treating recurrent Cushing's disease:A report of 43 cases

Objective To evaluate the efficacy of laparoscopic adrenalectomy and open adrenalectomy in treating recurrent Cushing ’s disease. Methods Forty-three patients ( 29 females and 14 males) with recurrent Cushing’s disease treated with laparoscopic adrenalectomy ( LA,n = 32) or open ( OA,n = 11) adrenalectomy from 2000

GAN-DIRNet:A Novel Deformable Image Registration Approach for Multimodal Histological Images

Multi-modal histological image registration tasks pose significant challenges due to tissue staining operations causing partial loss and folding of tissue.Convolutional neural network(CNN)and generative adversarial network(GAN)are pivotal inmedical image registration.However,existing methods often struggle with severe interference and deformation,as seen in histological images of conditions like Cushing’s disease.We argue that the failure of current approaches lies in underutilizing the feature extraction capability of the discriminator inGAN.In this study,we propose a novel multi-modal registration approach GAN-DIRNet based on GAN for deformable histological image registration.To begin with,the discriminators of two GANs are embedded as a new dual parallel feature extraction module into the unsupervised registration networks,characterized by implicitly extracting feature descriptors of specific modalities.Additionally,modal feature description layers and registration layers collaborate in unsupervised optimization,facilitating faster convergence and more precise results.Lastly,experiments and evaluations were conducted on the registration of the Mixed National Institute of Standards and Technology database(MNIST),eight publicly available datasets of histological sections and the Clustering-Registration-Classification-Segmentation(CRCS)dataset on the Cushing’s disease.Experimental results demonstrate that our proposed GAN-DIRNet method surpasses existing approaches like DIRNet in terms of both registration accuracy and time efficiency,while also exhibiting robustness across different image types.

Neuropsychiatric disorders and cognitive dysfunction in patients with Cushing＇s disease

Objective To review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing＇s disease （CD） and the associated pathophysiological mechanisms underlying CD.These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD.Data sources Data were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years.To perform the PubMed literature search,the following keywords were input：cushing＇s disease,cognitive,hippocampal,or glucocorticoids.Study selection Studies were selected if they contained data relevant to the topic addressed in the particular section.Because of the limited length of this article,we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers.Results Patients with active CD not only suffer from many characteristic clinical features,but also show some neuropsychiatric disorders and cognitive impairments.Among the psychiatric manifestations,the common ones are emotional instability,depressive disorder,anxious symptoms,impulsivity,and cognitive impairment.Irreversible effects of previous glucocorticoid （GC） excess on the central nervous system,such as hippocampal and the basal ganglia,is the most reasonable reason.Excess secretion of cortisol brings much structural and functional changes in hippocampal,such as changes in neurogenesis and morphology,signaling pathway,gene expression,and glutamate accumulation.Hippocampal volume loss can be found in most patients with CD,and decreased glucose utilization caused by GCs may lead to brain atrophy,neurogenesis impairment,inhibition of long-term potentiation,and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes.Conclusions Brain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant pathophysiological role in the etiology of changes in cognitive function and psychiatric disturbances.The exact mechanisms by which GCs induce hippocampal volume loss are not very clear till now.So,further investigations into the mechanisms by which GCs affect the brain and the effective coping strategy are essential.

Role of adrenalectomy in recurrent Cushing＇s disease

Background Cushing＇s disease is a pituitary-dependent type of Cushing＇s syndrome. Treatment consists of pituitary surgery or radiotherapy, but the recurrence rate at 10 years is as high as 40%. Adrenalectomy is considered an effective treatment to refractory Cushing＇s disease. The objective of this study was to examine the efficacy of laparoscopic adrenalectomy and open adrenalectomy in Cushing＇s disease, focusing on reversing the sequelae of hypercortisolism and improving patients＇ quality of life. Methods Forty-three patients （29 women, 14 men） with recurrent Cushing＇s disease after transsphenoidal operation underwent laparoscopic （n=32） or open （n=11） adrenalectomy from 2000 to 2008. Surgical results were evaluated for all the 43 patients. Patients completed a follow-up survey, including the short-form 36-item （SF-36） health survey. Results All the 43 patients achieved clinical reversal of hypercortisolism after adrenalectomy. Time to symptom resolution varied from a few weeks to up to 3 years. Most physical changes had resolved by a mean of 8 months after surgery. These conditions were not significantly different between the laparoscopy and open groups. Median length of hospital stay was shorter in the laparoscopy group （4 vs. 9 days; P 〈0.001）. Median follow-up was 48.5 months. Of the 34 （79%） patients available for follow-up, 22 （65%） had adrenocorticotropic hormone levels 〉200 ng/ml and 6 （27%） had clinical Nelson syndrome. Four patients died by 75 months after surgery. Using SF-36, 30 （88%） patients reported they felt their health status was good to excellent compared with 1 year before adrenalectomy; however, they showed significantly lower scores in all the 8 SF-36 parameters compared with the general population. No significant difference emerged in SF-36 scores between the laparoscopy and open groups. Conclusions Adrenalectomy showed high survival and clinical benefits in recurrent Cushing＇s disease patients. Despite patient-reported improvement in health after adrenalectomy, patients continue to experience poor health status compared with the general population.

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells

Background： Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 （USP8） gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor （EGFR） signaling and promote adrenocorticotropic hormone （ACTH） production. This study was to investigate whether the inhibition of USP8 activity could be a strategy/br the treatment of Cushing＇s disease （CD）. Methods： The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony tbrmation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results： Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 （ERBB2）, and Met leading to a suppression of ArT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions： Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.