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.

Cushing＇s ulcer in traumatic brain injury

Traumatic brain injury （TBI） remains a complicated and urgent disease in our modernized cities. It becomes now a public health disease. We have got more and more patients in Neurosurgery Intensive Care Unit following motor vehicle accidents and others causes. TBI brings multiple disorders, from the primary injury to secondary injury. The body received the disturbances in the brain, in the hypothalamo-pituitary-adrenocortical （HPA） axis, in the gastric mucosa, in the immune and neuroendocrine systems. The mortality of TBI is more than 50000 deaths / year, the third of the mortality of all injuries. Cushing ulcer is one ofthe severe complications of TBI and its mortality rate is more than 50%. Many studies have improved the management of TBI and the associated complications to give patients a better outcome. Furthers studies need to be done based on the similar methodology to clarify the different steps of the HPA axis and the neuroendocrine change associated. The aim of the present review is to assess the clinical and endocrinal features of hypopituitarism and stress ulcer following TBI.

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.

Gender and magnetic resonance imaging classification-related differences in clinical and biochemical characteristics of Cushing＇s disease： a single-centre study

Background Cushing＇s disease （CD） presents a remarkable preponderance in female gender,and a significant minority of patients with CD presented with negative magnetic resonance imaging （MRI） findings.The aim of this study was to evaluate gender-related and MRI classification-related differences in clinical and biochemical characteristics of CD.Methods We retrospectively studied 169 patients with CD,comprising 132 females and 37 males,and 33 patients had no visible adenoma on MRI.Results We observed that male and MRI-positive patients presented with high adrenocorticotropic hormone （ACTH） values （P ＜0.05）.Female patients presented with higher prevalence of hirsutism and hyperpigmentation and lower prevalence of purple striae （P ＜0.05）.The prevalence of buffalo-hump and hypertension was greater in MRI-negative patients （P ＜0.05）.In addition,male patients with CD presented at a younger age compared with females （P ＜0.05）.Patients with fatigue and hypokalaemia presented significantly higher urinary-free cortisol,ACTH and cortisol levels compared with patients without these symptoms （P ＜0.05）.The prevalence of LH reduction,hyper total cholesterol （TC） and hyper low-density lipoprotein was more frequent in MRI-positive patients （P ＜0.05）.Hyper-TC levels and PRL reduction were more frequent in males （P ＜0.05）.T3,T4 and FT3 levels negatively correlated with age at diagnosis （r=-0.310,P ＜0.01; r=-0.191,P ＜0.05; r＝-0.216,P ＜0.05）.T3,T4,FT3 and FT4 levels significantly negatively correlated with 8-am plasma cortisol levels （r=-0.328,P ＜0.01; r=-0.195,P ＜0.05; r=-0.333,P ＜0.01; r＝-0.180,P ＜0.05）.Females presented higher total protein level （P ＜0.01） and lower blood urea nitrogen and serum creatinine levels （P ＜0.01）,compared with male patients.Conclusions Carefulness and caution are required in all patients with CD,because of the complexity of clinical and biochemical characteristics in CD patients of different gender and MRI classification,particularly male patients and MRI-negative patients.

Cushing＇s syndrome during pregnancy caused by adrenal cortical adenoma： a case report and literature review

Cushing＇s syndrome （CS） during pregnancy is a rare condition with Significant maternal and fetal complications. A case of CS during the third trimester of pregnancy secondary to adrenocortical adenoma was reported. Literature review revealed the disadvantages of different treatments in this period. Besides the conservative treatment, surgery is recommended for CS during the third trimester of pregnancy secondary to adrenal adenoma, if an experienced surgeon is available.

Characteristics of ectopic adrenocorticotropic hormone syndrome due to thymic carcinoid and analysis of the molecular mechanism

Ectopic adrenocorticotropic hormone （ACTH） secretion rfrom a non-pituitary tumor is a main cause of Cushing＇s syndrome, which is associated with significant morbidity and mortality. Although early studies showed that the predominant cause of ectopic Cushing＇s syndrome is small cell carcinomas of the lungs, the incidence of carcinoid, including thymic carcinoid, has increased substantially in recent surveys） This evidence suggested that the clinical syndrome of ectopic ACTH production only occurs in tumors with high proopiomelanocortin （POMC, the precursor to ACTH） transcripts generated from the start of the pituitary transcription initiation site.2

Adrenocorticotropic hormone-producing pheochromocytoma： a case report and review of the literature

Ectopic Cushing＇s syndrome caused by pheochromocytoma is rare. We reported a 15-year-old female patient who was admitted to hospital with typical Cushing＇s syndrome. She had not started menstruation. Her plasma adrenocorticotropic hormone （ACTH） and 24-hour urinary free cortisol levels were extremely high. Gonadal and progestational hormone levels were also abnormal. Abdominal computed tomography scans and enhanced scans revealed multiple irregular tumors in the right adrenal. Pelvic echogram showed an infantile uterus, while the ovaries were at an immature stage of development. Retroperitoneal laparoscopic right adrenalectomy was performed without intraoperative complications. Histology and immunohistochemistry of the tumor were consistent with pheochromocytoma. Retroperitoneal laparoscopic adrenalectomy is a safe procedure with satisfactory outcomes and allows for rapid recovery.

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.