Adrenal Hyperplasia

The design type of this study is a prospective single center randomized controlled study, with a plan to recruit 200 patients who underwent laparoscopic adrenalectomy for the study. The intervention measures mainly include whether to indwelling drainage tubes. Prior to the start of the trial, our center had performed laparoscopic adrenalectomy on 89 patients without any obvious retroperitoneal fluid accumulation, redness, swelling, or fever, and the recovery was smooth. Step 1 of the research: Select patients who meet the criteria for laparoscopic adrenalectomy Step 2: Sign informed consent form Step 3: Randomly draw lots and divide them into two groups: no tube group (experimental group of 100 cases) and indwelling drainage tube group (control group of 100 cases) Step 4: Perform surgical plan according to grouping results Step 5: Test blood routine and ERAS related indicators 1-3 days after surgery Step 6: Follow up adrenal ultrasound at 1 month and 6 months after surgery Step 7: Follow up and analyze data Random plan Use block randomization method, using software SAS9.4 TS1M7, random seed number 2023092311 Observation items and testing time points 1. Test hemoglobin and drainage volume on 1-3 days after surgery Pain score, first time out of bed, intestinal ventilation time, adrenal ultrasound, postoperative fever, wound infection, and other indicators; During the follow-up one month after surgery, the adrenal region color ultrasound should also be tested; 3. During the follow-up examination at 6 months after surgery, ultrasound of the adrenal region should also be detected; Efficacy evaluation criteria and effectiveness evaluation methods: Whether the indwelling drainage tube has a promoting effect on the patient's rapid recovery (such as pain score, first time out of bed, intestinal ventilation time, etc.). Safety evaluation methods mainly include the subject's blood routine and vital signs.

This is a Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with atumelnant (also known as CRN04894) (an adrenocorticotropic hormone \[ACTH\] receptor antagonist) over a 10-day or 14-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome \[EAS\]). Participants will receive oral atumelnant once daily for 10 days followed by monitoring during 4 'wash-out' days, or for 14 days.

Specific Aims The purpose of the study is to perform a randomized controlled trial of women with PCOS, comparing the effectiveness of lifestyle management alone, and in combination with acupuncture or metformin treatment on whole body glucose homeostasis, with the ultimate goal to prevent the development of type 2 diabetes. Primary aim 1\. To determine the clinical effectiveness of 4 months of 1) electroacupuncture + lifestyle management and 2) metformin + lifestyle management, compared to 3) lifestyle management only, for improvement of insulin sensitivity as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels). Secondary aims 1. To evaluate changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet β-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution. 2. To determine changes in genome-wide gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood. 3. To evaluate endocrine measures including menstrual pattern and ovulation frequency, circulating hormones (sex steroids, AMH, gonadotropins), and excretion of metabolites of sex steroids in urine. 4. To determine changes in women's HRQoL, symptoms of anxiety and depression, dieting and eating patterns, and negative side-effects. 5. To evaluate the cost-effectiveness of the different treatments.

This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypotheses: (1) In normal mid- to late pubertal girls without hyperandrogenism (HA), progesterone acutely suppresses waking LH pulse frequency more than sleep-associated LH pulse frequency; and (2) compared to normal mid- to late pubertal girls without HA, acute progesterone suppression of waking LH pulse frequency is impaired in mid- to late pubertal girls with HA. Studies will be performed in mid- to late pubertal girls (at least Tanner breast stage 3 but no more than 2 years postmenarcheal). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Immediately before and during the first CRU admission, either oral micronized progesterone (0.8 mg/kg/dose) or placebo (randomized) will be given at 0700, 1500, 2300, and 0700 h. During the CRU admission, blood will be obtained every 10 minutes through an indwelling iv catheter from 1800 to 1200 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo will exchanged for progesterone or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) Results in pubertal girls without HA were recently published (Kim et al, J Clin Endocrinol Metab 2018;103:1112-1121). Data from girls with HA will be compared to recently-published results in girls without HA. Mean LH pulse frequency while awake will be analyzed via a hierarchical linear mixed model (HLMM). HA status (HA vs. non-HA), sleep status (wake vs. sleep), and treatment (progesterone vs. placebo) will represent fixed-effects, along with all associated interactions. Random effects will be used to account for hierarchical variance-covariance structure of the crossover study design. With regard to hypothesis testing, the association between HA status and wake LH pulse frequency will be evaluated via linear contrasts of HLMM least squares pulse frequency means. The differential impact of exogenous progesterone on wake LH pulse frequency in pubertal girls with and without HA (primary analysis) will be evaluated via the same testing method. Using published and preliminary data, we determined that, if 16 pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.2 pulse/hour differential effect of P4 on wake LH pulse frequency between the HA and the non-HA groups with a two-sided false positive rejection rate of no more than 0.05.

The pathogenesis of adrenal tumors is still not fully elucidated and the treatment options for malignant tumors are poor. The current study investigates different aspects of the pathogenesis of adrenal tumors and evaluates different therapeutic options in patients with adrenocortical carcinoma.

The aim of the study is to validate the B-COMPASS in real-life settings. Overall, the purpose is to provide evidence 1) to validate the B-COMPASS (primary purpose), and 2) to demonstrate the effectiveness and implementability of the B-COMPASS (secondary purpose). The project will carry out the final iterative steps of refining the model, guided by the validation studies that have been conducted. This process will be based on evaluating the performance of the generic model across six selected therapeutic areas (cardiovascular, endocrinology, immunology, neurology, oncology and rare diseases). Study participants (patients and HCPs) will be recruited (at least) from Italy, Portugal, Norway, Spain, The Netherlands, and Germany, and the validation will evaluate the capacity to attend to a variety of needs and challenges for adherence to treatment. Overall, the study has 8 Scientific Questions (SQs), where SQ 1-4 address the validity of the B-COMPASS (primary purpose) and SQ 5-8 address the effectiveness and implementability of the B-COMPASS (secondary purpose). The SQs are: SQ 1 How accurately does the B-COMPASS predict the relative adherence to treatment for patients? SQ 2 How valid are the B-COMPASS groupings? SQ 3 How accurately are the patient support needs identified by the B-COMPASS? SQ 4 How reliable is the B-COMPASS over time? SQ 5 To what extent does the use of the B-COMPASS affect patient adherence to treatment? SQ 6 How do the patients perceive the received engagement with HCPs/Research Leads based on the B-COMPASS? SQ 7 How do HCPs/Research Leads perceive the B-COMPASS? SQ 8 How does the B-COMPASS impact the cost-effectiveness of healthcare utilisation?

All the woman who will recruited in the study will undergo OGTT. At 0, 60, and 120 min of glucose load the investigators will measure: a) glucose and insulin, b) pulse wave velocity (PWV) c) augmentation index (Aix) and d) perfused boundary region of sublingual microvessels (high PBR values represent reduced glycocalyx thickness). At 0 and 120 min of glucose load, the investigators will assess: a) coronary flow reserve (CFR) using Doppler echocardiography, b) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers and global LS (GLS) c) peak twisting (pTw), untwisting velocity (pUtwVel) by speckle tracking echocardiography d) flow mediated dilation (FMD) of the brachial artery, e) Carotid intima-media thickness. Matsuda index, insulin sensitivity index (ISI) and HOMA index will be also measured. The levels of Testosterone (Τesto), Sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-s), Prolactin (PRL), 17-hydroxyprogesterone (17-OH-PRG) ,Androstenedione (Δ4) and Metalloproteinase 9 will be also assessed. After six months of treatment intervention, the patient will undergo the previously described measurements. Primary Endpoints include the change in GLS, PWV, and PBR during OGTT and six months after treatment intervention. Secondary Endpoints include the change in CFR and FMD during OGTT and six months after treatment intervention.

Introduction According to data from the World Health Organization, cardiovascular disease is the leading cause of death worldwide. It is estimated that in 2015, 18 million people died from this cause, representing 31% of all deaths recorded globally. The majority of these deaths (7.4 million) were due to coronary heart disease. Additionally, cardiovascular disease represents the highest burden of disease, defined by disability-adjusted life years (DALY), with 4,800 DALY per 100,000 inhabitants. From a clinical perspective, the topic that concerns us within cardiovascular disease is acute coronary syndrome (ACS), which refers to a group of signs and symptoms compatible with acute myocardial ischemia. In this context, for decades, to optimize diagnosis and provide timely treatment, ACS has been subclassified into acute myocardial infarction with (STEMI) and without ST-segment elevation (NSTEMI) and unstable angina (UA). Among the broad spectrum of ACS, the least severe form is UA, where symptoms suggest myocardial ischemia but there is no biochemical evidence of myocardial infarction. At the other extreme is acute myocardial infarction, whose clinical definition is based on the presence of acute myocardial damage detected by the elevation of cardiac biomarkers (troponin) in the context of evidence of acute myocardial ischemia. It is classified into five types, with type 1, caused by atherothrombotic coronary disease, being the focus of this study. This type is often precipitated by the rupture or erosion of an atherosclerotic plaque. Background and Rationale Years of exhaustive clinical research have resulted in therapies that reduced mortality and complication rates of ACS, ranging from the creation of the Coronary Care Unit, anticoagulation therapies, beta-blockers, renin-angiotensin-aldosterone system inhibitors, antiplatelet therapies, to reperfusion, whether mechanical or pharmacological. However, in recent years, we have not been able to make a qualitative leap in the pathophysiological approach to coronary disease to create new paradigms in therapeutics. Thus, it is imperative to seek new horizons, new pathophysiological hypotheses, addressing topics such as inflammation, immune response, immunothrombosis, and stress response in the context of ACS. It is undeniable that inflammation and stress are risk factors for developing ACS. Additionally, ACS triggers both an acute inflammatory response and a stress response, with cortisol being one of the main effectors of the latter, possessing anti-inflammatory effects. However, we currently lack a deep understanding of the mechanisms governing this interesting dialogue between inflammation and stress in the context of ACS. Some authors have described that a higher degree of inflammation is associated with worse outcomes in ACS patients. Recently, we described that this poor outcome is related to plasma cortisol levels. We know that stress has complex effects on the immune system, influencing both innate and adaptive immunity. Glucocorticoids and catecholamines, in the acute phase of the stress response, can influence the trafficking and/or function of leukocytes (neutrophil demargination), induce a systemic shift from a TH1 (cellular immunity) to a TH2 (humoral immunity) response. Additionally, acute stress can increase circulating pro-inflammatory cytokine levels such as IL-6, IL-1b, and C-reactive protein (CRP). This bidirectional interaction between stress response effectors and the immune system is evident as pro-inflammatory cytokines stimulate the stress system at multiple levels, including the central and peripheral nervous systems, hypothalamus, pituitary, and adrenal glands, increasing glucocorticoid levels. The literature extensively supports the utility of leukocyte indices in ACS. One of the most widely used is the neutrophil-to-lymphocyte ratio (NLR), which has demonstrated its association with the severity of clinical presentation and coronary lesions, as well as its ability to predict events during hospitalization and after discharge. However, we lack studies explaining the mechanisms underlying this index with certainty. We know that exogenous glucocorticoids can cause transient neutrophilia by recruiting the marginal pool and lymphopenia through apoptosis. Recently, other mechanisms have been proposed that could explain the lymphopenia associated with severe acute stress events linked to transient immunodepression, although evidence is scarce. Similarly, although limited, there is interesting information regarding eosinopenia as a prognostic marker in severe acute diseases, with studies published on its utility in stroke, sepsis, and one in ACS. We know that exogenous glucocorticoid administration can induce eosinopenia, and apoptosis is proposed as one of the mechanisms causing it, which is why corticosteroids have been part of the first-line treatment for autoimmune and allergic diseases where these cells play a predominant role. Currently, we lack human studies demonstrating the association of these cellular immunity components' behavior with stress and inflammation response markers in the context of ACS. Research Objectives and Hypotheses Hypothesis: In ACS, there is an increase in cortisol levels (as an expression of the stress response) and CRP (as an expression of the inflammatory response) associated with changes in cellular immunity components, which are predictors of clinical events. Objectives: Describe the leukocyte, neutrophil, lymphocyte, and eosinophil counts and their association with the clinical presentation of ACS patients. Describe the leukocyte, neutrophil, lymphocyte, and eosinophil counts and their association with the presence of heart failure in ACS patients. Describe the leukocyte, neutrophil, lymphocyte, and eosinophil counts and their association with clinical events during hospitalization in ACS patients. Describe the leukocyte, neutrophil, lymphocyte, and eosinophil counts and their association with clinical events post-discharge in ACS patients. Correlate the leukocyte, neutrophil, lymphocyte, and eosinophil counts with maximum levels of high-sensitivity troponin, CPK, and CPK-MB as expressions of tissue damage in ACS. Correlate the leukocyte, neutrophil, lymphocyte, and eosinophil counts with total serum cortisol levels as a marker of stress response in ACS. Correlate the leukocyte, neutrophil, lymphocyte, and eosinophil counts with CRP levels as a marker of inflammation in ACS. Methodology A prospective, observational, analytical, single-center study will be conducted on successive patients with acute coronary syndrome, with a follow-up of 6 months. For two years, all eligible patients admitted with a diagnosis of ACS to the Coronary Unit of Hospital de Clínicas José de San Martín in Buenos Aires will be successively registered. All included patients will undergo a baseline electrocardiogram and physical examination at admission, and appropriate therapeutic measures will be implemented according to their condition, as indicated by the treating physician, without influence from study protocol inclusion. Demographic and clinical data will be obtained from the medical history. Additionally, a blood sample will be taken at admission for the measurement of ultra-sensitive CRP and cortisol. During hospitalization, the evolution curve of necrosis markers (troponin, CPK, and CPK-MB) will be evaluated from admission until the peak is confirmed and the decline begins. Total leukocyte, lymphocyte, and eosinophil counts will be recorded at patient admission. Post-discharge, a telephone follow-up will be conducted for 6 months. Sample Size Calculation: Considering an event incidence of 20% and an alpha error of 0.5 and beta error of 0.5, the number of patients to be included should be equal to or greater than 150. For statistical analysis, categorical variables will be presented as frequencies, and continuous variables as mean with standard deviation if normally distributed, or median with interquartile ranges if not. Pearson's chi-square or Fisher's exact test and Student's t-test or Wilcoxon rank-sum test will be used for comparisons depending on whether variables are categorical or continuous and normally distributed or not. Correlations will be assessed using Pearson or Spearman coefficients. Intraobserver and interobserver variability will be analyzed using the intraclass correlation coefficient. Statistical significance will be set at a two-tailed p-value less than 0.05. All calculations will be performed using R version 3.5.1.

In order to meet all the challenges in the diagnosis and treatment of adrenal diseases in China, CASE was founded in 2020. With advanced medical equipment and Internet of Things (IoT) technology, CASE is committed to creating an online and offline integrated solution for adrenal disease, and for the entire spectrum of adrenal disease, to achieve a more convenient and precise model of care for patients, aiming to establish a platform with diagnosis and treatment of adrenal disease and their long-term follow-up. It allows the application and evaluation of treatment strategies at these centers.

The purpose of this study is to follow participants with Cushing's syndrome during the course of their routine care and to form a data registry to study long term participant outcomes.