scholarly journals Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

2022 ◽  
Vol 23 (2) ◽  
pp. 673
Author(s):  
Vittoria Favero ◽  
Arianna Cremaschi ◽  
Chiara Parazzoli ◽  
Alberto Falchetti ◽  
Agostino Gaudio ◽  
...  
Keyword(s):  
Subclinical Atherosclerosis ◽  
Pituitary Tumors ◽  
Bone Fragility ◽  
Clinical Effects ◽  
Cortisol Secretion ◽  
Peripheral Tissues ◽  
Dehydrogenase Enzyme ◽  
Skin Fragility ◽  
Clinical Consequences ◽  
Peripheral Activation

Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation).

scholarly journals STMO-06 SMART CYBER OPERATING THEATER REALIZED BY INTERNET OF THINGS - RESULTS OF CLINICAL STUDY FOR 56 CASES

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
Muragaki Yoshihiro ◽  
Jun Okamoto ◽  
Taiichi Saito ◽  
Satoshi Usui ◽  
Ushio Yonezawa ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Removal Rate ◽  
Tumor Resection ◽  
Pituitary Tumors ◽  
Residual Tumor ◽  
Clinical Results ◽  
Digital Data ◽  
Clinical Effects ◽  
Operating Theater ◽  
First Case

Abstract PURPOSE Unlike conventional operating rooms that provide a sterilized space, we have developed a Smart Cyber Operating Theater (SCOT) in which the room itself performs treatment as a single medical device. We report the clinical results of 3 types of SCOT. METHODS Basic SCOT packaged with intraoperative MRI (0.4Tesla) was introduced in Hiroshima University in 2016. Standard SCOT networked with middleware OPeLiNK was introduced to Shinshu University in 2018, and Hyper SCOT introduced to Tokyo Women’s Medical University in 2019. RESULTS The average of all 56 patients was 44 years old. There were 38 brain tumors (68%), 11 functional diseases (19%), and 7 orthopedic diseases (13%). Basic SCOT is used for 41 cases (/56; 73%) with 22 gliomas, 10 epilepsies, 7 bone tumors, and 2 benign brain tumors. Standard SCOT with 20 networked devices is used for 14 cases (/56; 25%) with 6 gliomas including brain stem and thalamus, 6 pituitary tumors and 2 benign brain tumors. The strategy desk can display a variety of digital data synchronized in time, and the review and comment functions also operate. It is useful for remote advice through mutual communication via strategy desk. Hyper SCOT was used in February 2019 for the first case (1/56 cases; 2%). MRI images were taken with an average of 1.3 shots with good image quality. For 46/56 neoplastic lesions (82%), additional removal of residual tumor was performed in 31/46 cases (67%), and 26/46 cases (57%) were totally removed, with an average removal rate of 89.2%. There was no reoperation (0%) within 1 month in all cases. CONCLUSIONS Three types of SCOT contributed to planned surgical outcome including maximal tumor resection without serious related complications. We will proceed with verification of clinical effects, and develop robotized devices, and utilize AI for strategy desk at Hyper SCOT.

scholarly journals Vitamin A metabolic aspects and alcoholic liver disease

2006 ◽  
Vol 19 (5) ◽  
pp. 601-610
Author(s):  
Tatiana Pereira de Paula ◽  
Wilza Arantes Ferreira Peres ◽  
Rejane Andréa Ramalho ◽  
Henrique Sérgio Moraes Coelho
Keyword(s):  
Retinoic Acid ◽  
Liver Disease ◽  
Vitamin A ◽  
Alcoholic Liver Disease ◽  
Vitamin A Deficiency ◽  
Scientific Evidence ◽  
Acid Synthesis ◽  
Clinical Effects ◽  
Chronic Alcoholic ◽  
Peripheral Tissues

The liver is a strategic organ in the metabolism of macro and micronutrients; when its functioning is compromised, it may cause some change in the nutritional status of vitamin A. The purpose of this article is to review scientific evidence in literature on the liver metabolism of vitamin A, the role of ethanol and retinol interactions on hepatic morphology, besides the alterations in the metabolism of this vitamin in alcoholic liver disease. Data were collected from Medline database. The liver is the main organ responsible for the storage, metabolism and distribution of vitamin A to peripheral tissues. This organ uses retinol for its normal functioning such as cell proliferation and differentiation. This way, vitamin A deficiency seems to alter liver morphology. Patients with alcoholic liver disease have been found to have low hepatic levels of retinol in all stages of their disease. In alcoholic liver disease, vitamin A deficiency may result from decreased ingestion or absorption, reduction in retinoic acid synthesis or increased degradation. Long-term alcohol intake results in reduced levels of retinoic acid, which may promote the development of liver tumor. So, in chronic alcoholic subjects, vitamin A status needs to be closely monitored to avoid its deficiency and clinical effects, however its supplementation must be done with caution since the usual dose may be toxic for those who consume ethanol.

scholarly journals Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ding Nie ◽  
Yimeng Xue ◽  
Qiuyue Fang ◽  
Jianhua Cheng ◽  
Bin Li ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Antitumor Immunity ◽  
Treatment Options ◽  
Cell Activity ◽  
Pituitary Tumors ◽  
Immune Checkpoints ◽  
Intracranial Tumors ◽  
Peripheral Tissues ◽  
Effective Strategies ◽  
Immune Injury

Pituitary tumors are the third most common intracranial tumors in adults. Treatment of refractory pituitary tumors is known to be difficult due to limited treatment options. As a promising therapeutic method, tumor immunotherapy has been applied in the treatment of many tumors, including pituitary tumors. Immune checkpoint blocking is one of the effective strategies to activate antitumor immunity. Immune checkpoints prevent tissue damage by regulating the immune response of peripheral tissues and participate in the maintenance of a normal immune environment. In the presence of a tumor, inhibition of T cell activity by tumor cells binding to immune checkpoints and their ligands is an important mechanism for tumor cells to escape immune injury. In this review, we summarize the latest findings of immune checkpoints and their potential as immunotherapeutic targets for pituitary tumors.

Clinical and Analytical Impact of Moving from Jaffe to Enzymatic Serum Creatinine Methodology

2020 ◽  
Vol 5 (4) ◽  
pp. 631-642
Author(s):  
Neil R Syme ◽  
Kathryn Stevens ◽  
Catherine Stirling ◽  
Donald C McMillan ◽  
Dinesh Talwar
Keyword(s):  
Serum Creatinine ◽  
Significant Proportion ◽  
Clinical Effects ◽  
Serum Samples ◽  
Clinical Consequences ◽  
Paired Analysis ◽  
Creatinine Measurement ◽  
Abbott Architect ◽  
Accurate Quantification ◽  
Good Agreement

Abstract Background Identification and monitoring of chronic kidney disease (CKD) requires accurate quantification of serum creatinine. The poor specificity of Jaffe creatinine methods is well documented, and guidelines recommend enzymatic methodology. We describe our experience of moving from Jaffe to enzymatic creatinine methodology. We present comparison of >5000 paired Jaffe and enzymatic creatinine results, examine interferences, and attempt to assess clinical consequences of changing methodology. Methods Overall, 5303 serum samples received for routine creatinine measurement were analyzed using Jaffe and enzymatic methods with an Abbott Architect autoanalyzer. Associated results for glucose, total bilirubin, triglycerides, total protein, and hemolytic, icteric, and lipemic indexes were extracted from the laboratory database. CKD staging was estimated for each sample to assess potential clinical effects. Results The methods correlated well (r = 0.996) and showed good agreement (Passing-Bablok fit, y = 0.935x + 0.074). Paired analysis, however, showed significant differences (P < 0.001), and approximately 20% of results differed by more than ±10%. Multivariate analysis demonstrated independent associations between difference in creatinine results, glucose (P < 0.0001), and hemolytic index (P = 0.009). Glucose demonstrated positive interference in the Jaffe method, and hemolysis produced negative interference in the enzymatic method. Little or no association was observed with other analytes. CKD staging differed in 4% of samples. Conclusions Differences between Jaffe and enzymatic serum creatinine results exceed the recommended 5% target for a significant proportion of samples, particularly at concentrations <1.13 mg/dL (100 µmol/L). Both glucose and hemolysis contribute to the variance in results. Although the clinical impact of these differences seems small, laboratories should continue moving toward enzymatic creatinine estimation to ensure the best estimate of renal function.

Clinical Characteristics and Follow-Up Results of Adrenal Incidentaloma

2020 ◽  
Author(s):  
Nusret Yilmaz ◽  
Esin Avsar ◽  
Gokhan Tazegul ◽  
Ramazan Sari ◽  
Hasan Altunbas ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adrenocortical Carcinoma ◽  
Clinical Characteristics ◽  
Adrenal Incidentaloma ◽  
Cortisol Secretion ◽  
Clinical Consequences ◽  
Mass Size ◽  
Autonomous Cortisol Secretion ◽  
Radiological Changes

AbstractIt is recommended that adrenal incidentaloma patients should be monitored for radiological changes, increase in size and new functionality that may occur in the future, even if they are benign and nonfunctional at the initial evaluation. Our aim is to evaluate the key clinical characteristics of adrenal incidentaloma patients focusing on changes during follow-up and associated clinical outcomes. A total of 755 patients (median age: 56 years), with an adrenal incidentaloma > 1 cm and underwent functionality tests, were included in the study. Clinical characteristics, functionality status and follow-up durations were recorded. During the course of follow-up, any changes in size and development of new functionality, and clinical consequences thereof were evaluated. In 71.8% of patients, incidentalomas were non-functional. Most frequent functionality (15.8%, n=119) was subclinical hypercortisolemia (SH) [10.9% (n=82) possible autonomous cortisol secretion (PACS) and 4.9% (n=37) autonomous cortisol secretion (ACS)] of all incidentalomas. Frequencies of Cushing’s syndrome (CS), pheochromacytoma and primary hyperaldosteronism were 4.9% (n=37), 3.8% (n=29) and 3.7% (n=28), respectively. Adrenocortical carcinoma frequency was 1.5% (n=11). Of 755 patients, 43% (n=325) were followed up regularly more than 6 months. Median follow-up duration was 24 months (6–120). A total of 17 (5.2%) patients, which had non-functional incidentalomas at baseline had developed new functionality during follow-up, of which 15 (4.6%) were SH [13 patients (4%) PACS and 2 patients (0.6%) ACS] and 2 (0.6%) were CS. During follow-up, 24% (n=78) of the patients had an increase in mass size between 5–9 mm, while 11.7% (n=38) of the patients had an increase of ≥10 mm. During follow-up, 4% (n=13) of the patients developed a new lesion with a diameter ≥10 mm on the opposite side. In patients with a follow-up duration of more than 2 years, frequencies of size increase and new lesion emerging at the opposite adrenal gland were higher. 14 patients (4.3% of the patients with regular follow-up) underwent surgery due to increase in size or development of new functionality during follow-up. Our study demonstrated that a necessity for surgery may arise due to increase in size and development of functionality during follow-up period in adrenal incidentaloma patients, and thus continuing patient follow-up, even with wider intervals, will be appropriate.

scholarly journals SUN-614 Prediction of Hypertension, Diabetes and Fractures in Eucortisolemic Women by Measuring Parameters of Cortisol Milieu

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Iacopo Chiodini ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
Agostino Gaudio ◽  
Cristina Eller-Vainicher ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Fragility Fractures ◽  
Urinary Free Cortisol ◽  
Sensitivity Index ◽  
Cortisol Secretion ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Free Cortisol ◽  
Peripheral Activation

Abstract Purpose. Cortisol secretion, peripheral activation and sensitivity seem to be associated with hypertension (HY), type-2 diabetes (T2D) and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cut-off(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence of HY, T2D and FX (comorbidities). Methods. In 206 postmenopausal females (157 with ≥1 comorbidities and 49 without any), we assessed the ratio between 24-hour urinary free cortisol and cortisone (R-UFF/UFE, cortisol activation index), cortisol after 1mg-overnight-dexamethasone (F-1mgDST, cortisol secretion index), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP, cortisol sensitivity index). Results. The cut-offs for F-1mgDST and R-UFF/UFE set at 0.9 μg/dL (Area Under the Curve, AUC 0.634±0.43, p=0.005) and 0.17 (AUC 0.624±0.5, p=0.017) respectively, predicted the presence of ≥1 comorbidities. The presence of F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 showed 82.1% specificity for predicting the presence of ≥1 comorbidities, while the simultaneous presence of F-1mgDST ≤0.9 μg/dL and R-UFF/UFE ≤0.17 showed 88% sensitivity for predicting the absence of comorbidities. The F-1mgDST >0.9 μg/dL or R-UFF/UFE >0.17 was associated with 2.8 and 2.1 fold increased risk of having ≥1 comorbidities, respectively. The F-1mgDST ≤0.9 μg/dL plus R-UFF/UFE ≤0.17 or F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 was associated with 2.8 fold reduced or 4.9 fold increased risk of having ≥1 comorbidities regardless of age, BMI and N363S-SNP. Conclusions. F-1mgDST >0.9 μg/dL and R-UFF/UFE >0.17 may be used for predicting the presence of ≥1 among HY, T2D and fragility FX.

scholarly journals The physiological basis of complementary and alternative medicines for polycystic ovary syndrome

2011 ◽  
Vol 301 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
Nazia Raja-Khan ◽  
Elisabet Stener-Victorin ◽  
XiaoKe Wu ◽  
Richard S. Legro
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Subclinical Atherosclerosis ◽  
Clinical Effects ◽  
Physiological Effects ◽  
Ovary Syndrome ◽  
Physiological Basis ◽  
Autonomic Nervous ◽  
Positive Effects ◽  
Complementary And Alternative

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitary-adrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled. Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of CAM treatments for PCOS.

scholarly journals Cortisol as a Biomarker of Mental Disorder Severity

2021 ◽  
Vol 10 (21) ◽  
pp. 5204
Author(s):  
Ewelina Dziurkowska ◽  
Marek Wesolowski
Keyword(s):  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Biological Marker ◽  
Cortisol Secretion ◽  
Peripheral Tissues ◽  
Current State ◽  
The Face ◽  
The Central Nervous System ◽  
Cortisol Levels ◽  
Healthy Participants

Cortisol—the most important steroid hormone with a significant effect on body metabolism—strongly affects peripheral tissues and the central nervous system. Fluctuations in cortisol secretion often accompany psychiatric disorders, and normalization of its levels correlates with improvement in the patient’s health. This indicates that cortisol may be useful as a biological marker that can help determine the likelihood of mental illness, its impending onset, and the severity of symptoms, which is especially important in the face of the increasing prevalence of mental disorders, including those associated with social isolation and anxiety during the COVID-19 pandemic. This publication reviews recent reports on cortisol levels in healthy participants and shows the current state of knowledge on changes in the levels of this hormone in people at risk for depression, bipolar disorder, and psychosis. It shows how people with psychiatric disorders react to stressful situations and how the applied therapies affect cortisol secretion. The influence of antidepressants and antipsychotics on cortisol levels in healthy people and those with mental disorders is also described. Finally, it reviews publications on the patterns of cortisol secretion in patients in remission.

The Therapeutic Potential of Novel Kappa Opioid Receptor-based Treatments

2020 ◽  
Vol 27 (12) ◽  
pp. 2012-2020 ◽  
Author(s):  
Sebastiano Mercadante ◽  
Patrizia Romualdi
Keyword(s):  
Chronic Pain ◽  
Opioid Receptor ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Experimental Studies ◽  
Kappa Opioid Receptor ◽  
Clinical Effects ◽  
Kappa Opioid ◽  
Peripheral Tissues

Introduction: Similarly to the μ opioid receptor, kappa opioid receptor (KOR), is present either in the central nervous system or in peripheral tissues. In the last years, several molecules, able to interact with KOR, have been the focus of basic research for their therapeutic potential in the field of chronic pain, as well as in depression, autoimmune disorders and neurological diseases. Discussion: The role of KOR system and the consequent clinical effects derived by its activation or inhibition are discussed. Their potential therapeutic utilization in conditions of stress and drug relapse, besides chronic pain, is presented here, including the possible use of KORagonists in drug addiction. Moreover, the potential role of KOR-antagonists, KOR agonistantagonists and peripheral KOR agonists is proposed. Conclusion: Other than pain, KORs have a role in regulating reward and mood. Due to its location, KORs seem to mediate interactions between psychiatric disorders, addiction and depression. Experimental studies in animal models have identified brain mechanisms that may contribute to clarify specific pathophysiological processes.

Immunogenicity of bone morphogenetic proteins

2009 ◽  
Vol 10 (5) ◽  
pp. 443-451 ◽  
Author(s):  
Chang Ju Hwang ◽  
Alexander R. Vaccaro ◽  
James P. Lawrence ◽  
Joseph Hong ◽  
Huub Schellekens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bone Morphogenetic Proteins ◽  
Antibody Formation ◽  
Binding Assay ◽  
Antibody Detection ◽  
Clinical Effects ◽  
Human Proteins ◽  
Clinical Consequences ◽  
Safety Parameter ◽  
Osteogenic Protein

Object The object of this paper is to review the immunogenicity of bone morphogenetic proteins (BMPs) and to compare the results of the immunogenicity characterization and clinical consequences between recombinant human (rh)BMP-2 and recombinant human osteogenic protein-1 (rhOP-1/BMP-7). Methods The immunogenicity of therapeutic proteins and its clinical effects were reviewed. The characteristics of BMPs were also described in terms of immunogenicity. The methods and results of antibody detection in various clinical trials of rhBMP-2 and rhOP-1 were compared, including the most recent studies using a systematic characterization strategy with both a binding assay and bioassay. Results Similar to all recombinant human proteins, rhBMPs induce immune responses in a select subgroup of patients. Adverse effects from this response in these patients, however, have not been reported with antibody formation to either rhBMP-2 or rhOP-1. Overall, the incidence of antibody formation was slightly higher in rhOP-1 trials than in rhBMP-2 trials. Conclusions Although they occur in a subgroup of patients, the immune responses against rhBMPs have no correlation with any clinical outcome or safety parameter. Clinicians, however, must be aware of the potential complications caused by the immunogenicity of BMPs until more studies clearly elucidate their safety.

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