Effects Of Glucocorticoid Treatment Research Articles

The effectiveness of glucocorticoid treatment in post-COVID-19 pulmonary involvement

RationalePersistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited.AimTo evaluate the effects of CS treatment in post-COVID respiratory syndrome patients.Patients and methodsPost-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines.ResultsThe study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894).ConclusionBetter improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.

Global analysis of the abundance of AU-rich mRNAs in response to glucocorticoid treatment

Glucocorticoids (GC) like dexamethasone (Dex) are potent anti-inflammatory agents with diverse cellular functions including the potentiation of the activity of AU-rich elements (AREs). AREs are cis-acting instability sequence elements located in the 3′UTRs of many inflammatory mediator mRNAs. Here, available RNA-seq data were used to investigate the effect of GCs on the ARE-mRNA-transcriptome. At a global scale, ARE-mRNAs had a tendency to be downregulated after GC-treatment of the A549 lung cancer cell-line, but with notable cases of upregulation. mRNA stability experiments indicated that not only the downregulated, but also the upregulated ARE-mRNAs are destabilized by Dex-treatment. Several of the most upregulated ARE-mRNAs code for anti-inflammatory mediators including the established GC targets DUSP1 and ZFP36; both code for proteins that target ARE-containing mRNAs for destruction. GCs are widely used in the treatment of COVID-19 patients; we show that ARE-mRNAs are more likely to regulate in opposite directions between Dex-treatment and SARS-CoV-2 infections compared to non-ARE mRNAs. The effect of GC treatment on ARE-mRNA abundance was also investigated in blood monocytes of COVID-19 patients. The results were heterogeneous; however, in agreement with in vitro observations, ZFP36 and DUSP1 were often amongst the most differentially expressed mRNAs. The results of this study propose a universal destabilization of ARE-mRNAs by GCs, but a diverse overall outcome in vitro likely due to induced transcription or due to the heterogeneity of COVID-19 patient’s responses in vivo.

Physiological and clinical variables identify ARDS classes and therapeutic heterogeneity to glucocorticoids: a retrospective study

ObjectiveWe aimed to identify new classes in acute respiratory distress syndrome (ARDS) using physiological and clinical variables and to explore heterogeneity in the effects of glucocorticoid therapy between classes.MethodsUsing the Medical Information Mart for Intensive Care-IV database, we identified patients with ARDS. Potential profile analysis was used to identify classes with physiological and clinical data as delineating variables. Baseline characteristics and clinical outcomes were compared between classes. The effect of glucocorticoid treatment was explored by stratifying by class and glucocorticoid treatment.ResultsFrom 2008 to 2019, 1104 patients with ARDS were enrolled in the study. The 2-class potential analysis model had the best fit (P < 0.0001), with 78% of patients falling into class 1 and 22% into class 2. Additional classes did not improve the model fit. Patients in class 2 had higher anion gap, lactate, creatinine, and glucose levels and lower residual base, blood pressure, and bicarbonate compared with class 1. In-hospital mortality and 28-day mortality were significantly higher among patients in class 2 than those in class 1 (P < 0.001). Heterogeneity of glucocorticoid treatment was observed, stratified by class and treatment, with no significant effect in class 1 (P = 0.496), increased mortality in class 2 (P = 0.001), and a significant interaction (P = 0.0381). In class 2, 28-day survival was significantly lower with glucocorticoid treatment compared with no hormone treatment (P = 0.001).ConclusionWe used clinical and physiological variables to identify two classes of non-COVID-19-associated ARDS with different baseline characteristics and clinical outcomes. The response to glucocorticoid therapy varied among different classes of patients.

The effects of glucocorticoid treatment on cardiovascular system in patients with systemic lupus erythematosus.

This study aims to assess variables concerning arterial stiffness including carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, ankle-brachial index, and the advancement of atherosclerosis development. Between October 2016 and December 2020, a total of 43 consecutive patients with systemic lupus erythematosus (SLE) (4 males, 39 females; mean age: 57±8 years; range, 42 to 65 years) were prospectively included in the study. All data were compared between the group treated with glucocorticoids and that not treated with these agents. The study group consisted of 43 patients with SLE, while 22 (51%) patients were treated with glucocorticoids. The mean duration of SLE was 12.3±5.3 years. Patients treated with glucocorticoids had lower values of ankle-brachial index compared to those who were not treated with glucocorticoids (p=0.041), although the values were within the range. A similar situation was reported for the carotid-femoral artery pulse wave velocity (p=0.032). However, carotid-radial artery pulse wave velocity was not significantly different between both groups (p=0.12). Properly selected therapy is important in the prevention of CVD.

Meta-Analysis of the Effectiveness and Safety of Glucocorticoid for the Treatment of IgA Kidney Disease

Purpose To explore the effect of glucocorticoid on immune globulin A (IgA) nephropathy by meta-analysis. Method Search the data and literature libraries of ScienceDirect, EBSCO, Wiley, PubMed, CBMdisc, and CNKI and collect the literature on the treatment of IgA nephropathy with glucocorticoids as randomized controlled trials published at home and abroad from 1995 to 2021. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by fixed-effects model. RevMan 5.0 software was used for meta-analysis of the subgroups of overall curative effect, different degree of proteinuria, different course of treatment, different creatinine level, and combined ACEI. Result ① The overall efficacy of glucocorticoid in the treatment of IgA nephropathy was better than that in the control group (P = 0.00001). ② The efficacy of glucocorticoid treatment in patients with IgA nephropathy with proteinuria greater than 1.50 g/d and less than 1.50 g/d was better than that in the control group (P < 0.01). ③ For IgA nephropathy patients with serum creatinine less than 1.50 mg/dl, the curative effect of glucocorticoid treatment was better than that of the control group (P < 0.01). ④ The effects of short-term treatment (<1 year) and long-term treatment (≥1 year) with glucocorticoid were better than those in the control group (P < 0.01). ⑤ The effect of hormone combined with ACEI drugs on IgA nephropathy was more significant (P < 0.01). Conclusion The overall efficacy of glucocorticoid in the treatment of IgA nephropathy is accurate. Hormone treatment is effective for different degrees of IgA nephropathy. Considering that there is no significant effect on the efficacy of different courses of treatment, it is suggested that the course of hormone treatment can be appropriately shortened. Hormone combined with angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria more effectively than ACEI drugs alone.

The Role of Glucocorticoids in the Treatment of ARDS: A Multicenter Retrospective Study Based on the eICU Collaborative Research Database.

Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in patients in intensive care unit (ICU). The therapeutic value of glucocorticoids (GCs) in the prognosis of ARDS remains controversial. The aim of this research is studying the impacts of GCs treatment on ARDS patients in ICU.Methods: We retrospectively studied 2,167 ARDS patients whose data were collected from the public eICU Collaborative Research Database, among which 254 patients who received glucocorticoid (GCs) treatment were 1:1 matched by propensity matching analysis (PSM). The primary outcome was ICU mortality. Every oxygenation index (PaO2/FiO2) measurement before death or ICU discharge was recorded. A joint model (JM) which combined longitudinal sub-model (mixed-effect model) and time-to-event sub-model (Cox regression model) by trajectory functions of PaO2/FiO2 was conducted to determine the effects of GCs treatment on both ICU mortality and PaO2/FiO2 level and further PaO2/FiO2's effect on event status. The marginal structural cox model (MSCM) adjusted the overall PaO2/FiO2 of patients to further validate the results.Results: The result of the survival sub-model showed that GCs treatment was significantly associated with reduced ICU mortality in ARDS patients [HR (95% CI) = 0.642 (0.453, 0.912)], demonstrating that GCs treatment was a protective factor of ICU mortality. In the longitudinal sub-model, GCs treatment was not correlated to the PaO2/FiO2. After adjusted by the JM, the HR of GCs treatment was 0.602 while GCs was still not significantly related to PaO2/FiO2 level. The JM-induced association showed that higher PaO2/FiO2 was a significant protective factor of mortality in ARDS patients and the HR was 0.991 which demonstrated that one level increase of PaO2/FiO2 level decreased 0.9% risk of ICU mortality. MSCM results also show that GCs can improve the prognosis of patients.Conclusion: Rational use of GCs can reduce the ICU mortality of ARDS patients in ICU. In addition to the use of GCs treatment, clinicians should also focus on the shifting trend of PaO2/FiO2 level to provide better conditions for patients' survival.

Endocrine Disorders in Autoimmune Rheumatological Diseases: A Focus on Thyroid Autoimmune Diseases and on the Effects of Chronic Glucocorticoid Treatment

Autoimmune rheumatological diseases’ incidence and prevalence have risen over the last decades and they are becoming increasingly important worldwide. Thyroid autoimmune diseases share with them an imbalance in the immune system that lead to a pro-inflammatory environment. Usually this is the result of a multi-factorial process. In fact, it includes not only a possible genetic predisposition, but also environmental causes like microbiota dysbiosis, diet rich in processed foods, exposure to toxicants and infections. However, many aspects are currently under study. This paper aims to examine the factors that participate in the developing of rheumatological and thyroid autoimmune diseases. Moreover, as glucocorticoids still represent a leading treatment for systemic autoimmune rheumatological diseases, our secondary aim is to summarize the main effects of glucocorticoids treatment focusing on iatrogenic Cushing’s syndrome and glucocorticoids’ withdrawal syndrome.

Effectiveness of Glucocorticoids in Acute Respiratory Distress Syndrome: An Umbrella Review

Objectives. Acute respiratory distress syndrome is a very challenging condition that is associated with high morbidity and mortality. This review was intended to evaluate evidence on the effectiveness of glucocorticoid treatment for acute respiratory distress syndrome. Method. A comprehensive search strategy was conducted on PubMed/Medline, Cochrane Library, Science Direct, and LILACS. Data extraction was carried out by two independent reviewers using a customized checklist. The quality of each systematic review was assessed by two independent reviewers using an AMSTAR tool, and the overall quality of evidence was generated with online GRADEpro GDT software for primary and secondary outcomes. Results. The umbrella review included nine systematic reviews and meta-analysis and one narrative review with 8491 participants. The methodological quality of the included studies was moderate-to-high quality. The overall quality of evidence and recommendations varied form high to very low. Conclusion. There is high-to-moderate quality evidence that early low-dose prolonged glucocorticoid therapy reduces mortality in ARDS. However, randomized controlled trials with large sample sizes to address ventilator-free days, the incidence of infection, and other glucocorticoid-associated adverse events are required as the quality of evidence for these secondary outcomes which were low to very low. Registration. This umbrella review was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42019130539).

Cytokine Profile, Apoptosis, Glucocorticoid Receptor, and P-glycoprotein Expression Before and After Megadose Methylprednisolone Treatment in Children With Acute Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease, and it has become evident that T lymphocytes play an important role in the pathogenesis of ITP. We investigated the role of T helper (Th) intracellular IL-2, IL-4, IL-6, IFN-γ, and T lymphocyte apoptosis in the pathogenesis of acute ITP and the effect of glucocorticoid treatment on cytokine profile. We investigated also P-glycoprotein (P-gp) and glucocorticoid receptor (GCR) expression as a possible mechanism for glucocorticoid resistance. The study includes 20 children with acute ITP having a platelet count <20,000/mm and 20 healthy children as a control group. Patients with acute ITP were treated with megadose methylprednisolone (MDMP) (MDMP in the dose of 30 mg/kg/d between day 1 and 3 and 20 mg/kg/d between day 4 and 7). Th intracellular IL2, IL-4, IL-6, and IFN-γ percentages, T-cell P-gp expression, T-cell and monocyte GCR expression, and T-cell apoptosis were evaluated before and after treatment in acute ITP patients and in the control group. Acute ITP patients had significantly higher Th IL-2, IL-4, IL-6, and IFN-γ percentages compared with the control group (P<0.05). Th IL-2 and IFN-γ percentages were significantly lowered with MDMP treatment (P<0.05). IFN-γ/IL-4 ratio was also lowered with the MDMP treatment (P<0.05). T-lymphocyte P-gp expression and T lymphocyte and monocyte GCR expression were all similar between acute ITP pretreatment and control groups (P>0.05). T-lymphocyte P-gp expression was higher in the posttreatment group than in the pretreatment group (P<0.05). Both T lymphocyte and monocyte GCR expression percentages were not different in the pretreatment and posttreatment groups (P>0.05). Early apoptosis in T lymphocytes was significantly lower in the pretreatment acute ITP group than in the control group (P<0.05). Necrotic apoptosis in T lymphocytes was significantly increased with MDMP treatment (P<0.05). Th1 and Th2 cytokine profile is observed in acute ITP pathogenesis, and MDMP treatment causes Th1 to Th2 cytokine profile shift and induction of T-lymphocyte apoptosis. There is a need to have a greater number of resistant cases in order to better evaluate the P-gp and GCR expression in glucocorticoid resistance in acute ITP.

Modelling the asthma phenotype: impact of cigarette smoke exposure

BackgroundAsthmatics that are exposed to inhaled pollutants such as cigarette smoke (CS) have increased symptom severity. Approximately 25% of adult asthmatics are thought to be active smokers and many sufferers, especially in the third world, are exposed to high levels of inhaled pollutants. The mechanism by which CS or other airborne pollutants alter the disease phenotype and the effectiveness of treatment in asthma is not known. The aim of this study was to determine the impact of CS exposure on the phenotype and treatment sensitivity of rodent models of allergic asthma.MethodsModels of allergic asthma were configured that mimicked aspects of the asthma phenotype and the effect of CS exposure investigated. In some experiments, treatment with gold standard asthma therapies was investigated and end-points such as airway cellular burden, late asthmatic response (LAR) and airway hyper-Reactivity (AHR) assessed.ResultsCS co-exposure caused an increase in the LAR but interestingly attenuated the AHR. The effectiveness of LABA, LAMA and glucocorticoid treatment on LAR appeared to be retained in the CS-exposed model system. The eosinophilia or lymphocyte burden was not altered by CS co-exposure, nor did CS appear to alter the effectiveness of glucocorticoid treatment. Steroids, however failed to reduce the neutrophilic inflammation in sensitized mice exposed to CS.ConclusionsThese model data have certain parallels with clinical findings in asthmatics, where CS exposure did not impact the anti-inflammatory efficacy of steroids but attenuated AHR and enhanced symptoms such as the bronchospasm associated with the LAR. These model systems may be utilised to investigate how CS and other airborne pollutants impact the asthma phenotype; providing the opportunity to identify novel targets.

Effect of glucocorticoid treatment on BAFF and APRIL expression in patients with immune thrombocytopenia (ITP)

Immune thrombocytopenic purpura (ITP) is an idiopathic bleeding disorder. B cell activating factor (BAFF) and ‘A proliferation-inducing ligand’ (APRIL) have regulatory effects on B and T cells and may represent relevant factors in the pathogenesis of ITP. Serum levels and gene expression were investigated in ITP patients. Both BAFF and APRIL serum levels were significantly elevated in active ITP. However, gene expression analysis revealed both factors to have a tendency toward downregulation. Glucocorticoid treatment significantly reduced BAFF but not APRIL serum levels, which may be mediated by differences in transcription factor binding sites. The glucocorticoid receptor binding site is present in the BAFF promotor region, but not in the APRIL promotor region. Prednisolone in combination with vitamin D3 may be effective in reducing APRIL serum levels. In conclusion, glucocorticoid treatment exerts different regulatory effects on both BAFF and APRIL, whereas antioxidant supplementation may also be beneficial in reducing serum levels.

P.122 - Effects of glucocorticoid treatment in an adult population of Duchenne muscular dystrophy patients attending the neuromuscular complex care centre: An observational study

P.122 - Effects of glucocorticoid treatment in an adult population of Duchenne muscular dystrophy patients attending the neuromuscular complex care centre: An observational study

Inhibitory effects of dexamethasone on proliferation of fibroblasts derived by idiopathic orbital inflammatory pseudotumor

Background Idiopathic orbital inflammatory pseudotumor (IOIP) is a common orbital disease, but its etiology is still unclear, so the effect of glucocorticoid treatment is unsatisfied. Objective This study was to investigate the effects of dexamethasone on orbital fibroblasts from IOIP patients and explore the action machanism. Methods Six pieces of IOIP tissues from 6 IOIP patients and 3 pieces of normal orbital connective tissues from lacrimal gland prolapse patients were obtained during the surgery in Beijing Tongren Hospital from November 2011 to January 2012.The orbital fibroblasts were cultured using explant culture method.The morphology of the cells were observed under the optical microscope, and biomarks of the cells were detected by immunochemistry.The growth and proliferation of the cells were assayed using WST-8.The expression of ICAM-1 in the cells in both the control group and the IOIP group was detected by immunochemistry.The fibroblasts were incubated in 96-well plates, and different concentrations of dexamethasone (0, 1×10-3, 1×10-4, 1×10-5 and 1×10-6 mol/L) were respectively added into the medium for 24, 48 and 72 hours, and then the proliferation of the cells was detected by WST-8 assay.The contents of ICAM-1 in different concentrations of dexamethasone groups were assayed by ELISA. Results The characteristics of the cells were similar between the control group and the IOIP group with the spindle shape and long protructions.The cells showed the positive response for vimentin and absent response for desmin, S-100, cytokeratin (CK). Compared with the control group, the growth speed of fibroblasts was fast in the IOIP group.The proliferative values of the cells (absorbancy) were gradually reduced with the increase of dexamethasone concentrations (Fconcentration=36.27, P=0.00) and the lapse of acting time (Ftime=3.69, P=0.00). In cultured cells without dexamethasone for 24, 48 and 72 hours, the mean expression levels of ICAM-1 were 0.298±0.008, 0.312±0.003 and 0.319±0.011, showing a gradually increasing trend.However, the expression of ICAM-1 was gradually reduced with the increases of concentrations and the lapse of acting time of dexamethasone (Fconcentration=75.17, P=0.00; Ftime=3.11, P=0.00). Conclusions Occurrence and development of IOIP is probably associated with the over-expression of ICAM-1 in orbital fibroblasts.Dexamethasone plays anti-inflammation and treating effects on IOIP by down-regulating the expression of ICAM-1 and inhibiting the proliferation of orbital fibroblasts. Key words: Orbital pseudotumor/drug therapy; Fibroblasts/drug effects; Glucocorticoids/pharmacology; Dexamethasone; Intercellular adhesion molecule-1; Down-regulation; Cell culture

Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment.

Although classically characterized by chronic airway inflammation with eosinophil infiltration, asthma is a complex and multifactorial condition with numerous clinical phenotypes. Epidemiological studies strongly support the link between obesity and asthma and suggest that obesity precedes and promotes asthma development, increases asthma severity, and reduces steroid responsivity. Using a house dust mite (HDM) model of airway hyperresponsiveness in C57BL/6 mice, we examined the effects of diet-induced obesity on allergic airway inflammation and its treatment with dexamethasone. When compared to lean mice treated with HDM, obese-HDM mice had reduced plasma adiponectin, an anti-inflammatory adipokine, lower eosinophil and higher macrophage infiltration into the lungs and bronchoalveolar lavage (BAL) fluid, increased expression of total, M1, and M2 macrophage markers in the lungs, and enhanced Th2 and non-Th2 cytokine expression in the lungs. While Th2-associated responses in obese-HDM mice were suppressed by systemic dexamethasone, several Th2-independent responses, including total and M1 macrophage markers in the lungs, and lung CXC-motif ligand 1 (CXCL1) levels, were not improved following dexamethasone treatment. Thus, HDM combined with obesity promotes mixed localized inflammatory responses (e.g., M1, M2, Th1, and Th2) and shifts the cellular infiltration from eosinophils to macrophages, which are less sensitive to dexamethasone regulation. Because obese asthmatics exhibit more severe symptoms, lack a predominance of Th2 biomarkers, and are predicted to experience more steroid resistance when compared to lean asthmatics, this model could be used to study blunted steroid responses in obese-HDM mice and to define the macrophages found in the lungs.

Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: A multicentric longitudinal study using the Performance of Upper Limb test

The aim of this study was to establish the possible effect of glucocorticoid treatment on upper limb function in a cohort of 91 non-ambulant DMD boys and adults of age between 11 and 26 years.All 91 were assessed using the Performance of Upper Limb test. Forty-eight were still on glucocorticoid after loss of ambulation, 25 stopped steroids at the time they lost ambulation and 18 were GC naïve or had steroids while ambulant for less than a year.At baseline the total scores ranged between 0 and 74 (mean 41.20). The mean total scores were 47.92 in the glucocorticoid group, 36 in those who stopped at loss of ambulation and 30.5 in the naïve group (p < 0.001).The 12-month changes ranged between −20 and 4 (mean −4.4). The mean changes were −3.79 in the glucocorticoid group, −5.52 in those who stopped at loss of ambulation and −4.44 in the naïve group. This was more obvious in the patients between 12 and 18 years and at shoulder and elbow levels.Our findings suggest that continuing glucocorticoids throughout teenage years and adulthood after loss of ambulation appears to have a beneficial effect on upper limb function.

Effects of Glucocorticoids Treatment on Bone BMD and TBS in Men

Effects of Glucocorticoids Treatment on Bone BMD and TBS in Men

Effects of Glucocorticoid Treatment on β- and α-Cell Mass in Japanese Adults With and Without Diabetes.

The aim of this study was 1) to clarify β-cell regenerative capacity in the face of glucocorticoid (GC)-induced insulin resistance and 2) to clarify the change in β- and α-cell mass in GC-induced diabetes in humans. We obtained the pancreases from 100 Japanese autopsy case subjects. The case subjects were classified according to whether or not they had received GC therapy before death and the presence or absence of diabetes. Fractional β-cell area (%BCA) and α-cell area (%ACA) were quantified, and the relationship with GC therapy was evaluated. As a result, in case subjects without diabetes, there was no significant difference in %BCA between case subjects with and without GC therapy (1.66 ± 1.05% vs. 1.21 ± 0.59%, P = 0.13). %ACA was also not significantly different between the two groups. In case subjects with type 2 diabetes, %BCA and %ACA were both significantly reduced compared with control subjects without diabetes; however, neither %BCA nor %ACA was significantly decreased in case subjects with GC-induced diabetes. There was a significant negative correlation between %BCA and HbA1c measured before death; however, this relationship was attenuated in case subjects with GC therapy. In conclusion, the current study suggests that β- and α-cell mass remain largely unchanged in the face of GC-induced insulin resistance in Japanese individuals, implying limited capacity of β-cell regeneration in adult humans. The absence of apparent β-cell deficit in case subjects with GC-induced diabetes suggests that GC-induced diabetes is mainly caused by insulin resistance and/or β-cell dysfunction, but not necessarily a deficit of β-cell mass.

Effect of glucocorticoid treatment on computed tomography angiography detected large-vessel inflammation in giant-cell arteritis. A prospective, longitudinal study.

Computed tomography angiography (CTA) detects signs of large-vessel vasculitis (LVV) in about 67.5% of patients with giant-cell arteritis (GCA) at the time of diagnosis and early aortic dilatation in 15%. The outcome of CTA-findings of LVV upon glucocorticoid treatment has not been prospectively evaluated.The aim of our study was to prospectively assess glucocorticoid-induced changes in CTA findings of LVV in patients with GCA.Forty biopsy-proven GCA patients evaluated by CTA at diagnosis were prospectively followed and scheduled a new CTA approximately after 1 year of treatment. Vessel wall thickening, diameter, and contrast enhancement of the aorta and its tributaries were evaluated. Results were compared to those obtained at the time of diagnosis.CTA was repeated to 35 patients after a median follow-up of 13.5 months (IQ25–75% 12.4–15.8). Arterial wall thickening was still present in 17 patients (68% of the patients who initially had LVV). The number of affected segments and wall thickness at various aortic segments significantly decreased and no patients developed new lesions, new aortic dilation or increase in previous dilation. Contrast enhancement disappeared in 15 (93.75%) of 16 patients in whom this finding could be assessed.Signs of LVV improve with treatment. While contrast enhancement resolves in the majority of patients, vessel wall thickening persists in two thirds. However, the number of affected aortic segments as well as aortic wall thickness significantly decreases. Longer follow-up is necessary to determine the clinical significance of persisting wall thickening and its relationship with relapses or subsequent development of aortic dilatation or large-vessel stenoses.

The effects of glucocorticoid treatment on cognition in patients with secondary adrenal insufficiency - results from a RCT

Introduction: A wide variety in hydrocortisone substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. So far, no studies have been performed to assess the effects of treatment regimens administered for a substantial period of time with a low physiological hydrocortisone dose in comparison to a high physiological hydrocortisone dose on cognition. Methods: This randomized, double blind cross-over study included 47 patients (mean(SD) age, 51(14) years, range 19-73) with secondary adrenal insufficiency. Patients were randomized to either group 1 (n=22), who first received a low dose during 10 weeks followed by a high dose for another 10 weeks, or group 2 (n=25), who first received a high dose followed by a low dose. All patients received a thrice-daily weight adjusted dose, with a total daily dose of 0.2-0.3 mg/kg body weight in the low dose condition and a total daily dose of 0.4-0.6 mg/kg body weight in the high dose condition. Cognitive performance of patients was measured at baseline and after each treatment period. A battery of 11 standardized cognitive tests which resulted in 37 test scores covering 4 cognitive domains (memory, attention, executive functioning and social cognition) was used. Results: Serum cortisol levels in the high dose condition were significantly higher compared to the serum cortisol levels in the low dose condition for both study periods. No differences in cognitive performance was found between the two dose regimens, except for short term memory (15 Words Test, p = 0.028, Z-score high dose (SD) = -0.03 (1.03), Z-score low dose (SD) = 0.35 (1.01), d = 0.38) and variability of reaction time in the phasic alertness task (Test of Attentional Performance, p = 0.015, Z-score high dose (SD) = -0.42 (0.79), Z-score low dose (SD) = -0.14 (0.82), d= 0.35). Conclusion Overall, no major negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of hydrocortisone in patients with secondary adrenal insufficiency when compared to a lower dose. However, minor effects of high doses of hydrocortisone on aspects of attention and short-term memory are present.

Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover

The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. 25 patients (8 M/17 F, aged 48±19yrs) recently initiating GCCT (≥7.5mg/day, ≤6months) were prospectively included. Bone turnover markers (bone formation: P1NP, osteocalcin [OC], bone ALP; bone resorption: sCTx) and Wnt antagonists (serum sclerostin and Dkk-1) were assessed in all patients (short-term and 12months after initiating GCCT). Bone mineral density (BMD) was performed to assess osteoporosis. The results were compared with 60 healthy controls. At short-term patients on GCCT showed a significant decrease in bone formation markers versus controls (P1NP: 19±9 vs. 43±16ng/mL, p<0.001; OC: 7.4±2.4 vs. 18.4±5.2ng/mL, p=0.001) and in Dkk-1 levels (24.5±20.1 vs. 36.8±13.7pmol/L, p=0.008) with similar sclerostin values (41.8±21.8 vs. 42.1±13.9pmol/L, p=0.950). Sclerostin correlated positively with GCCT doses (r=0.449, p=0.024) and lumbar BMD (r=0.424, p=0.035), and negatively with bone ALP (r=−0.398, p=0.049). A progressive decrease in Dkk-1 levels was observed at 12months, (19.1±14.9, p=0.001), whereas sclerostin increased compared to controls (48.9±11.6, p=0.045). In conclusion, the effect of GCCT on the serum levels of the Wnt signalling parameters differs depending on the antagonist evaluated. Whereas sclerostin values increased and showed a relationship with the dose and bone AP, Dkk-1 levels decreased throughout the study suggesting a counter-regulatory mechanism of this factor thereby reducing the deleterious effect of GCCT in the bone.