Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus.

OBJECTIVES: This study aimed to evaluate the level of adrenocorticotropic hormone (ACTH) and adrenal insufficiency in patients with mucocutaneous pemphigus lesions who use oral corticosteroids. METHODS: This descriptive-analytical study was performed on 54 patients (48.44 ± 12.74 years) with mucocutaneous pemphigus in 2019. Those patients taken corticosteroids in different doses and way. At first, collected patients information including age, sex, type of pemphigus, duration of use, patient dosage, duration of corticosteroid administration, and method of administration were collected daily. Adrenal gland function was measured by evaluating ACTH levels. Data were analyzed by using Pearson correlation coefficient and t-test. RESULTS: Our study showed that 37 cases (68.5%) had normal ACTH average hormone level (7.3-63.3 mL/pg), 11 cases (20.4%) were lower levels (<7.2 mL/pg), and 6 cases (11.1%) were higher levels (63.3 > mL/pg). Wo observed no significant relationship between ACTH and duration of corticosteroids usage (p=0.207). CONCLUSIONS: Taking a maintenance dose of between 12.5 and 25 mg daily does not usually lead to adrenal insufficiency. The present study showed that the lower the daily dose of corticosteroids, the lower the likelihood of adrenal insufficiency.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.

Hormonal determinants of mammographic density and density change.

BACKGROUND: Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm2) and annual MD change (cm2/year). METHODS: This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. RESULTS: Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm2 per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm2), oesterone sulphate (+ 1.42 cm2), prolactin (+ 2.11 cm2) and SHBG (+ 4.18 cm2), and inversely associated with 11-deoxycortisol (- 1.33 cm2). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm2. Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm2 and - 1.16 cm2 lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. CONCLUSIONS: Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.

Hippocampal CCR5/RANTES Elevations in a Rodent Model of Post-Traumatic Stress Disorder: Maraviroc (a CCR5 Antagonist) Increases Corticosterone Levels and Enhances Fear Memory Consolidation.

BACKGROUND: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. AIM: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. RESULTS: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. CONCLUSION: Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session.

A clinical audit: diagnostic and epidemiological evaluation of the adrenal incidentaloma.

BACKGROUND: Audit is a clinical instrument of government characterized by a whole process of evaluation inter pares to improve medical behaviors in the clinical practice. Different endocrinopathies are underestimated in the clinical and diagnostics practice but they can be a real problem in patients admitted in the departments of Internal Medicine. The adrenal incidentaloma is an accidental discovery with an incidence equal to 4% in radiologic studies but it's rarely considereted in the internal disorders. In the departments of Internal Medicine are hospitalized each year approximately 1450,000 patients and 58,000 about them show a surrenalic lesion identified with CT or MRI as Adrenal Incidentaloma. METHODS: Through a search in the radiological archives, were reviewed all abdominal CT performed in the year 2012 in 8 departments of Internal Medicine of 8 Italian public hospitals. They also examined all medical records of these patients to value clinical management of the adrenal masses and the real incidence of the adrenal incidentaloma. RESULTS: Distribution of pathological results show an important incidence about adrenal incidentaloma in Italian patients although this pathology is represented as a rare disease and its clinical and economic burden are significant. Many questions remain unanswered as the association between duration and severity of the disease, morbidity and how the dimensions affecting it. These results need to be supported by important studies with long follow-up to realize an easy diagnosis. CONCLUSIONS: The results of this audit confirm the real incidence of this pathology in the internistic patients and the final target is to implement changes about therapeutic diagnostic pathway of the hospital patients in the internal medicine departments.

Limited significance of repeated long-term radiological and hormonal examination in nonfunctioning adrenal incidentalomas

ABSTRACT Purpose: The purposes of the present study were to evaluate growth rate of nonfunctioning adrenal incidentalomas (AIs) and their development to hormonal hypersecretion on follow-up. Materials and methods: A retrospective study was conducted from the electronic medical records. A total of 314 patients were diagnosed with adrenal tumors between 2000 and 2016. After excluding patients who had overt adrenal endocrine disorders or whose adrenal tumors were clinically diagnosed as metastatic malignancies, we investigated 108 patients with nonfunctioning AIs including characteristics, the treatment, the way of follow-up and pathology. Results: Fifteen patients received immediate adrenalectomy because of the initial tumor size or patient's preference. Pathological examination revealed malignancy in 2 patients. In the remaining 93 patients, radiological examinations were performed periodically. Tumor enlargement of ≥ 1.0cm was observed in 8.6% of the patients who were followed up as nonfunctioning AIs with a median follow-up period of 61.5 months (range: 4-192). Eleven patients underwent adrenalectomy. On the pathological examinations, all of the tumors, which showed a size increase, were diagnosed as benign tumors. Regarding the followed up patients without adrenalectomy, only 2.4% of the patients had tumor enlargement during the prolonged follow-up. Furthermore, none of the patients developed hormonal hypersecretion or clinical signs such as obesity, glucose intolerance or poorly controlled hypertension. Conclusions: Tumor enlargement of AIs did not correlate with malignancy. The value of repeat radiological and hormonal examinations may be limited in the long-term follow-up of patients whose AIs are not enlarged.

Limited significance of repeated long-term radiological and hormonal examination in nonfunctioning adrenal incidentalomas.

PURPOSE: The purposes of the present study were to evaluate growth rate of nonfunctioning adrenal incidentalomas (AIs) and their development to hormonal hypersecretion on follow-up. MATERIALS AND METHODS: A retrospective study was conducted from the electronic medical records. A total of 314 patients were diagnosed with adrenal tumors between 2000 and 2016. After excluding patients who had overt adrenal endocrine disorders or whose adrenal tumors were clinically diagnosed as metastatic malignancies, we investigated 108 patients with nonfunctioning AIs including characteristics, the treatment, the way of follow-up and pathology. RESULTS: Fifteen patients received immediate adrenalectomy because of the initial tumor size or patient's preference. Pathological examination revealed malignancy in 2 patients. In the remaining 93 patients, radiological examinations were performed periodically. Tumor enlargement of ≥ 1.0cm was observed in 8.6% of the patients who were followed up as nonfunctioning AIs with a median follow-up period of 61.5 months (range: 4-192). Eleven patients underwent adrenalectomy. On the pathological examinations, all of the tumors, which showed a size increase, were diagnosed as benign tumors. Regarding the followed up patients without adrenalectomy, only 2.4% of the patients had tumor enlargement during the prolonged follow-up. Furthermore, none of the patients developed hormonal hypersecretion or clinical signs such as obesity, glucose intolerance or poorly controlled hypertension. CONCLUSIONS: Tumor enlargement of AIs did not correlate with malignancy. The value of repeat radiological and hormonal examinations may be limited in the long-term follow-up of patients whose AIs are not enlarged.

Glucocorticoids Regulate Bone Marrow B Lymphopoiesis After Stroke.

RATIONALE: After a stroke, patients frequently experience altered systemic immunity resulting in peripheral immunosuppression and higher susceptibility to infections, which is at least partly attributed to lymphopenia. The mechanisms that profoundly change the systemic leukocyte repertoire after stroke are incompletely understood. Emerging evidence indicates that stroke alters hematopoietic output of the bone marrow. OBJECTIVE: To explore the mechanisms that lead to defects of B lymphopoiesis after ischemic stroke. METHODS AND RESULTS: We here report that ischemic stroke triggers brain-bone marrow communication via hormonal long-range signals that regulate hematopoietic B lineage decisions. Bone marrow fluorescence-activated cell sorter analyses and serial intravital microscopy indicate that transient middle cerebral artery occlusion in mice arrests B-cell development beginning at the pro-B-cell stage. This phenotype was not rescued in Myd88-/- and TLR4-/- mice with disrupted TLR (Toll-like receptor) signaling or after blockage of peripheral sympathetic nerves. Mechanistically, we identified stroke-induced glucocorticoid release as the main instigator of B lymphopoiesis defects. B-cell lineage-specific deletion of the GR (glucocorticoid receptor) in CD19-Cre loxP Nr3c1 mice attenuated lymphocytopenia after transient middle cerebral artery. In 20 patients with acute stroke, increased cortisol levels inversely correlated with blood lymphocyte numbers. CONCLUSIONS: Our data demonstrate that the hypothalamic-pituitary-adrenal axis mediates B lymphopoiesis defects after ischemic stroke.

A Novel Targeted Analysis of Peripheral Steroids by Ultra-Performance Supercritical Fluid Chromatography Hyphenated to Tandem Mass Spectrometry.

Ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS) is an alternative method for steroid analysis. Continuous development of analytical methodologies for steroid profiling is of major importance in the clinical environment to provide useful and more comprehensive data. The aim of this study was to identify and quantify a large number of endogenous steroids from the four major classes (estrogens, androgens, progestogens and corticosteroids) simultaneously within a short analytical time. This novel UPSFC-MS/MS method with electrospray in positive ionisation (ESI+) mode is robust, selective and present sufficiently high sensitivity to profile nineteen steroids in 50 µL human plasma. Under optimised conditions, nineteen different steroids were separated with high efficiency in the multiple reaction monitoring (MRM) mode. The linearity of the method was good with correlation coefficients (R2) in the range of 0.9983-0.9999 and with calibration range from 0.05-500 ng/mL in human plasma. The intraday and interday precision of the method, as RSD, was less than 15%. The accuracy of the nineteen analytes varied between 80 to 116%. Finally, the novel method was successfully applied for the determination of nineteen steroids within 5 minutes providing the possibility to use it for research as well as routine healthcare practice.

Analysis of endocrine hormone metabolism level in a Chinese patient with mucopolysaccharidosis IVA: A case report.

RATIONALE: Mucopolysaccharidosis IVA (Morquio A) is a catabolic mucopolysaccharide disorder caused by galactose-6-sulfate sulfatase deficiency. It is an autosomal recessive inherited disease. Previous reports on clinical characteristics of Morquio A mainly focused on growth retardation, skeletal deformities, and organ damage in children and adolescents, while the effects of mucopolysaccharide metabolism disorders on endocrine hormone metabolism level have not been reported. Herein, we reported the endocrine hormone metabolism in a case diagnosed as Morquio A. PATIENT CONCERNS: The patient was a 17-year-old girl with growth retardation, hearing loss, and severe skeletal dysplasia(scoliosis and chicken breast), and was evaluated to have normal nervous system function and intelligence by physicians. DIAGNOSES: She was diagnosed as Morquio A based on gene analysis, mucopolysaccharide-related enzymes and her clinical features. INTERVENTIONS: The patient didn't accepted the enzyme replacement therapy. OUTCOMES: She had a homozygous mutation of the GALNS gene. The b-glucuronidase content in the blood was reduced. The serum sodium, serum adrenocorticotropic hormone, and cortisol rhythms (8 AM) were decreased. The levels of PRA(plasma renin activity) , PAII(plasma angiotensin II), and PALD(plasma aldosterone) were elevated. Bone mineral density suggests osteoporosis. There were no abnormalities in bone metabolism indicators, growth hormone, thyroid hormone, and sex hormones. In summary, the level of endocrine hormones in patients with mucopolysaccharidosis IV changes. LESSONS: This is the report on endocrine hormone level in a patient with mucopolysaccharidosis IV in China. Due to the disease may have relatively incomplete adrenal function, which provides a basis for future understanding and diagnosis of this disease.

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas.

The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing's disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.

High-resolution multiple reaction monitoring method for quantification of steroidal hormones in plasma.

Multiple reaction monitoring (MRM) is one of the most powerful modes of analysis in liquid chromatographic tandem mass spectrometry for quantification of low-concentration metabolites in biological samples. The advances in mass spectrometry enabled the development of high-resolution multiple reaction monitoring (MRMHR ) and became suitable for the more specific analysis of target analytes. This is important for lipidomic studies and contributes in the medical and pharmaceutical fields, primarily in investigating alterations in cells or fluids relevant to various diseases. Therefore, this work proposes the development of the MRMHR method for quantification of circulating steroids. We focused on the determination of corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, and progesterone concentration in serum, by using 129sv male mice exposed to chronic unpredictable stress to validate the quantification. The method was conducted according to the ANVISA normative, adopting a coefficient of variation, as well as relative standard deviation and relative error lower than 15% in linearity, intraday and interday precision, and accuracy. For cortisol, corticosterone, and their inert metabolites (cortisone and 11-DHC), the lower limit of quantification was 3.9 ng· mL-1 , while that for progesterone and aldosterone was 7.8 and 15.6 ng· mL-1 , respectively. MRMHR analysis showed that animals submitted to stressors have 4.5 times more corticosterone in their serum than nonstressed mice. However, 11-DHC concentration does not vary significantly in response to stress for these animals. The results indicate that the method can be applied for quantification of steroids in several biological samples, such as human plasma.

Nicotine exposure suppresses hyperinsulinemia and improves endothelial dysfunction mediators independent of corticosteroids in insulin-resistant oral contraceptive-treated female rats.

Estrogen-progestin oral contraceptives (COC) or tobacco smoking has been associated with hypertension and endothelial dysfunction resulting in increased risk of cardiovascular diseases (CVD). Contrasting effects of nicotine exposure on endothelial function have been reported. The effect of non-smoking nicotine exposure on endothelial dysfunction during COC treatment remains to be fully elucidated. We therefore, sought to determine the effects of nicotine exposure during COC treatment on endothelial dysfunction mediators and circulating corticosteroids. Female Wistar rats aged 10 weeks were given (po) vehicle, nicotine (1.0 mg/kg) with or without COC steroids (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) daily for 6 weeks. Nicotine exposure caused 113.3% increase in insulinemia whereas COC treatment led to 76.9% increased insulinemia compared with control. Furthermore, COC treatment or nicotine exposure led to glucose deregulation, insulin resistance, reduced nitric oxide bioavailability, elevated plasminogen activator inhibitor-1, uric acid, oxidative stress, atherogenic dyslipidemia, and corticosteroids. However, COC + NIC treatment led to 41.2% decrease in insulemina compared with COC-treated rats. Furthermore, all other alterations were alleviated by nicotine exposure in COC-treated female rats with the exception of corticosteroids.

Testicular enlargement in a pre-pubertal boy with adrenocortical tumour.

Adrenocortical tumours are rare in children. Virilisation caused by overproduction of adrenal androgens is the most common presentation. The testes of pre-pubertal boys with this tumour are usually small or of pre-pubertal size. A 4.8-year-old boy with an adrenocortical tumour and symmetrical pubertal-sized testes is reported. The serum testosterone level was 204 nmol/L (<0.7), dehydro-epiandrosterone-sulphate 56.7 µmol/L (<1.5) and luteinising and follicle-stimulating hormones were at suppressed levels. Histology demonstrated a diffusely increased mean tubular diameter of 90 µm (the size in a 12-year-old boy) and hyperplasia of Sertoli cells. There were no Leydig cells in the interstitial area. Prolonged exposure to an extraordinarily high testosterone level could have had stimulating effects on the seminiferous tubules and Sertoli cell growth and thus contributed to testicular enlargement.

Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes.

Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15-16 week old obese and diabetic db/db mice using liquid chromatography-tandem mass spectrometry. Lean db/+ served as controls. Db/db mice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold in db/db mice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher in db/db mice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals, Cyp11b2, Cyp11b1, Cyp21a1, Hsd3b1, Cyp11a1, and StAR were all significantly increased in db/db mice compared with db/+ controls. In adipose tissue, no Cyp11b2 or Cyp11b1 transcripts were detected and no differences in Cyp21a1, Hsd3b1, Cyp11a1, or StAR expression were found between db/+ and db/db mice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in the db/db model of obesity and type 2 diabetes.

A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts.

RATIONALE: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. OBJECTIVES: To determine the value of blood analysis to identify transcriptional differences between clinically defined asthma and nonasthma groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. METHODS: Transcriptomic profiles were generated by microarray analysis of blood from 610 patients with asthma and control participants in the U-BIOPRED (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes) study. Differentially expressed genes (DEGs) were identified by analysis of variance, including covariates for RNA quality, sex, and clinical site, and Ingenuity Pathway Analysis was applied. Patient subgroups based on DEGs were created by hierarchical clustering and topological data analysis. MEASUREMENTS AND MAIN RESULTS: A total of 1,693 genes were differentially expressed between patients with severe asthma and participants without asthma. The differences from participants without asthma in the nonsmoking severe asthma and mild/moderate asthma subgroups were significantly related (r = 0.76), with a larger effect size in the severe asthma group. The majority of, but not all, differences were explained by differences in circulating immune cell populations. Pathway analysis showed an increase in chemotaxis, migration, and myeloid cell trafficking in patients with severe asthma, decreased B-lymphocyte development and hematopoietic progenitor cells, and lymphoid organ hypoplasia. Cluster analysis of DEGs led to the creation of subgroups among the patients with severe asthma who differed in molecular responses to oral corticosteroids. CONCLUSIONS: Blood gene expression differences between clinically defined subgroups of patients with asthma and individuals without asthma, as well as subgroups of patients with severe asthma defined by transcript profiles, show the value of blood analysis in stratifying patients with asthma and identifying molecular pathways for further study. Clinical trial registered with www.clinicaltrials.gov (NCT01982162).

Evaluation of potential circulating biomarkers for prediction of response to chemoradiation in patients with glioblastoma.

Surgery followed by chemoradiation and adjuvant chemotherapy is standard of care for patients with a glioblastoma (GBM). Due to its limited benefit, an upfront method to predict dismal outcome would prevent unnecessary toxic treatment. We searched for a predictive blood derived biomarker in a cohort of 55 patients with GBM. Increasing age (HR 1.03, 95 % CI 1.01-1.06), and postoperative tumor residue (HR 1.07, 95 % CI 1.02-1.15) were independently associated with unfavourable progression free survival (PFS) in these patients. Corticosteroid use before start of chemoradiaton was strongly predictive for outcome (HR 3.26, 95 % CI 1.67-6.39) with a mean PFS and OS in patients using corticosteroids of 7.3 and 14.6 months, versus 16.1 and 21.6 months in patients not using corticosteroids (p = 0.0005, p < 0.0067 respectively). Despite earlier reports, blood concentrations of YKL-40, Fetuin-a and haptoglobin were not predictive for response. In addition, serum peptide profiles, determined by MALDI-TOF mass spectroscopy, were not predictive as well. In conclusion, further biomarker discovery studies are needed to predict treatment outcome for patients with GBM in the near future.

The impact of preoperative corticosteroids on the systemic inflammatory response and postoperative complications following surgery for gastrointestinal cancer: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis examined the impact of preoperative corticosteroids on interleukin 6 (IL-6), C-reactive protein (CRP), and complications following surgery for gastrointestinal cancer. METHODS: A systematic review was performed using appropriate keywords. Random-effects meta-analysis was performed. RESULTS: 11 RCTs with 474 patients, were included. Corticosteroids were significantly associated with lower IL-6 on postoperative day 1 (mean difference -148pg/mL, 95% CI -205 to -92, p<0.001), 2 (-33pg/mL, 95% CI -58 to -8, p=0.01), and 3 (-31pg/mL, 95% CI -52 to -11, p=0.002), lower CRP on day 3 (-45mg/L, 95% CI -68 to -21, p<0.001), and 7 (-14mg/L, 95% CI -27 to -1, p=0.04), and fewer postoperative infective complications (OR 0.47, 95% CI 0.26-0.83, p=0.01). CONCLUSION: Corticosteroids were associated with reduction in the postoperative systemic inflammatory response and complications following surgery for gastrointestinal cancer.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

OBJECTIVE: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. RESULT(S): Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. CONCLUSION(S): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.