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PubMed1972

Circadian corticosteroid periodicity: critical period for abolition by neonatal injection of corticosteroid.

Circadian variation of corticosteroid concentrations in rat plasma is suppressed if corticosteroids are administered between days 2 to 4 of neonatal life, but not if they are given between days 12 to 14 of neonatal life. This indicates a critical period for the effect of corticosteroid administration on the central nervous system pathways regulating such periodicity. Circadian periodicity of corticosteroids is not affected by neonatal administration of testosterone or reserpine.

Adrenal Cortex Hormones↗
PubMed2000

An observation study evaluating the efficacy of tazarotene plus corticosteroid in treating plaque psoriasis in patients switched from treatment with calcipotriene +/- corticosteroid.

The results of a multicenter, open-label observation study evaluating the use of tazarotene in 1393 patients being treated for plaque psoriasis have been reported recently. The analysis of data from a subset of 166 patients who were switched from calcipotriene therapy, with or without a topical corticosteroid, to receive tazarotene plus a corticosteroid is reported here. This subset of 166 patients showed substantial additional improvements in efficacy and patient satisfaction over and above those already achieved with calcipotriene +/- corticosteroid treatment. The mean scores for overall severity of plaque psoriasis, plaque elevation, scaling, pruritus, and overall discomfort were reduced by 35%, 41%, 44%, 45%, and 40%, respectively, compared with baseline levels at the time of switching therapy. The severity of each of these parameters was reduced from mild-to-moderate at baseline to trace-to-mild after a mean of 10 weeks' treatment with tazarotene plus a corticosteroid.

Administration, Topical↗
PubMedDate not supplied

[Role of corticosteroids in the regulation of the sex-differentiated level of corticosteroid-binding globulin in rats].

A study was made of the role of the adrenal cortex in the formation and modulation of the level of corticosteroid-binding globulin (CBG) in the serum of male and female rats. Corticosteroids were shown to be potent negative regulators of a CBG level in rats, the level of this protein being more sensitive to the action of these hormones in male rats than in females. Adrenalectomy in mature as well as in prepubertal rats did not level down sex differences in the level of CBG. A study of possible interdependent influence of corticosteroids and sex hormones on the level of CBG has shown that adrenocortical hormones produce an independent direct effect of the level of CBG. Producing a negative effect on the level of CBG, corticosteroids are involved in the modulation of sex dimorphism of the level of this protein in rats, enhancing sex differentiation of the CBG level in males and weakening it in female rats.

Adrenal Cortex Hormones↗
PubMed1977

[Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)].

Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication.

Adrenal Cortex Hormones↗
PubMed2005

A prospective, randomized, multicenter, double-blind study of early corticosteroid cessation versus long-term maintenance of corticosteroid therapy with tacrolimus and mycophenolate mofetil in primary renal transplant recipients: one year report.

This report summarizes year 1 blinded data from a 5-year prospective, randomized (1:1, stratified by race and donor type), multicenter, double-blind study comparing treatment failure rates between early cessation of corticosteroid therapy and long-term corticosteroid maintenance therapy in 397 primary renal transplant recipients receiving tacrolimus and mycophenolate mofetil with antibody induction. Sixteen (4.1%) patients died or experienced graft loss during year 1 (9 deaths, 6 graft losses, and 1 death with a graft loss). Fifty-nine (15.3%) patients experienced rejection; 40 (10.4%) of these cases were biopsy-confirmed. Values for 10-year predictive risk of coronary heart disease (CHD) estimated from the Framingham Heart Study scores showed a shift from baseline toward a more favorable risk profile. Renal transplant recipients treated with a tacrolimus-based immunosuppressive regimen and either early cessation or maintenance of corticosteroid therapy experienced excellent patient and graft survival, low acute rejection rates, low rate of posttransplantation diabetes mellitus (9.0%), and improved CHD risk profile at 1 year posttransplantation.

Acute Disease↗
PubMed1995

Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes.

OBJECTIVE: To develop a consensus on the use of antenatal corticosteroids for fetal maturation in preterm infants. PARTICIPANTS: A nonfederal, nonadvocate, 16-member consensus panel including representatives from neonatology, obstetrics, family medicine, behavioral medicine, psychology, biostatistics, and the public; 19 experts in neonatology, obstetrics, and pharmacology presented data to the consensus panel and a conference audience of approximately 500. EVIDENCE: An extensive bibliography of references was produced for the consensus panel and the conference audience using a variety of on-line databases including MEDLINE. The consensus panel met several times prior to the conference to review the literature. It also commissioned an updated meta-analysis, a neonatal registry review, and an economic analysis that were presented at the conference. The experts prepared abstracts for distribution at the conference, presented data, and answered questions from the panel and audience. The panel evaluated the strength of the scientific evidence using the grading system developed by the Canadian Task Force on the Periodic Health Examination and adapted by the US Preventive Services Task Force. CONSENSUS: The consensus panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The consensus panel composed a draft statement that was read in its entirety at the conference for comment. The panel released a revised statement at the end of the conference and finalized the revisions a few weeks after the conference. CONCLUSIONS: Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health care costs. The use of antenatal corticosteroids for fetal maturation is a rare example of a technology that yields substantial cost savings in addition to improving health.

Betamethasone↗
PubMed2004

Optimizing the extraction and analysis of DHEA sulfate, corticosteroids and androgens in urine: application to a study of the influence of corticosteroid intake on urinary steroid profiles.

A method of detecting and quantifying dehydroepiandrosterone (DHEA) sulfate, corticosteroids, and androgens has been developed. All of the compounds were first extracted from urine using solid phase extraction (SPE), enzymatically hydrolyzed, and separated into three samples using a second SPE. A DHEA sulfate sample was acetylated and re-extracted using SPE for purification before analysis. Corticosteroid samples were oxidized and re-extracted using liquid/liquid extraction for analysis. Androgen samples were acetylated and re-extracted using SPE prior to analysis. The extraction and analysis methods were investigated and optimized. Analyses were performed with gas chromatography/mass spectrometry (GC/MS) and gas chromatography/flame ionization detection (GC/FID). The entire procedure was then applied to the study of urine profiles of healthy volunteers and patients treated with corticosteroids. The results showed that the quantities of androgens found in patient urines were lower than in those of healthy volunteers. In addition, other metabolites were detected in patient urines.

Adrenal Cortex Hormones↗
PubMed2005

Body weight alterations under early corticosteroid withdrawal and chronic corticosteroid therapy with modern immunosuppression.

UNLABELLED: Weight gain is a well-known complication of corticosteroid maintenance therapy. The purpose of our study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) to those observed under early corticosteroid withdrawal (CSWD) in renal transplant recipients. METHODS: Renal transplant recipients who underwent early CSWD in IRB-approved prospective trials were compared to a historical control group of patients receiving CCST who were matched for age, sex, and race. RESULTS: One hundred sixty-nine patients with early CSWD were compared to 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 12 months (5.52 kg vs 3.05 kg, P < .05) posttransplant. Caucasian CSWD patients demonstrated a greater reduction in weight gain with CSWD than African Americans (mean weight decrease 2.9 vs 1.9 kg/patient, P < .05). Patients who were overweight (body mass index [BMI] 25-30) or obese (BMI > 30) demonstrated a greater reduction in weight gain with CSWD at 1 year (mean reduction in weight gain with CSWD 5.3 kg/patient and 4.4 kg/patient) than did patients of normal weight (BMI < 25; 0.1 kg/patient, P < .01 and <.05 versus BMI < 25). CONCLUSIONS: Early CSWD patients gain significantly less weight than CCST patients following transplantation. Marked variations in the effect of early CSWD on weight gain may be observed due to race and pretransplant BMI. Caucasians and overweight patients demonstrate greater benefits from CSWD than African Americans and patients with normal BMI.

Adrenal Cortex Hormones↗
PubMed1992

A randomized prospective trial comparing a defined formula diet, corticosteroids, and a defined formula diet plus corticosteroids in active Crohn's disease.

Although defined formula diets may be useful for initial episodes of Crohn's disease, the effects of these diets on subsequent attacks of Crohn's disease or in conjunction with corticosteroids are unknown. To evaluate these issues, we studied 27 patients in a randomized prospective trial. Ten patients received only prednisone (group I), nine received only a defined formula diet (Vital HN [high nitrogen]) (group II), and eight received a combination of prednisone and Vital HN (group III). At the time of entry into the study, the groups were similar with respect to age, sex, Crohn's Disease Activity Index, previous and current treatments, anatomic site of disease, and nutritional status. After 1 month of treatment, we noted seven successes (70%) and three failures in group I (prednisone only), three successes (33%) and six failures in group II (Vital HN only), and six successes (75%) and two failures in group III (combination therapy). Four patients randomized to receive only Vital HN were unable or unwilling to tolerate the defined formula diet. Of the five patients who were able to take the defined formula diet for 1 month, however, three (60%) were successfully treated. The patients who received prednisone (groups I and III) responded better than did the patients who received only the defined formula diet. These results may be attributable to the use of a nonelemental diet or the treatment of patients who were not experiencing an initial attack of Crohn's disease or who had previously received corticosteroids. The expensive and often poorly tolerated defined formula diets should not be considered as a substitute for standard therapy with corticosteroids in Crohn's disease.

Adult↗
PubMed2004

Oral corticosteroid-sparing effects of inhaled corticosteroids in the treatment of persistent and acute asthma.

OBJECTIVE: To review the efficacy and safety of inhaled corticosteroids (ICSs) when used to reduce daily oral corticosteroid (OCS) requirements in patients with severe persistent asthma and periodic requirements in patients with acute asthma exacerbations. DATA SOURCES: Clinical studies of the OCS-sparing effects of ICSs were located by searching MEDLINE databases from 1966 onward using the terms oral, steroid, and asthma in combination with the generic names for each marketed ICS. STUDY SELECTION: Studies reporting on the use of ICSs to reduce OCS requirements in patients with persistent and acute asthma are included. RESULTS: Clinical study results consistently show that ICSs significantly improve asthma control and reduce OCS requirements among adults, children, and infants with persistent asthma. A dose reduction or complete discontinuation of use of OCSs is possible in most patients without loss of asthma control. ICSs also can control asthma during acute asthma exacerbations and reduce the need for short courses of OCSs. With many ICSs, the reductions in OCS use are accompanied by recovery of hypothalamic-pituitary-adrenal axis function, indicating that the safety of asthma therapy is improved when OCS requirements are decreased with ICSs. Of the available ICSs that may reduce OCS needs, budesonide appears to be the most intensively studied. CONCLUSIONS: ICSs can reduce OCS requirements in adults and children with persistent asthma and during acute asthma exacerbations. The reduced systemic corticosteroid activity associated with ICS treatment improves the overall safety of asthma therapy.

Administration, Inhalation↗
PubMed2000

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Adolescent↗
PubMed2006

Neurodevelopmental and respiratory follow-up results at 7 years for children from the United Kingdom and Ireland enrolled in a randomized trial of early and late postnatal corticosteroid treatment, systemic and inhaled (the Open Study of Early Corticosteroid Treatment).

OBJECTIVES: The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (<3 days) or delayed selective (>15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment. METHODS: One hundred twenty-seven (84%) of 152 survivors from the United Kingdom and Ireland who were recruited to the Open Study of Early Corticosteroid Treatment, a randomized trial of inhaled and systemic corticosteroid therapy to prevent chronic lung disease, were traced and assessed at a median age of 7 years. Outcome measures were level of disability, presence of cerebral palsy, cognitive ability, behavioral difficulties and competencies, growth, and respiratory symptoms. Results were adjusted for potential confounding variables (gestational age, birth weight, gender, prenatal steroid therapy, method of delivery, Apgar score at 5 minutes, and Clinical Risk Index for Babies score). RESULTS: There were no significant differences among the treatment groups in cognitive ability, behavioral competencies or difficulties, overall disability rates, cerebral palsy, combined outcomes of death or cerebral palsy and death or moderate/severe disability, growth, respiratory morbidity, or diastolic blood pressure. Those assigned to dexamethasone were more likely to have high systolic blood pressure and to have a diagnosis of asthma than were those assigned to budesonide. CONCLUSIONS: Although postnatal steroid therapy has been associated with poor long-term outcomes, this study failed to show significant differences in cognitive function between dexamethasone- and budesonide-allocated groups. There may be increased systolic blood pressure and a greater likelihood of developing asthma in childhood after postnatal dexamethasone treatment.

Administration, Inhalation↗
PubMed1998

Increased corticosteroid binding capacity of plasma albumin but not of corticosteroid-binding globulin caused by ACTH-induced changes in free fatty acid concentrations in snowshoe hares and rabbits.

Free fatty acids (FFAs) are rapidly mobilized by ACTH and have been shown to be potent endogenous modulators of steroid-protein interactions. We increased FFA in lagomorphs by ACTH and then separated the transient increase in glucocorticoid binding capacity of plasma into that accounted for by changes in binding to albumin and to corticosteroid-binding globulin (CBG). Sequential injections of dexamethasone and ACTH into both snowshoe hares and laboratory rabbits resulted in the rapid mobilization of FFA only after the ACTH injection. The maximum corticosteroid binding capacity increase paralleled that of the FFA increase in both species. In rabbits, CBG levels remained constant over the duration of the experiment. Corticosterone binding by rabbit albumin increased in a dose-dependent fashion in response to increases in FFA (oleic and linoleic acid) concentrations. Finally, by stimulating FFA release in snowshoe hares with ACTH and separating the increase in corticosteroid binding capacity through selective denaturing of CBG by heat, we determined that the increase in plasma binding capacity was a response to changes in binding by albumin, not CBG. Thus FFA released in response to stressors in lagomorphs may effect short-term increases in steroid binding.

Adrenal Cortex Hormones↗
PubMed1975

[The inhibitory effects of corticosteroid on the proliferation of tumor cells derived from human astrocytoma-gliobastoma--with special reference to combined vasopressin--corticosteroid therapy (author's transl)].

In view of the fact that clinical reports have been recently made that combined varopressin-corticosteroid therapy is remarkably effective against recurrent malignant astrocytoma, it is considered necessary to review the antitimor action of steroids against glioma. The effects of hydrocortisone sodium succinate were studied on cultured cells derived from 17 glioma cases composed of 8 cases of glioblastoma (grade III, IV) and 9 cases of benign astrocytoma (grade I, II). Actively growing monolayer culture of tumor cells was exposed to the test agent of serially diluted concentration from 10(-4) to 10(-7) g/ml. The effectiveness was estimated by calculating the proliferation rate of cells for 7 days. The response curve of the test agent exhibited a relatively good correlation to dose as well as a good potency in suppressing cellular proliferation. This was more marked in cells from malignant glioma than those from benign glioma. The results also indicate that the inhibitory effects of corticosteroid are closely correlated to the growth rate of the tumor itself. Thus, the therapeutic effects of long-term administration of corticosteroid can be expected not only by the resultant decrease in cerebral edema and in the suppressed production rate of cerebrospinal fluid but also from the standpoint of its anti-timor action. It should be possible to effectively include steroid therapy in the program of surgical procedure, radiation therapy and chemotherapy for glioma patients in whom recurrence is generally almost inevitable.

Adolescent↗
PubMed1977

20beta-Hydroxysteroid oxidoreductase. Kinetics and binding of corticosteroids and corticosteroid-21-aldehydes.

Corticosteroid-21-aldehydes were reduced only at C-20 by 20 beta-hydroxysteroid dehydrogenase (EC 1.1.1.53) of Streptomyces hydrogenans, and the reduction occurred by transfer of hydrogen from the B-side of NADH. A kinetic investigation of cortisol, cortisone, cortexolone, and the 21-aldehydes of each indicated: (a) the magnitude of the Michaelis constant for any substrate was independent of the second substrate concentration; (b) the 21-aldehydes had larger Michaelis constants (5- to 8-fold) and larger maximum velocities (16- to 40-fold) than the steroids from which they were synthesized; (c) the Michaelis constant for NADH, 29 muM, was independent of the steroid substrate. With cortisol and cortisol-21-aldehyde, product inhibition patterns showed only slope effects with steroid product and NAD+, suggesting a "random" mechanism. Inhibition studies with the "poor" substrate cortisol indicated that cortisol and cortisol-21-aldehyde were reduced at the same site. The inhibition constant (180 muM) agreed with the Michaelis constant of cortisol (140 muM). The steroid product, 20beta-hydroxyprogesterone, gives noncompetitive inhibition patterns with respect to NADH and cortisol-21-aldehyde, indicating a separate binding site exists on the enzyme for this inhibitor. The intrinsic protein fluorescence of 20beta-hydroxysteroid dehydrogenase was quenched by NADH (56%) with a dissociation constant of 16 muM. NAD" quenched the protein fluorescence somewhat less (31%) with a dissociation constant of 104 muM. The fluorescence of 2-p-toluidine-6-naphthalene sulfonate is enhanced in the presence of enzyme, and there is a blue shift in the emission wavelength maximum. The enzyme-enhanced 2-p-toluidine-6-naphthalene sulfonate fluorescence is quenched by NAD+ (32%) with a dissociation constant of 128 muM. Corticosteroids and their corresponding 21-aldehydes completely quench the enhanced 2-p-toluidine-6-naphthalene sulfonate fluorescence and this feature can be used to determine enzyme-steroid dissociation constants. Corticosteroid-21-aldehydes and NAD+ dissociation constants determined in this manner agree with values obtained in kinetic measurements. The dissociation constants determined for cortisol, cortisone, cortexolone, progesterone, and 20beta-hydroxyprogesterone were at least 1 order of magnitude greater than the corresponding kinetic constants, and these findings suggest the presence of a kinetically insignificant binding site.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Should corticosteroids be used in the treatment of acute, severe asthma? I. A case for the use of corticosteroids in acute, severe asthma.

Corticosteroids have been used for over 3 decades in the treatment of asthma. There are theoretic reasons and long-standing clinical support for their use, but little in the way of good objective data on their efficacy. I have reviewed this information and concluded that notwithstanding rare side effects, corticosteroids should be used in acute asthma, and objective data exist to support this premise.

Adrenal Cortex Hormones↗
PubMed1992

Comparison of serum amyloid A and C-reactive protein as indicators of lung inflammation in corticosteroid treated and non-corticosteroid treated cystic fibrosis patients.

Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830 serum samples from 155 cystic fibrosis (CF) patients. Correlation coefficients were calculated for all samples (r = 0.73), for samples from non-corticosteroid treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid treated (CFS) patients (n = 132, r = 0.35). SAA was the more sensitive indicator of pulmonary inflammation when SAA and CRP were compared to pulmonary function tests of 49 hospitalized patients at admission and discharge. CRP levels were significantly (p less than .05) lower at admission in CFS patients than in CFNS patients, whereas SAA levels were not significantly different between the two groups. All nine CFS patients hospitalized had elevated SAA levels (average 22 times above normal limits) at admission, while only six had elevated CRP levels (average 3.7 times above normal limits) at admission. In the 40 CFNS patients both SAA and CRP levels were significantly elevated at admission. In each case SAA and CRP levels declined as pulmonary functions improved with effective antimicrobial therapy. In three instances SAA levels increased during hospitalization while CRP levels did not. In each case, rising SAA levels indicated clinical deterioration associated with evolving resistance of P. aeruginosa which required a change in antibiotic therapy.

Adolescent↗
PubMed2005

Comparative improvement of asthma symptoms and expiratory flows after corticosteroid treatment: a method to assess the effect of corticosteroids on large vs. small airways?

The magnitude of improvement of respiratory symptoms (RS) and expiratory flows (EF) following corticosteroid treatment may vary from one asthmatic patient to another. The distribution of ratio of improvement of the above parameters was assessed in 937 patients with asthma of variable severity who took part in three clinical trials comparing the effects of chlorofluorocarbon-propelled beclomethasone dipropionate (CFC-BDP) with similar (n:316) or half-doses (n:581) of extrafine hydrofluoroalkane-propelled (HFA-BDP) on asthma control. We calculated the ratio of improvement of shortness of breath, wheezing, sleep disturbance, cough, and chest tightness over the following physiological parameters: forced expiratory volume in 1s (FEV1), FEF(25/75%), morning peak expiratory flow, and FVC, from the baseline value to the last set of measures in the study, while on the study medication. We hypothesized that the ratio of RS/EF would have a normal distribution and would be higher with extrafine HFA-BDP compared with CFC-BDP, which has a larger particle size, when FEV1 is used, as it mostly assesses large airways. Ratios of improvement were normally distributed for both drugs and no significant shift in its distribution curve was found for HFA-BDP. The ratio of changes in FEF(25/75%)/FEV1 was similar in the two groups. In conclusion, the ratio of improvement of RS/EF is normally distributed over a narrow range, showing a generally good correlation between improvements in EF and symptoms in asthma; it was, however, similar for the two BDP molecules tested. This may suggest that this ratio is not useful for evaluating the effect of corticosteroids on small airways, or that extrafine HFA-BDP acts at the level of large- to moderate-caliber airways to produce most of its beneficial effect.

Administration, Inhalation↗