Adrenal Suppression

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M I Mulford - One of the best experts on this subject based on the ideXlab platform.

Brian J. Lipworth - One of the best experts on this subject based on the ideXlab platform.

  • Adrenal Suppression with dry powder formulations of fluticasone propionate and mometasone furoate
    American Journal of Respiratory and Critical Care Medicine, 2004
    Co-Authors: Thomas C Fardon, Lesley C. Mcfarlane, K Haggart, Brian J. Lipworth
    Abstract:

    Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of Adrenal Suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 μg/day) or MF Twisthaler (400, 800, and 1,600 μg/day). For the 21 per protocol completed patients, there was significant Suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs—as geometric mean fold Suppression (95% confidence interval) from baseline: FP 2,000 μg, 1.85 (1.21–2.82, p = 0.002); FP 1,000 μg, 1.45 (1.07–1.96, p = 0.02); MF 1,600 μg, 1.92 (1.26–2.93, p = 0.001); and MF 800 μg, 1.39 (1.04–1.88, p = 0.02). For secondary outcomes of 8:...

  • Adrenal Suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers.
    European Journal of Clinical Pharmacology, 1997
    Co-Authors: Andrew M. Wilson, D. J. Clark, Lesley C. Mcfarlane, Brian J. Lipworth
    Abstract:

    Study objective: This study was conducted to compare the Adrenal Suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers, both given via their respective pressurised metered dose inhaler (pMDI) devices at high doses within the manufacturers recommended dose range.

  • comparative Adrenal Suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients
    Thorax, 1996
    Co-Authors: D. J. Clark, Alison Grove, Robert I Cargill, Brian J. Lipworth
    Abstract:

    BACKGROUND: A study was performed to compare the Adrenal Suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage Suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH Suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater Adrenal Suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Dennis Carson - One of the best experts on this subject based on the ideXlab platform.

  • monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict Adrenal Suppression
    Archives of Disease in Childhood, 2004
    Co-Authors: Kathryn Anne Dunlop, J Mcnaboe, Dennis Carson, H J Steen, Vincent Mcgovern, Michael D Shields
    Abstract:

    Aims: To determine whether routine outpatient monitoring of growth predicts Adrenal Suppression in prepubertal children treated with high dose inhaled glucocorticoid. Methods: Observational study of 35 prepubertal children (aged 4–10 years) treated with at least 1000 μg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding Adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal Suppression was defined as a peak cortisol ⩽500 nmol/l. Results: The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of Adrenal insufficiency 6 and 12 months prior to Adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of −0.5 for Adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (ρ = 0.23, p = 0.19 at 6 months; ρ = 0.33, p = 0.06 at 12 months). Conclusions: Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious Adrenal Suppression. Both growth and Adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring Adrenal function.

  • growth and Adrenal Suppression in asthmatic children treated with high dose fluticasone propionate
    The Lancet, 1996
    Co-Authors: G Todd, K Dunlop, J Mcnaboe, M F Ryan, Dennis Carson
    Abstract:

    Summary Background Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200μg/day, but not at the higher doses that are often used. Methods Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/ creatinine ratio in one. Findings Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have Adrenal Suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500μg/day. Interpretation When high doses of fluticasone propionate are used, growth may be retarded and Adrenal Suppression may occur.

E O Gilbertson - One of the best experts on this subject based on the ideXlab platform.

Alexandra Ahmet - One of the best experts on this subject based on the ideXlab platform.

  • Adrenal Suppression from glucocorticoids: preventing an iatrogenic cause of morbidity and mortality in children
    BMJ paediatrics open, 2019
    Co-Authors: Alexandra Ahmet, Ellen B Goldbloom, Arati Mokashi, Céline Huot, Roman Jurencak, Preetha Krishnamoorthy, Anne Rowan-legg, Larry Pancer, Thomas Kovesi
    Abstract:

    Adrenal Suppression (AS) is an important side effect of glucocorticoids (GCs) including inhaled corticosteroids (ICS). AS can often be asymptomatic or associated with non-specific symptoms until a physiological stress such as an illness precipitates an Adrenal crisis. Morbidity and death associated with Adrenal crisis is preventable but continues to be reported in children. There is a lack of consensus about the management of children at risk of AS. However, healthcare professionals need to develop an awareness and approach to keep these children safe. In this article, current knowledge of the risk factors, diagnosis and management of AS are reviewed while drawing attention to knowledge gaps and areas of controversy. Possible strategies to reduce the morbidity associated with this iatrogenic condition are provided for healthcare professionals.

  • symptomatic Adrenal Suppression among children in canada
    Archives of Disease in Childhood, 2017
    Co-Authors: Ellen B Goldbloom, Arati Mokashi, Elizabeth A Cummings, Sharon Abish, Susanne M Benseler, Hien Q Huynh, Wade Watson, Alexandra Ahmet
    Abstract:

    Background Adrenal Suppression (AS) is an under-recognised side effect of glucocorticoid (GC) use. AS may go undetected until a physiological stress precipitates an Adrenal crisis. The incidence of AS has not been established. We sought to estimate the minimum national incidence and presenting features of paediatric symptomatic AS. Methods Through the established methodology of the Canadian Paediatric Surveillance Program, over 2500 paediatricians were surveyed monthly for 2 years (April 2010–March 2012) to report new cases of symptomatic AS. Results Forty-six cases of symptomatic AS were confirmed. The estimated annual incidence is 0.35/100 000 children aged 0–18 years (95% CI 0.26 to 0.47). The most common presentations were growth failure (35%), non-specific symptoms (28%) or both (13%). Adrenal crisis occurred in six cases (13%). Thirty-seven children (80%) had received inhaled corticosteroid (ICS) alone or in combination with other GC forms. Many children received high but commonly prescribed doses of ICS. Conclusions AS is responsible for significant morbidity in children, including susceptibility to Adrenal crisis. The minimal estimated incidence reported is for the entire paediatric population and would be much higher in the at-risk group (ie, children treated with GCs). Close monitoring of growth and possible symptoms of AS, which may be non-specific, are important in children on all forms of GC therapy including ICS. To reduce the risk of AS, physicians must be aware of the risk of AS, revisit GC doses frequently and use the lowest effective dose.

  • Adrenal Suppression in Pediatric Patients during Treatment for Acute Lymphoblastic Leukemia
    Blood, 2015
    Co-Authors: Mary-pat Schlosser, Alexandra Ahmet, Daniel Burd, Sarah Lawrence, Mylene Bassal
    Abstract:

    Background: Hypothalamic-pituitary-Adrenal (HPA) axis Suppression is a form of Adrenal insufficiency that can be found following the use of corticosteroids. Individuals with Adrenal insufficiency may have non-specific symptoms or even no regular symptoms, however if presented with a physiologic stress such as infection, injury, or surgery, they are at risk of Adrenal crisis. Adrenal crisis typically manifests with hypoglycemia, hypotension and critical illness; this condition is associated with significant morbidity and even mortality. Children being treated for leukemia are at increased risk of infection and may require surgical procedures, thus putting them at risk of Adrenal crisis in the context of Adrenal Suppression. It is known that Adrenal Suppression exists in the short term after the induction phase of treatment in patients with acute lymphoblastic leukemia (ALL), but the prevalence and duration of Suppression is still not fully understood. In addition, Adrenal Suppression has not been specifically evaluated during the maintenance phase of therapy. During maintenance there may be ongoing Adrenal Suppression from steroid use in induction, or new Suppression from steroid use for maintenance therapy itself. There does not yet exist an accepted protocol to monitor for Adrenal insufficiency in ALL. Knowing the prevalence and duration of Adrenal Suppression in maintenance will enable care teams to better recognize and manage the condition, potentially preventing significant morbidity and mortality. Methods: All cases of ALL treated at the Children9s Hospital of Eastern Ontario from 2000 to 2014 were retrospectively reviewed for Adrenal Suppression. Patient characteristics, clinical features, laboratory data, treatment protocol utilized, adverse events and outcomes were examined. Results: 176 patients were diagnosed with new ALL at The Children9s Hospital of Eastern Ontario between 2000 and 2014. Prompted by clinical suspicion, 24 had testing done to investigate for Adrenal Suppression during this time period. 9 of those patients had cortisol levels indicative of Adrenal Suppression and required further management for the same. Adrenal Suppression was identified in early phases of treatment for ALL. Adrenal Suppression was also identified in patients during the maintenance phase of treatment. Many more patients had symptoms that could be attributed to Adrenal Suppression, but never had cortisol levels tested. Conclusion: Adrenal Suppression is found in children being treated for ALL, including during the maintenance phase of therapy. Adrenal Suppression may have been present in greater numbers of children, but no routine testing protocol exists to identify these patients. Identifying and reviewing cases of Adrenal Suppression in children during treatment for ALL, including the maintenance phase, gives a better understanding of the risk of HPA axis Suppression in this population. This study also provides background data for the development of a prospective study to further look at Adrenal Suppression in the maintenance phase of ALL. These studies will guide development of a testing protocol to better identify and manage Adrenal Suppression, thereby reducing its morbidity and mortality, in children being treated for ALL. Disclosures No relevant conflicts of interest to declare.

  • reversal of Adrenal Suppression with ciclesonide
    Journal of Asthma, 2010
    Co-Authors: Mariel Kupfert Heller, Jessica Laks, Thomas Kovesi, Alexandra Ahmet
    Abstract:

    Background. Adrenal Suppression secondary to high-dose inhaled corticosteroid use has been reported in children. Methods. The authors report the use of ciclesonide to reverse Adrenal Suppression secondary to inhaled fluticasone use in four pediatric patients. Results. In these four children, hypothalamic-pituitary-Adrenal axis function normalized after the patients were changed to ciclesonide, while good asthma control was maintained. Conclusions. Ciclesonide should be considered for the reversal of Adrenal Suppression secondary to the use of fluticasone, and perhaps other older inhaled corticosteroids as well.

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