The Experts below are selected from a list of 2007 Experts worldwide ranked by ideXlab platform
G R G Todd - One of the best experts on this subject based on the ideXlab platform.
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Adrenal Crisis due to inhaled steroids is underestimated
Archives of Disease in Childhood, 2003Co-Authors: G R G ToddAbstract:In response to comments by Pearce and Mabin on Professor Russell’s editorial1 on our paper.2 They doubt that our survey underestimated the true scale of the problem. I can inform themthat this is not the case. Since our survey was completed we have been notified of a further seven cases (five children, two adults). All but one of the children had been taking fluticasone in similar dosages to those reported in our survey. Three of these were critically ill in intensive care and an 8-year-old girl died due to Adrenal Crisis. The remaining child was only 20 months old and had been given budesonide in extremely high doses of 2000–8000 mcg/day.3 Both adults had been taking fluticasone (1000 mcg/day, 2250 mcg/day). Case reporting clearly plays a much greater role than clinical studies in post license surveillance of new drugs. In an …
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survey of Adrenal Crisis associated with inhaled corticosteroids in the united kingdom
Archives of Disease in Childhood, 2002Co-Authors: G R G Todd, Carlo L Acerini, R Rossrussell, S Zahra, Justin T Warner, D MccanceAbstract:Background: Until recently, only two cases of acute Adrenal Crisis associated with inhaled corticosteroids (ICS) had been reported worldwide. We identified four additional cases and sought to survey the frequency of this side effect in the United Kingdom. Methods: Questionnaires were sent to all consultant paediatricians and adult endocrinologists registered in a UK medical directory, asking whether they had encountered asthmatic patients with acute Adrenal Crisis associated with ICS. Those responding positively completed a more detailed questionnaire. Diagnosis was confirmed by symptoms/signs and abnormal hypothalamic-pituitary-Adrenal axis function test results. Results: From an initial 2912 questionnaires, 33 patients met the diagnostic criteria (28 children, five adults). Twenty-three children had acute hypoglycaemia (13 with decreased levels of consciousness or coma; nine with coma and convulsions; one with coma, convulsions and death); five had insidious onset of symptoms. Four adults had insidious onset of symptoms; one had hypoglycaemia and convulsions. Of the 33 patients treated with 500–2000 μg/day ICS, 30 (91%) had received fluticasone, one (3%) fluticasone and budesonide, and two (6%) beclomethasone. Conclusions: The frequency of acute Adrenal Crisis was greater than expected as the majority of these patients were treated with ICS doses supported by British Guidelines on Asthma Management. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases. We therefore advise that the licensed dosage of fluticasone for children, 400 μg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma. We would also emphasise that until Adrenal function has been assessed patients receiving high dose ICS should not have this therapy abruptly terminated as this could precipitate Adrenal Crisis.
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acute Adrenal Crisis in asthmatics treated with high dose fluticasone propionate
European Respiratory Journal, 2002Co-Authors: G R G Todd, Carlo L Acerini, R Rossrussell, Justin T Warner, J J Buck, Nuala Murphy, D MccanceAbstract:Four cases of asthma (one adult, three children) developing acute Adrenal Crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7–9 yrs, had been prescribed inhaled fluticasone, dosage 500–2,000 µg·day −1 and duration 5 months–5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3–1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000–2,000 µg·day −1 for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute Adrenal Crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-Adrenal axis suppression were excluded.
B Allolio - One of the best experts on this subject based on the ideXlab platform.
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timelines in the management of Adrenal Crisis targets limits and reality
Clinical Endocrinology, 2015Co-Authors: Stefanie Hahner, Christina Spinnler, Felix Beuschlein, Marcus Quinkler, Nina Hemmelmann, B AllolioAbstract:SummaryObjective To evaluate current management timelines in Adrenal Crisis (AC) and to establish time targets and time limits for emergency treatment. Design/patients Patients from a prospective study who had reported an AC (n = 46) were contacted and asked about management of their AC. A survey among 24 European endocrinologists collected expert recommendations concerning time targets and time limits for contact–arrival time of emergency health professionals and presentation of emergency card–glucocorticoid (GC) injection time. Results Median time targets and time limits regarded by experts as adequate for contact–arrival time were 45 and 90 min, respectively, and for card–injection time 15 and 30 min, respectively. Thirty-seven of 46 patients could be interviewed. All patients were equipped with an emergency card but only 23 (62%) with an emergency kit. Seven patients (19%) were trained in GC self-injection. The median time interval between contacting a health professional and arrival was 20 min (range 2–2880 min); ≤45 min: n = 32 (86%), <90 min: n = 34 (92%). The median time interval between arrival and administration of GC was 30 min (range 2–2400 min); ≤15 min: n = 17 (46%), ≤30 min: n = 20 (54%). Conclusion While the time between contacting health professionals and their arrival was within the limits set by experts, initiation of GC administration was delayed in 46% of patients. Thus, improved management of AC needs to focus on shortening the presentation of card–injection time. Given the current reality in the management of AC, promotion of self-injection of GC (s.c. or i.m.) is warranted.
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extensive expertise in endocrinology Adrenal Crisis
European Journal of Endocrinology, 2015Co-Authors: B AllolioAbstract:Adrenal Crisis is a life-threatening emergency contributing to the excess mortality of patients with Adrenal insufficiency. Studies in patients on chronic replacement therapy for Adrenal insufficiency have revealed an incidence of 5-10 Adrenal crises/100 patient years and suggested a mortality rate from Adrenal Crisis of 0.5/100 patient years. Patients with Adrenal Crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of Adrenal Crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of Adrenal Crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of Adrenal Crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending Crisis are expected to significantly reduce morbidity and mortality from Adrenal Crisis.
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high incidence of Adrenal Crisis in educated patients with chronic Adrenal insufficiency a prospective study
The Journal of Clinical Endocrinology and Metabolism, 2015Co-Authors: Stefanie Hahner, Christina Spinnler, Martin Fassnacht, Stephanie Burgerstritt, Katharina Lang, Danijela Milovanovic, Felix Beuschlein, Holger S Willenberg, Marcus Quinkler, B AllolioAbstract:Objective: Adrenal Crisis (AC) is a life-threatening complication of Adrenal insufficiency (AI), which according to retrospective data represents a significant clinical complication. Here we aimed to prospectively assess incidence of AC and mortality associated with AC in patients with chronic AI. Methods: A total of 423 patients with AI (primary AI, n = 221; secondary AI, n = 202) were prospectively followed up for 2 years. Baseline assessment included a general questionnaire and detailed written instructions on glucocorticoid dose adaptation during stress. Patients received follow-up questionnaires every 6 months and were contacted by phone in case of reported Adrenal Crisis. Results: A total of 423 data sets were available for baseline analysis, and 364 patients (86%) completed the whole study. Sixy-four AC in 767.5 patient-years were documented (8.3 crises per 100 patient-years). Precipitating causes were mainly gastrointestinal infection, fever, and emotional stress (20%, respectively) but also other...
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epidemiology of Adrenal Crisis in chronic Adrenal insufficiency the need for new prevention strategies
European Journal of Endocrinology, 2010Co-Authors: Stefanie Hahner, Martin Fassnacht, Danijela Milovanovic, Marcus Quinkler, M Ventz, Melanie Loeffler, Benjamin Bleicken, Christiane Drechsler, B AllolioAbstract:Objective: Adrenal Crisis (AC) is a life-threatening complication of Adrenal insufficiency (AI). Here, we evaluated frequency, causes and risk factors of AC in patients with chronic AI. Methods: In a cross-sectional study, 883 patients with AI were contacted by mail. Five-hundred and twenty-six patients agreed to participate and received a disease-specific questionnaire. Results: Four-hundred and forty-four datasets were available for analysis (primary AI (PAI), nZ254; secondary AI (SAI), nZ190). Forty-two percent (PAI 47% and SAI 35%) reported at least one Crisis. Three hundred and eighty-four AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat and pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6% and SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5 vs 28.4%, PZ0.003). Crisis incidence was not influenced by educational status, body mass index, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or GH deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of Crisis (odds ratio (OR)Z2.02, 95% confidence interval (CI) 1.05‐3.89, PZ0.036). In SAI, female sex (ORZ2.18, 95% CI 1.06‐4.5, PZ0.035) and diabetes insipidus (ORZ2.71, 95% CI 1.22‐5.99, PZ0.014) were associated with higher Crisis incidence. Conclusion: AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of Crisis prevention in patients with AI.
D Mccance - One of the best experts on this subject based on the ideXlab platform.
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survey of Adrenal Crisis associated with inhaled corticosteroids in the united kingdom
Archives of Disease in Childhood, 2002Co-Authors: G R G Todd, Carlo L Acerini, R Rossrussell, S Zahra, Justin T Warner, D MccanceAbstract:Background: Until recently, only two cases of acute Adrenal Crisis associated with inhaled corticosteroids (ICS) had been reported worldwide. We identified four additional cases and sought to survey the frequency of this side effect in the United Kingdom. Methods: Questionnaires were sent to all consultant paediatricians and adult endocrinologists registered in a UK medical directory, asking whether they had encountered asthmatic patients with acute Adrenal Crisis associated with ICS. Those responding positively completed a more detailed questionnaire. Diagnosis was confirmed by symptoms/signs and abnormal hypothalamic-pituitary-Adrenal axis function test results. Results: From an initial 2912 questionnaires, 33 patients met the diagnostic criteria (28 children, five adults). Twenty-three children had acute hypoglycaemia (13 with decreased levels of consciousness or coma; nine with coma and convulsions; one with coma, convulsions and death); five had insidious onset of symptoms. Four adults had insidious onset of symptoms; one had hypoglycaemia and convulsions. Of the 33 patients treated with 500–2000 μg/day ICS, 30 (91%) had received fluticasone, one (3%) fluticasone and budesonide, and two (6%) beclomethasone. Conclusions: The frequency of acute Adrenal Crisis was greater than expected as the majority of these patients were treated with ICS doses supported by British Guidelines on Asthma Management. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases. We therefore advise that the licensed dosage of fluticasone for children, 400 μg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma. We would also emphasise that until Adrenal function has been assessed patients receiving high dose ICS should not have this therapy abruptly terminated as this could precipitate Adrenal Crisis.
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acute Adrenal Crisis in asthmatics treated with high dose fluticasone propionate
European Respiratory Journal, 2002Co-Authors: G R G Todd, Carlo L Acerini, R Rossrussell, Justin T Warner, J J Buck, Nuala Murphy, D MccanceAbstract:Four cases of asthma (one adult, three children) developing acute Adrenal Crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7–9 yrs, had been prescribed inhaled fluticasone, dosage 500–2,000 µg·day −1 and duration 5 months–5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3–1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000–2,000 µg·day −1 for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute Adrenal Crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-Adrenal axis suppression were excluded.
Leonie H A Broersen - One of the best experts on this subject based on the ideXlab platform.
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The incidence of Adrenal Crisis in the postoperative period of HPA axis insufficiency after surgical treatment for Cushing’s syndrome
European Journal of Endocrinology, 2019Co-Authors: Leonie H A Broersen, Femke M. Van Haalen, Tina Kienitz, Olaf M. Dekkers, Christian J Strasburger, Alberto M. Pereira, Nienke R. BiermaszAbstract:Adrenal Crisis, the most feared complication of Adrenal insufficiency, is a potentially life-threatening state of acute glucocorticoid deficiency. After successful surgery for Cushing's syndrome, many patients develop (transient) Adrenal insufficiency. The incidence of Adrenal Crisis in patients treated for hypercortisolism is unknown. Cohort study included consecutive patients with Cushing's syndrome with Adrenal insufficiency after surgery from Leiden and Berlin from 2000 to 2015. We summarized the incidence of Adrenal Crisis, compared patients with and without Adrenal Crisis regarding potential risk factors for its occurrence and assessed the effect of better education in time on incidence of Adrenal Crisis. We included 106 patients, of whom 19 patients had a total of 41 Adrenal crises. There were 9.0 crises per 100 patient-years at risk (95% confidence interval (CI): 6.7-12.0). All crises occurred while on hydrocortisone replacement. The risk ratio for a recurrent Crisis was 2.3 (95% CI: 1.2-4.6). No clear change in incidence of Adrenal Crisis due to better education in time was observed. There was no difference in recurrence rate between patients with, and without any Crisis, but patients with Adrenal Crisis had more often pituitary deficiencies. The incidence of Adrenal crises after treatment for Cushing's syndrome is substantial, and patients who suffered from an Adrenal Crisis have higher risk for recurrent Crisis. Adrenal Crisis tends to present early after remission of Cushing's syndrome, which is probably the period of severest HPA axis suppression, despite in general higher hydrocortisone replacement doses for withdrawal complaints in this period. Additional pituitary hormone deficiencies may be a risk marker for increased risk of Adrenal Crisis. However, further risk factor analysis is needed to identify risks for a first Crisis. Effective education methods to prevent Adrenal crises should be identified and implemented, including stress instructions by trained nursing staff before hospital discharge.
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the incidence of Adrenal Crisis in the postoperative period of hpa axis insufficiency after surgical treatment for cushing s syndrome
European Journal of Endocrinology, 2019Co-Authors: Leonie H A Broersen, Femke M. Van Haalen, Tina Kienitz, Olaf M. Dekkers, Christian J Strasburger, Alberto M. Pereira, Nienke R. BiermaszAbstract:BACKGROUND: Adrenal Crisis, the most feared complication of Adrenal insufficiency, is a potentially life-threatening state of acute glucocorticoid deficiency. After successful surgery for Cushing's syndrome, many patients develop (transient) Adrenal insufficiency. The incidence of Adrenal Crisis in patients treated for hypercortisolism is unknown. METHODS: Cohort study including consecutive patients with Cushing's syndrome with Adrenal insufficiency after surgery from Leiden and Berlin from 2000-2015. We summarized incidence of Adrenal Crisis, compared patients with and without Adrenal Crisis regarding potential risk factors for its occurrence, and assessed the effect of better education in time on incidence of Adrenal Crisis. RESULTS: We included 106 patients, of whom 19 patients had a total of 41 Adrenal crises. There were 9.0 crises per 100 patient-years at risk (95% confidence interval [CI]: 6.7-12.0). All crises occurred while on hydrocortisone replacement. The risk ratio for a recurrent Crisis was 2.3 (95% CI: 1.2-4.6). No clear change in incidence of Adrenal Crisis due to better education in time was observed. There was no difference in recurrence rate between patients with, and without any Crisis, but patients with Adrenal Crisis had more often pituitary deficiencies. CONCLUSIONS: The incidence of Adrenal crises after treatment for Cushing's syndrome is substantial, and patients who suffered from an Adrenal Crisis have higher risk for recurrent Crisis. Adrenal Crisis tends to present early after remission of Cushing's syndrome, which is probably the period of severest HPA-axis suppression, despite in general higher hydrocortisone replacement doses for withdrawal complaints in this period. Additional pituitary hormone deficiencies may be a risk marker for increased risk of Adrenal Crisis. However, further risk factor analysis is needed to identify risks for a first Crisis. Effective education methods to prevent Adrenal crises should be identified and implemented, including stress instructions by trained nursing staff before hospital discharge.
Alessandro Prete - One of the best experts on this subject based on the ideXlab platform.
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prevention of Adrenal Crisis cortisol responses to major stress compared to stress dose hydrocortisone delivery
The Journal of Clinical Endocrinology and Metabolism, 2020Co-Authors: Alessandro Prete, Angela E Taylor, Irina Bancos, David J Smith, Mark Foster, Sibylle KohlerAbstract:CONTEXT: Patients with Adrenal insufficiency require increased hydrocortisone cover during major stress to avoid life-threatening Adrenal Crisis. However, current treatment recommendations are not evidence-based. OBJECTIVE: To identify the most appropriate mode of hydrocortisone delivery in patients with Adrenal insufficiency exposed to major stress. DESIGN AND PARTICIPANTS: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N=83], sepsis [N=100], and combat stress [N=105]). Longitudinal study: 22 patients with preserved Adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary Adrenal insufficiency undergoing administration of 200mg hydrocortisone over 24 hours in four different delivery modes (continuous intravenous infusion; six-hourly oral, intramuscular or intravenous bolus administration). MAIN OUTCOME MEASURE: We measured total serum cortisol and cortisone, free serum cortisol and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modelling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with Adrenal insufficiency exposed to major stress. RESULTS: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modelling identified continuous intravenous infusion of 200mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range. CONCLUSIONS: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of Adrenal Crisis during major stress.
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prevention of Adrenal Crisis cortisol responses to major stress compared to stress dose hydrocortisone delivery in Adrenal insufficiency
medRxiv, 2020Co-Authors: Alessandro Prete, Angela E Taylor, Irina Bancos, David J Smith, Mark Foster, Sibylle Kohler, Violet Fazelsanderson, John Komninos, Donna M Oneil, Dimitra VassiliadiAbstract:Context: Patients with Adrenal insufficiency require increased hydrocortisone cover during major stress to avoid life-threatening Adrenal Crisis. However, current treatment recommendations are not evidence-based. Objective: To identify the most appropriate mode of hydrocortisone delivery in patients with Adrenal insufficiency exposed to major stress. Design and Participants: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N=83], sepsis [N=100], and combat stress [N=105]). Longitudinal study: 22 patients with preserved Adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary Adrenal insufficiency undergoing administration of 200mg hydrocortisone over 24 hours in four different delivery modes (continuous intravenous infusion; six-hourly oral, intramuscular or intravenous bolus administration). Main Outcome Measure: We measured total serum cortisol and cortisone, free serum cortisol and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modelling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with Adrenal insufficiency exposed to major stress. Results: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modelling identified continuous intravenous infusion of 200mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range. Conclusions: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of Adrenal Crisis during major stress.