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      Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings

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          Abstract

          Adrenal insufficiency (AI) remains a significant cause of morbidity and mortality in children with 1 in 200 episodes of adrenal crisis resulting in death. The goal of this working group of the Pediatric Endocrine Society Drug and Therapeutics Committee was to raise awareness on the importance of early recognition of AI, to advocate for the availability of hydrocortisone sodium succinate (HSS) on emergency medical service (EMS) ambulances or allow EMS personnel to administer patient’s HSS home supply to avoid delay in administration of life-saving stress dosing, and to provide guidance on the emergency management of children in adrenal crisis. Currently, hydrocortisone, or an equivalent synthetic glucocorticoid, is not available on most ambulances for emergency stress dose administration by EMS personnel to a child in adrenal crisis. At the same time, many States have regulations preventing the use of patient’s home HSS supply to be used to treat acute adrenal crisis. In children with known AI, parents and care providers must be made familiar with the administration of maintenance and stress dose glucocorticoid therapy to prevent adrenal crises. Patients with known AI and their families should be provided an Adrenal Insufficiency Action Plan, including stress hydrocortisone dose (both oral and intramuscular/intravenous) to be provided immediately to EMS providers and triage personnel in urgent care and emergency departments. Advocacy efforts to increase the availability of stress dose HSS during EMS transport care and add HSS to weight-based dosing tapes are highly encouraged.

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          Most cited references52

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          Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

          B Lipworth (1999)
          To appraise the data on systemic adverse effects of inhaled corticosteroids. A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.
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            Extensive expertise in endocrinology. Adrenal crisis.

            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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              Adrenal insufficiency: still a cause of morbidity and death in childhood.

              Adrenal insufficiency is relatively rare in childhood and adolescence. Signs and symptoms may be nonspecific; therefore, the diagnosis may not be suspected early in the course. If unrecognized, adrenal insufficiency may present with life-threatening cardiovascular collapse. Adrenal crisis continues to occur in children with known primary or secondary adrenal insufficiency during intercurrent illness because of failure to increase glucocorticoid dosage. In this article, current knowledge of the incidence, diagnosis, and treatment of adrenal insufficiency in children and factors precipitating adrenal crisis are summarized. Suggestions for prevention of adrenal crisis in patients at risk are provided for health care professionals and families.
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                Author and article information

                Journal
                J Investig Med
                J. Investig. Med
                jim
                jim
                Journal of Investigative Medicine
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1081-5589
                1708-8267
                January 2020
                28 February 2019
                : 68
                : 1
                : 16-25
                Affiliations
                [1 ] departmentDepartment of Pediatrics , University of Minnesota Masonic Children’s Hospital , Minneapolis, Minnesota, USA
                [2 ] departmentDepartment of Pediatrics , Nationwide Children’s Hospital , Columbus, Ohio, USA
                [3 ] departmentDepartment of Pediatrics , Children’s Hospital of Los Angeles , Los Angeles, California, USA
                [4 ] departmentDepartment of Pediatrics , MedStar Georgetown University Hospital , Washington, DC, USA
                [5 ] departmentDepartment of Pediatrics , Le Bonheur Children’s Hospital , Memphis, Tennessee, USA
                [6 ] departmentDepartment of Pediatrics , Massachusetts General Hospital , Boston, Massachusetts, USA
                [7 ] departmentDepartment of Pediatrics , UH Rainbow Babies and Children’s Hospital , Cleveland, Ohio, USA
                [8 ] departmentDepartment of Pediatrics and Child Health , University of Manitoba , Winnipeg, Manitoba, Canada
                Author notes
                [Correspondence to ] Dr Bradley S Miller, Department of Pediatrics, University of Minnesota Masonic Children’s Hospital, 2450 Riverside Ave, Minneapolis, MN 55454, USA; mille685@ 123456umn.edu
                Author information
                http://orcid.org/0000-0003-3663-5473
                Article
                jim-2019-000999
                10.1136/jim-2019-000999
                6996103
                30819831
                6ee25c7b-cb0d-472c-88eb-25e5863ff744
                © American Federation for Medical Research 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 7 February 2019
                Categories
                Review
                1506
                1507
                Custom metadata
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                editors-choice

                adrenal insufficiency,pituitary-adrenal system,glucocorticoids,endocrinology

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