Efficacy and safety of a hydrocortisone aceponate-containing ear spray solution in dogs with erythemato-ceruminous otitis externa: A randomised, multicentric, single-blinded, controlled trial.

BACKGROUND: Erythemato-ceruminous otitis externa (ECOE) is frequently seen in dogs affected with an allergic skin disease, with recurrent secondary bacteria and yeast overgrowths (detected on cytological examination). OBJECTIVES: The objective of the study was to compare the efficacy and safety of an ear spray containing only hydrocortisone aceponate glucocorticoid diester (HCA) to a control product (CTRL), an approved otic formulation containing prednisolone-miconazole-polymyxin combination, in dogs with ECOE. ANIMALS: In total, 97 and 104 dogs with ECOE were respectively randomly assigned to the tested ear treatment product group (HCA) or the commercially available ear treatment control product group (CTRL). MATERIALS AND METHODS: Dogs were treated for 7-14 days, as needed. At Day (D)0, D7, D14, D28 and D42, Otitis Index Score-3, hearing test, pruritus and pain visual analogue scales, and cytological scores were graded. The overall response to treatment also was assessed. RESULTS: All clinical parameters decreased rapidly and in a similar way without any significant difference at any time between treatment groups. A good-to-excellent response to treatment was seen in >90% of dogs of both groups as early as D14. The treatment was considered safe in all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: A 7- to 14-day ear topical application of HCA alone to dogs with ECOE accompanied with bacterial and/or fungal (yeast) overgrowth was safe and led to no statistical difference in improvement of clinical scores relative to the CTRL combination. Based on these results, it may be necessary to reconsider the routine use of antimicrobial drugs such as antibiotics and antifungals as a first-line treatment for ECOE that is likely to have been caused by an allergic reaction.

Adrenocortical hemorrhage following intravenous tetracosactide in a dog with hypercortisolism.

OBJECTIVE: To summarize findings from a case of adrenocortical hemorrhage following tetracosactide injection during ACTH stimulation testing for monitoring of trilostane therapy in a dog. ANIMAL: A 12-year old neutered male dog with adrenal-dependent hypercortisolism. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: 4 hours after ACTH stimulation testing, the patient developed vomiting, lethargy, and abdominal pain. Abdominal ultrasound was performed before and after an ACTH stimulation test. Following ACTH stimulation testing, there was progressive bilateral adrenal enlargement and free abdominal fluid had developed. This was considered to be caused by adrenocortical inflammation and hemorrhage secondary to the synthetic ACTH analog, tetracosactide, used during stimulation testing. A resting cortisol performed 5 hours after tetracosactide injection was not consistent with iatrogenic hypoadrenocorticism. TREATMENT AND OUTCOME: The patient was managed with analgesia, IV fluids, and corticosteroids and made a full recovery. CLINICAL RELEVANCE: To the authors' knowledge, this was the first reported case of adrenocortical hemorrhage following administration of a synthetic ACTH analog in a dog. This should be considered as a rare potential complication of ACTH stimulation testing.

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Hydrocortisone-associated death and hospital length of stay in patients with sepsis: A retrospective cohort of large-scale clinical care data.

PURPOSE: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset. METHODS: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone. RESULTS: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p < 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p < 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor)epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use. CONCLUSION: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis.

Evaluation of psoriasis patients with long-term topical corticosteroids for their risk of developing adrenal insufficiency, Cushing's syndrome and osteoporosis.

PURPOSE: In this study, we will investigate the possible side effects of psoriasis patients using long-term topical corticosteroids (TCS) such as adrenal insufficiency, Cushing's Syndrome (CS) and osteoporosis and determine how these side effects develop. MATERIAL AND METHODS: Forty-nine patients were included in the study. The patients were divided into two groups based on the potency of the topical steroid they took and the patients' ACTH, cortisol and bone densitometer values were evaluated. RESULTS: There was no significant difference between the two groups regarding the development of surrenal insufficiency, CS and osteoporosis. One patient in group 1 and 4 patients in group 2 were evaluated as iatrogenic CS. ACTH stimulation tests of these patients in group 2 showed consistent results with adrenal insufficiency, while no adrenal insufficiency was detected in the patient in Group 1. Patients who used more than 50g of superpotent topical steroids per week compared to patients who used 50g of superpotent topical steroids per week. It was identified that patients who used more than 50g of superpotent topical steroids had significantly lower cortisol levels, with a negatively significant correlation between cortisol level and the amount of topical steroid use (p < .01).Osteoporosis was detected in 3 patients in group 1 and 8 patients in Group 2. Because of the low number of patients between two groups, statistical analysis could not be performed to determine the risk factors. CONCLUSIONS: Our study is the first study that we know of that investigated these three side effects. We have shown that the development of CS, adrenal insufficiency and osteoporosis in patients who use topical steroids for a long time depends on the weekly TCS dosage and the risk increases when it exceeds the threshold of 50 grams per week. therefore, our recommendation would be to avoid long-term use of superpotent steroids and to choose from the medium-potent group if it is to be used.

Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound in a dog with trilostane-induced hypoadrenocorticism.

A 12-year-old neutered male Chihuahua dog was diagnosed with pituitary-dependent hypercortisolism and treated with trilostane. Eighty-nine days later, the dog showed lethargy accompanied by hyponatraemia and hyperkalaemia. Hypoadrenocorticism due to trilostane was suspected, but the result of the adrenocorticotropic hormone stimulation test was not conclusive. Contrast-enhanced ultrasound showed loss of adrenocortical blood flow in both adrenal glands, indicating adrenocortical hypoperfusion and isolated hypoadrenocorticism. Treatment with fludrocortisone acetate improved the condition and electrolyte abnormalities. Thirteen months later, the dog showed alopecia, and an adrenocorticotropic hormone stimulation test revealed increased cortisol concentration, indicating hypercortisolism recurrence. The dog died due to progressive deterioration 22 months after the initial presentation. Post-mortem examination revealed focally extensive necrosis with marked calcification in the parenchyma of the adrenal glands and regeneration of the cells in the zona fasciculata with severe fibrosis. Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound can support the diagnosis of adrenal necrosis and hypoadrenocorticism.

Contact allergy to corticosteroids: Is the European baseline series sufficient?

BACKGROUND: Patients are consecutively screened for contact allergy to corticosteroids with budesonide and tixocortol-21-pivalate in the European baseline series. Centres using TRUE Test also include hydrocortisone-17-butyrate. A supplementary corticosteroid patch test series is used in case of suspicion of corticosteroid contact allergy or when a marker of corticosteroid contact allergy is positive. OBJECTIVE: The aims were to evaluate (1) the efficacy of corticosteroids in the TRUE Test and (2) co-sensitization patterns. METHODS: This retrospective study analysed patients patch tested with TRUE Test corticosteroids plus supplementary corticosteroid series in the period 2006-2020 at the Department of Dermatology and Allergy Centre, Odense University Hospital. RESULTS: Of 1852 patients tested, 119 were sensitised to TRUE Test corticosteroids and supplementary testing found additional reactions to other corticosteroids in 19 of 119 patients. TRUE Test corticosteroids gave more positive and stronger reactions compared to allergens in petrolatum/ethanol. Fourteen percent of sensitised patients were co-sensitised to multiple corticosteroid groups. Baeck group 3 corticosteroids accounted for 9 of 16 patients not identified by TRUE Test. CONCLUSIONS: Budesonide, hydrocortisone-17-butyrate, and tixocortol-21-pivalate in combination are sensitive corticosteroid markers. In case of clinical suspicion of corticosteroid contact allergy, patch testing with supplementary corticosteroids is highly recommended.

The Timing of Initiating Hydrocortisone and Long-term Mortality in Septic Shock.

BACKGROUND: Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced conflicting results. We performed a retrospective review of a large administrative database of intensive care unit (ICU) patients to evaluate the association between the timing of hydrocortisone initiation and short- and long-term mortality in septic shock. We hypothesized that a longer duration between the first vasopressor use for sepsis and steroid initiation was associated with increased mortality. METHODS: Data were extracted from the Medical Information Mart in the Intensive Care-IV database. We included adults who met Sepsis-3 definition for septic shock and received hydrocortisone. The exposure of interest was the time in hours from vasopressor use to hydrocortisone initiation (>12 as late and ≤12 as early). The primary outcome was 1-year mortality. Secondary outcomes included 28-day mortality, 90-day mortality, in-hospital mortality, and length of hospital stay. Cox proportional hazard models were used to estimate the association between exposure and mortality. Competing risk regression models were used to evaluate the association between exposure and length of hospital stay. RESULTS: A total of 844 patients were included in this cohort: 553 in the early group and 291 in the late group. The median time to hydrocortisone initiation was 7 hours (interquartile range, 2.0-19.0 hours). After multivariable Cox proportional hazard analysis, we found that hydrocortisone initiation >12 hours after vasopressor use was associated with increased 1-year mortality when compared with initiation <12 hours (adjusted hazard ratio, 1.39; 95% confidence interval, 1.13-1.71; P = .002, E-value = 2.13). Hydrocortisone initiation >12 hours was also associated with increased 28-day, 90-day, and in-hospital mortality and prolonged length of hospital stay. CONCLUSIONS: In patients with septic shock, initiating hydrocortisone >12 hours after vasopressor use was associated with an increased risk of both short-term and long-term mortality, and a prolonged length of hospital stay.

Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Factitious, or iatrogenic but unexpected Cushing's syndrome.

Prolonged exposition to supraphysiological doses of exogenous glucocorticoid eventually results in iatrogenic Cushing's syndrome, whose intensity depends on the dose and duration of the treatment and on individual susceptibility. In patients with chronic inflammatory diseases treated with oral glucocorticoids iatrogenic Cushing's is expected and recognized and it only imposes that the dose of glucocorticoid be maintained as low as possible and that there is no better alternative therapy available.In some cases, however, iatrogenic Cushing's syndrome may be unexpected by the prescribing physician as the true exposure to corticoids may depend largely on the patient: this is the case for topical steroids used in inflammatory skin diseases such as psoriasis. Factitious Cushing's syndrome (FCS) is another cause of exogenous Cushing's syndrome in whom the exposure to glucocorticoid is unexpected, as it is hidden to the physician by a patient suffering from Münchausen syndrome. FCS might be very difficult to diagnose depending on the type of glucocorticoid used, the specificity of the dosage used for cortisol, and the timing of the measurement of cortisol and ACTH. The best evidence for FCS is the demonstration by LC-MS/MS of exogenous glucocorticoid in his urine or plasma but this requires that the patient has not stopped to take glucocorticoid at the time of exploration. FCS related to hydrocortisone can be difficult to prove and to distinguish from cyclical Cushing's syndrome. Analysis of the literature shows that FCS has led to prolonged or invasive explorations and even to adrenal surgery, while unrecognized FCS has led to fatal infectious complications.

Pituitary and adrenal disorders induced by immune checkpoint inhibitors.

Over the past decade, the development of ICI (immune checkpoint inhibitors) has constituted a revolution in the treatment of many cancers, but with a specific toxicity profile including endocrine IRAEs (immune-related adverse events). As the indications for these molecules are constantly increasing due to their efficacy, it is important that endocrinologists and oncologists know how to detect, manage and monitor this type of toxicity. Many guidelines and recommendations have been proposed in the last few years for the management of endocrinopathies. French guidelines on immunotherapy-related endocrine IRAEs were published in 2018, with a specific algorithm for hypophysitis and primary adrenal insufficiency (PAI), based on clinical suspicion followed by biochemical and imaging evaluation, and are still relevant today. Here we present the general pathophysiological mechanisms of these toxicities, and discuss the incidence, diagnosis, treatment, progression, management and monitoring of pituitary and adrenal disorders in patients treated by immunotherapy, with emphasis on hypophysitis, which is much more frequent than PAI with this type of molecule. We also highlight several key points, such as the need for emergency treatment by hydrocortisone with the possibility of continuing immunotherapy in these endocrinopathies, and the long-term persistence of corticotropin or adrenal deficiency in most cases, requiring specific "hydrocortisone education". These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review.

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.

Short-term pulmonary and systemic effects of hydrocortisone initiated 7-14 days after birth in ventilated very preterm infants: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week. DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models. RESULTS: Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH2O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure. CONCLUSIONS: Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).

Hydrocortisone-induced blood pressure reduction in a patient with anterior pituitary hypofunction: a case report.

Hydrocortisone is widely used for the anti-inflammatory and immunosuppressive effects and physiological substitute of endogenous glucocorticoid. Allergic reaction to hydrocortisone is infrequent, but once it occurs, it can affect the disease profile or survival of patients. The present study reported a case of hydrocortisone-induced blood pressure reduction in a patient with anterior pituitary hypofunction due to allergic reaction. The patient was admitted with burns. Anterior pituitary hypofunction was diagnosed during hospitalisation owing to persistent hyponatremia. During hydrocortisone intravenous administration, blood pressure was decreased to 70/40 mmHg, accompanied with flushed face and vasodilation. According to World Health Organization Uppsala Monitoring Centre (WHO-UMC) causality assessment and Naranjo scale, there was a probable relationship of reduced blood pressure with hydrocortisone. To the best of our knowledge, we have presented the first case of an anaphylaxis reaction of blood pressure reduction following hydrocortisone administration in the anterior pituitary hypofunction patient.

Hydrocortisone-induced symptomatic sinus bradycardia.

Steroids are commonly prescribed medications that have a wide range of adverse effects. Bradycardia is one of the rare but significant side effects of steroid use, and only a few cases have been reported with bradycardia as a side effect. In this report, we present a case of a woman in her early 50s who developed severe symptomatic sinus bradycardia following high-dose administration of intravenous hydrocortisone, initiated for acute exacerbation of Crohn's disease. Her symptoms entirely resolved after discontinuation of the steroid. This case highlights the importance of obtaining baseline ECG and cardiac monitoring in patients treated with pulsed high-dose steroids.

Tolerance of hydrocortisone prophylaxis administration in extreme preterm neonates: Experience of a single UK level III neonatal unit.

OBJECTIVE: To assess the safety of the routine use of low-dose prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia (BPD) in infants born <28 weeks' gestation. DESIGN: A single-centre retrospective cohort study of infants born <28 weeks, before and after hydrocortisone implementation. Data was collected from electronic patient records and compared between both groups. MAIN OUTCOME MEASURES: The incidence of serious adverse events associated with hydrocortisone use was measured in each group. The rates of spontaneous intestinal perforation (SIP), late onset sepsis (LOS). Necrotising enterocolitis (NEC) and BPD were compared. RESULTS: There were 88 infants in the pre-hydrocortisone group and 103 infants in the hydrocortisone group. In comparison to the pre-hydrocortisone group, the incidence of SIP in the hydrocortisone group was 7.7 % (vs 3.4 % p = 0.2), NEC 30 % (vs 25 % p = 0.43) and LOS 34 % (vs 30.6 % p = 0.63) Rates of BPD in the hydrocortisone group were 59 % (vs 52.2 % p = 0.33) mortality 18.4 % (vs 20.4 % p = 0.73) and BPD free survival 26.2 % (vs 27.2 % p = 0.87). Infants who received hydrocortisone had a significantly lower requirement of inotropic support of 32 % vs 48.3 % (p = 0.02). Results remained unchanged after logistic regression analyses for potential confounding factors (ethnicity, chorioamnionitis, multiple pregnancy and antenatal steroids). CONCLUSION: Prophylactic administration of low-dose hydrocortisone for BPD to infants born below 28 weeks' gestation was not associated with an increase in serious adverse outcomes in our population.

Management of Acute Adrenal Insufficiency-Related Adverse Events in Children with Congenital Adrenal Hyperplasia: Results of an International Survey of Specialist Centres.

INTRODUCTION: There is wide variation in reported rates of acute adrenal insufficiency (AI)-related adverse events (sick day episodes and adrenal crises) between centres. This study aimed to evaluate the level of consensus on criteria considered essential for defining and managing these events in children with Congenital Adrenal Hyperplasia. METHODS: Active users of the International Congenital Adrenal Hyperplasia and International Disorders of Sex Development (I-CAH/I-DSD) Registries (n = 66), non-active users of I-CAH/I-DSD (n = 35), and the EuRRECa e-Reporting Registry (n = 10) were approached to complete an online survey. RESULTS: Fifty-six centres from 27 countries responded to the survey; the response rates for the three groups were 42 (65%), 11 (31%), and 3 (30%), respectively. Steroid management plans, one to one patient education, and contact details of health care staff were provided by over 90% of centres in high-income countries. All 56 centres advised glucocorticoid stress dosing in the event of fever. Less common indications for sick day dosing included vaccination and mild afebrile intercurrent illness, recommended by 17 (30%) and 9 (16%) centres, respectively. The most frequently reported stress dosing regimens were tripling the total daily dose of hydrocortisone and administering 3 times daily and doubling or tripling the largest daily hydrocortisone dose depending on the nature of the trigger and administering 3 times daily, recommended by 24 (43%) and 21 (38%) centres, respectively. Vomiting was the most common indication for intramuscular hydrocortisone injection, reported by 34 (61%) centres. Over 50% of respondents indicated that essential clinical criteria for adrenal crisis should include fatigue and nausea or vomiting and over 60% indicated that hypotension, hyponatraemia, hyperkalaemia, and clinical improvement following parenteral glucocorticoids were essential criteria. In the event of an adrenal crisis, 47 (84%) reported that the majority of patients were admitted to hospital. For the management of an adrenal crisis, a bolus parenteral injection of hydrocortisone was the most frequently administered medication, reported by 50 (89%) centres. CONCLUSION: Although there is variation in the definition and management of AI-related adverse events in children amongst centres, there is also a good level of consensus on specific aspects that can lead to greater benchmarking of care.