Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Population pharmacodynamic modeling of intramuscular and oral dexamethasone and betamethasone effects on six biomarkers with circadian complexities in Indian women.

Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and betamethasone (BET) in 48 healthy nonpregnant Indian women in a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM) where each woman enrolled in a two-period cross-over study. Plasma concentrations collected over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Overall, BET exhibited slower clearance, similar volume of distribution, faster absorption, and longer persistence than DEX with BET acetate producing extremely slow absorption but full bioavailability of BET. Six biomarkers were assessed over a 24-h baseline period with four showing circadian rhythms with complex baselines. These baselines and the strong responses seen after drug dosing were fitted with various indirect response models using the Laplace estimation methods in NONMEM 7.4. Both the PK and six biomarker responses were well-described with modest variability likely due to the homogeneous ages, weights, and ethnicities of the women. The drugs either inhibited or stimulated the influx processes with some models requiring joint inclusion of drug effects on circadian cortisol suppression. The biomarkers and order of sensitivity (lowest IC50/SC50 to highest) were: cortisol, T-helper cells, basophils, glucose, neutrophils, and T-cytotoxic cells. DEX sensitivities were generally greater than BET with corresponding mean ratios for these biomarkers of 2.86, 1.27, 1.72, 1.27, 2.69, and 1.06. Overall, the longer PK (e.g. half-life) of BET, but lesser PD activity (e.g. higher IC50), produces single-dose response profiles that appear quite similar, except for the extended effects from BET-PA. This comprehensive population modeling effort provides the first detailed comparison of the PK profiles and six biomarker responses of five commonly used dosage forms of DEX and BET in healthy women.

Fifteen-minute consultation: An approach to the child receiving glucocorticoids.

Glucocorticoids (GC) are used in paediatric practice for a broad range of conditions and all paediatricians will prescribe GC, in some form, during their career. A wide variety of GC formulations, doses and administration routes are used for periods of time ranging from days to years. Exposure to exogenous GC can result in hypothalamic-pituitary-adrenal axis suppression-otherwise known as adrenal suppression (AS). Patients with AS may be well most of the time but if GC therapy is reduced or stopped or if additional endogenous GC cannot be generated during illness, then an absolute or relative lack of GC can result in severe illness or death. Here, we highlight the relevance of AS to all paediatricians by providing an overview of the background and discussing the presentation and approaches to the management of this clinical entity.

Adrenal suppression from exogenous glucocorticoids: Recognizing risk factors and preventing morbidity.

Adrenal suppression (AS), a potential side effect of glucocorticoid therapy (including inhaled corticosteroids), can be associated with significant morbidity and even death. In Canada, adrenal crisis secondary to AS continues to be reported in children. Being aware of symptoms associated with AS, understanding the risk factors for developing this condition, and familiarity with potential strategies to reduce risks associated with AS, are essential starting points for any clinician prescribing glucocorticoids.

Evidence of Systemic Absorption of Enteral Budesonide in Patients with Fontan-Associated Protein-Losing Enteropathy.

To evaluate for evidence of systemic glucocorticoid absorption in cases of Fontan-associated protein-losing enteropathy (PLE) treated with enteral budesonide, we reviewed the charts of 27 patients with Fontan-associated PLE followed at Children's Hospital Colorado from 2005 to 2018. Cases were excluded for lack of budesonide thserapy or a treatment duration of less than 6 months. Charts were examined by two endocrinologists for review of prior biochemical endocrine evaluations, alterations in linear growth, and physical exam findings consistent with steroid excess. Twelve patients met inclusion criteria. Eight had prior documented cortisol screening. Three patients were tested while on treatment with a median fasting AM cortisol of 0.9 mcg/dL; two of these had a concomitantly measured ACTH, both below the detectable limit. Five patients were tested while weaning or having discontinued budesonide, with a median fasting AM cortisol of 9.1 mcg/dL. Eleven patients had decreases in height velocity associated with starting budesonide. Six patients had documentation of cushingoid features by an endocrinologist. In this cohort of children treated with budesonide for PLE following Fontan, clinical signs of systemic glucocorticoid absorption were frequent. Cortisol secretion was suppressed while on therapy, with adrenal recovery noted once budesonide was discontinued. Growth failure and cushingoid features were common findings. While these findings should be confirmed in larger cohorts, we recommend that the evaluation for systemic absorption of exogenous steroids be considered in patients treated with long-term enteral budesonide given the potential risk for adrenal crisis in times of physiologic stressors.

Screening practices for paediatric asymptomatic adrenal suppression in Canada: Are we addressing this important risk?

BACKGROUND: Children with adrenal suppression (AS), a potential side effect of glucocorticoids (GCs) may be asymptomatic, present with nonspecific signs and symptoms or with adrenal crisis. Asymptomatic AS (AAS) can only be diagnosed through screening. Identifying and treating asymptomatic patients before symptoms develop may reduce morbidity. Screening guidelines for AS are lacking. Consequently, screening practices are highly variable. OBJECTIVE: To assess (1) the screening practices for and recognition of paediatric AAS among clinicians in Canada and (2) the educational impact of a 2-year surveillance program of symptomatic AS cases. METHODS: Before and after a 2-year Canadian Paediatric Surveillance Program (CPSP) study of symptomatic AS, participants were surveyed through the CPSP. The prestudy survey was sent to 2,548 participants in March 2010 and the poststudy survey was sent to 2,465 participants in April 2013. RESULTS: Response rates were 32% for the prestudy survey and 21% for the poststudy survey. Between the pre- and poststudy surveys, the percentage of physicians who reported routinely screening patients on GCs for AS increased from 10% to 21% and the percentage who reported having a screening policy in their office/centre increased from 6% to 11%. There was no significant change in the percentage of physicians who had diagnosed a child/youth with AAS in the preceding year. CONCLUSION: Frequency of screening for AAS increased following the 2-year study but remains low. Development of a clinical practice guideline should increase both awareness of asymptomatic AS among Canadian paediatricians and the identification of AAS, before symptoms develop.

Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. However adverse effects of ICS on Hypothalamo Pituitary Adrenal (HPA) axis, growth and bone metabolism are a concern. Hence the primary objective of this study was to describe the effects of long term inhaled corticosteroid therapy (ICS) on adrenal function, growth and bone health in children with asthma in comparison to an age and sex matched group of children with asthma who were not on long term ICS. Describing the association between the dose of ICS and duration of therapy on the above parameters were secondary objectives. METHOD: Seventy children with asthma on ICS and 70 controls were studied. Diagnosis of asthma in selected patients was reviewed according to the criteria laid down by GINA 2018 guidelines. The estimated adult heights were interpreted relative to their Mid Parental Height (MPH) range. Serum calcium, alkaline phosphatase and vitamin D levels were analyzed in both groups and cortisol value at 30 min following a low dose short synacthen test was obtained from the study group. The average daily dose of ICS (Beclamethasone) was categorized as low, medium and high (100-200, 200-400, > 400 µg /day) respectively according to published literature. RESULTS: Heights of all children were within the MPH range. There was no statistically significant difference in the bone profiles and vitamin D levels between the two groups (Ca: p = 0.554, vitamin D: p = 0.187) but vitamin D levels were insufficient (< 50 nmol/l) in 34% of cases and 41% of controls. Suppressed cortisol levels were seen in 24%. Doses of ICS were low, medium and high in 56, 32 and 12% of children respectively. The association between adrenal suppression with longer duration of therapy (p < 0.01) and with increasing dose of ICS (p < 0.001) were statistically significant. CONCLUSION: ICS had no impact on the growth and bone profiles but its dose and duration were significantly associated with adrenal suppression.

Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects.

Part 2 of this 4-part continuing medical education series continues with a discussion of the prevention and management of gastrointestinal side effects associated with corticosteroid use, including peptic ulcer disease, gastrointestinal bleeding, and pancreatitis, followed by a review of corticosteroid-related endocrinologic side effects, such as diabetes, adrenal suppression, and Cushing syndrome.

Inhaled corticosteroid related adrenal suppression detected by poor growth and reversed with ciclesonide.

INTRODUCTION: This case series intends to highlight the association between decreased linear growth velocity and adrenal suppression in patients receiving inhaled corticosteroids for asthma. A potential treatment option is also discussed. Adrenal suppression secondary to inhaled corticosteroids has previously been reported and is often underrecognized. A decrease in linear height velocity has also been associated with inhaled corticosteroids. However, a decrease in height velocity has not been shown to predict adrenal suppression. CASE STUDY: This case series of 15 patients receiving inhaled corticosteroids for control of asthma were noted to have a decrease in linear growth velocity ultimately associated with adrenal suppression. A change in inhaled corticosteroid to ciclesonide led to recovery of adrenal function without impacting asthma control. RESULTS: Chart review from a pediatric pulmonology clinic was performed. Growth parameters and laboratory studies were recorded and analyzed. A mean decrease in height standard deviation score in the year prior to diagnosis of adrenal suppression was -0.59, -0.11, and -0.18, in pre-puberty, peri-puberty, and post-puberty patients, respectively. After ciclesonide therapy was initiated, a mean change in height standard deviation score of +0.40, +0.13, and -0.13, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively. A change in growth velocity of +5.3 cm/yr, +2.1 cm/yr, and -1.9 cm/yr, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively, after starting ciclesonide. CONCLUSIONS: Height velocity should be monitored closely during routine asthma visits to identify potential adrenal suppression associated with inhaled corticosteroids use. Ciclesonide is a good option for asthma treatment that allows for adrenal recovery.

Maternal use of prednisolone is unlikely to be associated with neonatal adrenal suppression-a single-center study of 16 cases.

The use of supra-physiological, exogenous corticosteroids in pregnancy may lead to neonatal adrenal suppression. We report on a single-center, case series study carried out between 2006 and 2014, which included all newborns (n = 16) of mothers using prednisolone ≥10 mg/day during pregnancy. Newborns were routinely assessed according to hospital protocol, with follow-up until 6 weeks after birth. We investigated the clinical symptoms and biochemical findings of adrenal suppression occurring in the newborns. Mean dose of maternal prednisolone was 29.7 ± 16.1 mg/day with a mean duration of 18.4 ± 15.4 weeks. Five newborns showed hypoglycemia with normal serum cortisol concentrations and urinary steroid profiles. Two newborns had abnormal urinary steroid profiles, probably the result of prematurity, but with adequate adrenal stress response during clinical sepsis. CONCLUSION: In this retrospective case series, we found no evidence of prolonged effects of maternal prednisolone use during pregnancy on the neonatal hypothalamic-pituitary-adrenal axis. What is known: • The use of prednisolone during pregnancy may cause increased steroid levels in the fetus by partially passing through the placenta. • So far, there was very limited data available on the occurrence of adrenal suppression in the newborn of mothers using prednisolone during pregnancy. What is new: • The use of high-dosage prednisolone during pregnancy for ≥1 week (mean duration of 18.4 ± 15.4 weeks), prior to delivery, appears to have little influence on the neonatal hypothalamic-pituitary-adrenal axis.

Etomidate derivatives: Novel pharmaceutical agents in anesthesia.

Etomidate is an imidazole derivative that possesses important sedative properties employed in anesthesia practice, however, etomidate has a number of well-know side effects which limit its use in certain subpopulations and over long periods of time, mostly related to dose-dependent adrenal suppression. This review focuses on novel etomidate derivatives with an emphasis on pharmacological properties which afford improved safety profile and potentially desirable clinical effects. The pharmacology and clinical investigation of some of these etomidate derivatives, e.g. cyclopropyl-methoxycarbonyl, carboetomidate metomidate, methoxycarbonyl-etomidate, cyclopropyl-methoxycarbonyl metomidate (CPMM), and dimethyl-methoxycarbonyl metomidate, are discussed in detail. The increased potency and decreased metabolite build-up of CPMM potentially makes it a very favorable drug, particularly in the setting of prolonged infusions. Further, when compared with etomidate, CPMM produces lower plasma cytokine concentration and improved survival in lipopolysaccharide inflammatory sepsis models.

Stress Dose Steroids: Myths and Perioperative Medicine.

Perioperative medication management for patients with systemic autoimmune inflammatory diseases has focused on strategies to improve outcomes and mitigate risks. The emphasis has been to minimize the risk of infection associated with most antirheumatic medications, while attempting to avoid flares of disease precipitated by medication withdrawal. Management of glucocorticoids in the perioperative period has been based on an assumption that supraphysiologic increases in dose were always necessary to avoid hypotension and shock in glucocorticoid treated patients, and alternative strategies were rarely considered despite the known infectious, metabolic, and wound healing risks associated with glucocorticoid administration. This paper will review current recommendations for perioperative glucocorticoid administration for glucocorticoid treated patients with systemic inflammatory autoimmune diseases and discuss glucocorticoid physiology to analyze the basis for these recommendations and consider alternative perioperative management strategies.

Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study.

BACKGROUND: Cortisol is a hormone involved in many physiological functions including fetal maturation and epigenetic programming during pregnancy. This study aimed to use hair cortisol as a biomarker of chronic inhaled corticosteroid (ICS) exposure and assess the potential effects of asthma on the hypothalamic-pituitary-adrenal (HPA) axis in pregnant women. We hypothesized that pregnant women with asthma treated with ICS would exhibit lower hair cortisol concentrations, indicative of adrenal suppression, compared to women with asthma not using ICS and women who do not have asthma. METHODS: We performed an observational retrospective cohort study. Hair samples were analyzed from pregnant women with asthma, with (n = 56) and without (n = 31) ICS treatment, and pregnant women without asthma (n = 31). Hair samples were segmented based on the growth rate of 1 cm/month and analyzed by enzyme immunoassay to provide cortisol concentrations corresponding to preconception, trimesters 1-3, and postpartum. Hair cortisol concentrations were compared within and among the groups using non-parametric statistical tests. RESULTS: Hair cortisol concentrations increased across trimesters for all three groups, but this increase was dampened in women with asthma (P = 0.03 for Controls vs. ICS Treated and Controls vs. No ICS). ICS Treated women taking more than five doses per week had hair cortisol concentrations 47 % lower in third trimester than Controls. Linear regression of the third trimester hair cortisol results identified asthma as a significant factor when comparing consistent ICS use or asthma as the predictor (F(1, 25) = 9.7, P = 0.005, R(2) adj = 0.257). CONCLUSIONS: Hair cortisol successfully showed the expected change in cortisol over the course of pregnancy and may be a useful biomarker of HPA axis function in pregnant women with asthma. The potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remains to be determined.

Effects of etomidate on adrenal suppression: a review of intubated septic patients.

BACKGROUND: Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients are at an increased risk of independently developing adrenal suppression, which has been associated with increased mortality in some studies. Since etomidate affects cortisol production, its use in septic patients is controversial. However, data are still lacking to prove that etomidate should be avoided in this patient population. OBJECTIVES: The objective was to review patients diagnosed with sepsis who received etomidate during RSI. Our hypothesis is that patients who receive etomidate will experience clinically significant hypotension within the first 24 hours of intubation. METHODS: A retrospective cohort study was conducted on patients intubated in the emergency department (ED) and medical/surgical floors at our institution from 2004 to 2010. Once patients with a diagnosis of sepsis were identified, it was determined whether the patients received etomidate or a different sedative during intubation. The primary endpoint was clinically significant hypotension: systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg. RESULTS: One hundred fifty-seven patients, 110 etomidate and 47 non-etomidate, were included in the final analysis. Hypotension was seen in 79 (71.8%) patients who received etomidate and in 14 (29.8%) patients who received another sedative (P ≤ .001). There were no statistically significant differences in secondary objectives. CONCLUSION: Etomidate use for induction of anesthesia during RSI was associated with clinically significant hypotension when compared to other sedatives. The hypotension was transient and did not translate into statistically significant differences in the secondary clinical endpoints.

Dexamethasone alleviates etomidate-induced myoclonus by reversing the inhibition of excitatory amino acid transporters.

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

Adrenal suppression from vamorolone and prednisone in Duchenne muscular dystrophy: results from the phase 2b clinical trial.

CONTEXT: Vamorolone, a novel "dissociative" steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD). OBJECTIVES: To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD, and to assess cortisol thresholds using a monoclonal antibody immunoassay. METHODS: Post-hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of <500nmol/L ("historical threshold") and <400nmol/L ("revised threshold"). RESULTS: Mean age at enrolment was 5.41±0.86 years (N=118). At Week 24, proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day=100% (25/25) and 92.0% (23/25); vamorolone 6 mg/kg/day=95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day=84.2% (16/19) and 47.5% (9/19); and placebo=20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48=0.83). CONCLUSIONS: AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone.

Long-Term Usage of Oral Glucocorticoids Leading to Adrenal Insufficiency: A Comprehensive Review of the Literature.

Systemic glucocorticoid therapy is used worldwide by one to three percent of the general population and 0.5-1.8% on long-term oral glucocorticoid use. It is widely used in conditions such as inflammation, autoimmune diseases, and cancer to inhibit inflammatory responses. One of the possible undesirable side effects of exogenous corticosteroid treatment is adrenal suppression upon discontinuation of the medication and adrenal insufficiency after utilizing the supraphysiologic doses for more than one month. To prevent patients from the unwanted signs and symptoms of adrenal insufficiency, including fatigue, gastrointestinal upset, anorexia/weight loss, etc., better management of the quantity and frequency of exogenous corticosteroid use, as well as better education before starting its use, is needed. For patients actively on exogenous corticosteroids, a close follow-up must be in place to avoid adrenal suppression after the eventual discontinuation of their use. This review article summarizes the important studies to date on this subject, especially oral glucocorticoid use, and analyzes risks such as dose, duration of exposure, and comorbidities of adrenal insufficiency associated with oral glucocorticoid use. We comprehensively include information on those with primary adrenal insufficiency and pediatric patients, hoping to provide better insight and clinical reference.

Topical Corticosteroid-Induced Adrenal Insufficiency: A Case Report.

Topical Corticosteroids (TCS) are the most commonly prescribed medications in Dermatology practice. They are considered safe and effective if used at the appropriate location and for the appropriate duration. Local side effects due to TCS are not uncommon. However, systemic side effects are rare. Herein, we present a patient who developed adrenal insufficiency secondary to the use of TCS.

Hypothalamic-pituitary-adrenal axis suppression and intranasal corticosteroid use: A systematic review and meta-analysis.

BACKGROUND: Intranasal corticosteroids (INCS) are used in the management of sinonasal conditions. Use of exogenous steroids can be associated with hypothalamic-pituitary-adrenal axis dysfunction and adrenal insufficiency (AI). We aimed to estimate the rate of AI after INCS use in a meta-analysis, stratified by steroid type and treatment duration. METHODS: Ovid Medline, Embase Classic, PubMed, Web of Science, and CINAHL databases were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies investigating INCS use and AI. AI was defined as morning serum cortisol <550 nmol/L and <80 nmol/L with and without adrenocorticotropic hormone stimulation. INCS were classified as first (beclomethasone dipropionate, triamcinolone acetonide, beclomethasone, budesonide, dexamethasone) and second (ciclesonide, mometasone furoate, and fluticasone propionate) generation. Duration of treatment was classified as short (<1 month), medium (1-12 months), and long-term (>12 months) time periods. RESULTS: This search identified 3668 articles. A total of 39 studies (1678 patients) were included in the final analysis. The pooled percentage of AI for routinely utilized first- and second-generation INCS was 0.70% (95% confidence interval [CI], 0.29-1.12%). Stratified by type, AI was observed in 0.78% (95% CI, 0.25-1.30%) of first-generation and 0.58% (95% CI, -0.1% to 1.26%) of second-generation steroids. AI was seen in 0.48% (95% CI, -0.01% to 0.96%) of short-term, 1.13% (95% CI, 0.2-2.1%) of medium-term, and 1.67% (95% CI, 0.37-2.9%) of long-term use of INCS. CONCLUSION: Overall, the use of INCS carries a low risk for AI. Although modest, this risk may differ depending on the length of duration and type of INCS used. Informing patients of these risks is of importance for the treatment of chronic sinonasal conditions.