MON-170 Real World Estimates of Adrenal Insufficiency Related Adverse Events in Children with Congenital Adrenal Hyperplasia: On Behalf of the I-CAH Consortium

Abstract

Background Although congenital adrenal hyperplasia (CAH) is a rare condition, it is the commonest cause of early-onset primary adrenal insufficiency and places the patient at a life-long risk of sick day episodes (SDE) and adrenal crises (AC). Objective To investigate the epidemiology of SDE and AC in an international cohort of patients <18 yrs old with 21-OH deficiency CAH. Methods Multi-level logistic model analysis of data in the International CAH (I-CAH) registry (www.i-cah.org) to examine the clinical associations of SDE, AC, stress-dose days and hospitalisations. Results 518 patients (F, 53%) from 34 centres in 18 countries with a median number of cases per centre of 12 (IQR 1-26), had a total of 5388 reported visits with a median duration of follow-up per patient of 3.1 yrs (IQR 2.5-5.8). Of the 518 patients, 334 (64%) had ≥1 SDE; the median number of SDE per patient year per centre was 1.0 (IQR 0.4-2.2) and the median duration of SDE was 3.0 days (IQR 2.0-5.0). Children between 1-4 yrs and adolescents (15-18 yrs) had a greater risk of SDE [OR 2.02 (95%CI:1.60,2.56) and OR 1.64 (95%CI:1.34,2.02), respectively] and stress-dosing [OR 2.03 (95%CI:1.56,2.60) and OR 1.63 (95%CI:1.32,2.02), respectively] compared to children <1 yr old. Males were more likely to have a SDE [OR 1.40 (95%CI:1.13,1.73) and stress-dosing [OR 1.40 (95%CI:1.12,1.76) than females. An AC was reported in 4% of SDE (62/1544) with 92% of visits associated with hospital admission. Infectious illness was the most frequent associated event and was reported in 72% (1105/1544) of SDE and 47% (29/62) of AC. Males had a higher risk of AC compared to females [OR 1.03 (95%CI:1.03,1.03). Children with salt-wasting CAH were more likely to be hospitalised during a SDE, compared with those with simple-virilising CAH [OR 2.08 (95%CI:0.99,7.91)]. Children receiving glucocorticoid (GC) doses within the hydrocortisone (HC) equivalent dose (ED) of 10-15mg/m2/d were more likely to have SDE [OR 1.66 (95%CI:1.31,2.10), stress-dosing [OR 1.85 (95%CI:1.44,2.37) and AC [OR 1.08 (95%CI:1.08,1.08), p<0.001] than children on HC ED >15mg/m2/day. Similarly, children on HC ED <10mg/m2/d were more likely to have SDE [OR 2.20 (95%CI:1.66,2.90)], stress-dosing [OR 2.37 (95%CI:1.77,3.19)] and AC [OR 8.34 (95%CI:8.33,8.35), p<0.001] than those on higher doses. Children on FC doses between 50-200mcg/day and lower than 50 mcg were less likely to have AC [OR 4.54 (95%CI:4.54,4.55) and OR 8.58 (95%CI:8.57,8.59), respectively] than those on higher doses (>200mcg/day). Oral GC were increased in 74% (1147/1544) of SDE whilst HC injection was administered in 11% (176/1544) of SDE. Conclusions The real-world data within the I-CAH registry are a valuable resource for identifying factors that place a child with CAH at a higher risk of adverse events and can be used in prediction models for calculating individual risk.