Real world estimates of adrenal insufficiency related adverse events in children with congenital adrenal hyperplasia

Background: Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient or clinician reported sick day episodes (SDE) is less clear. Methods: Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analysed to examine the clinical factors associated with SDE and AC. Results: 518 children with a median of 11 children (range 1, 53) per center had 5,388 visits evaluated over a total of 2,300 patient years. The median number of AC and SDE per patient year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1,544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1,105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (p<0.001), respectively and the median AC per patient year was 0 (0, 2.2) vs 0 (0, 3.0) (p=0.43), respectively. Conclusions: The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardise the definition of SDE