ABSTRACT
Context Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.
Objective To estimate infection risk in PAI due to Addison’s disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.
Design Retrospective cohort study using UK data collected from 1995 to 2018.
Main outcome measures Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls.
Results A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval 1.64-2.69], CAH 3.23 [1.21-8.61]), UTIs (AD 1.51 [1.29-1.77], CAH 2.20 [1.43-3.34]), and GIIs (AD 3.80 [2.99-4.84], CAH 1.93 [1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [1.69-1.77], CAH 1.77 [1.66-1.89]) and antifungals (AD 1.89 [1.74-2.05], CAH 1.91 [1.50-2.43]).
Conclusions There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.
Précis Using data from 1580 AD patients and 602 CAH patients collected in a UK primary care database from 1995 to 2018, we identified increased risk of infections and antimicrobial prescription counts.
Footnotes
↵* joint senior authors
Funding: This work was supported by the Medical Research Council UK (Program Grant 0900567, to W A). K.N. is a UK Research and Innovation (UKRI)/Health Data Research (HDR) UK Innovation Clinical Fellow. W.A. receives support from the National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care UK.
Disclosure Statement: W.A. serves as scientific consultant to Diurnal Ltd. and Spruce Biosciences Inc. All other authors have no conflict of interest to declare.
Additional analyses (patients with at least two prescriptions of gluco-and mineralocorticoids and patients with AD and type1 diabetes mellitus) and appendix list with read codes for AD and CAH diagnosis, corticosteroid replacement therapy and diagnoses of infections.