ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP188 | DOI: 10.1530/endoabs.63.GP188

Increased risk of infections in Addison's disease and congenital adrenal hyperplasia patients: a longitudinal study based on a United Kingdom primary care database

Alberto S Tresoldi1,2,3, Dana Sumilo4, Mary Perrins4, Konstantinos A Toulis4, Alessandro Prete2,3, Narendra Reddy5, John A Wass6, Krishnarajah Nirantharakumar4 & Wiebke Arlt2,3


1Endocrinology and Medical Andrology Unit, Humanitas Research Hospital, Rozzano (Milan), Italy; 2Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; 3Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; 4Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; 5Department of Diabetes & Endocrinology, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester, UK; 6Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.


Background: Primary adrenal insufficiency (PAI) can be of autoimmune origin (Addison’s disease, AD) or due to inborn disorders of steroidogenesis (congenital adrenal hyperplasia, CAH). Prognosis of patients with PAI has improved considerably after glucocorticoid replacement therapy became available. However, even in recent years, an increased risk of death has been described in both AD and CAH patients. Moreover, even with the current state-of-the-art replacement therapy, PAI patients are at an increased risk of hospital admission for infections. However, the risk of primary-care managed infections is unknown.

Methods: We performed a retrospective longitudinal cohort study to estimate the risk of three specific infections (lower respiratory tract – LRTIs, urinary tract – UTIs, gastrointestinal – GIs) and the antimicrobial prescriptions rate in AD and CAH patients using data from a UK primary care database. Patients with a diagnosis of AD or CAH were compared with randomly matched unexposed patients (1:2 ratio).

Results: A diagnosis of AD and CAH was established in 1580 and 602 patients, respectively. Mean age was 51.7 years for AD patients and 35.4 years for CAH patients. All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone (82%) in AD and prednisolone in CAH (50%). Compared to controls, both AD and CAH patients exposed to glucocorticoids had a significantly increased risk of infection (LRTIs: AD adjusted incidence rate ratio (aIRR) 2.11 [95% confidence interval (CI) 1.64–2.70], CAH aIRR 3.33 [95% CI 1.22–9.11]; UTIs: AD aIRR 1.56 [95% CI 1.34–1.83], CAH aIRR 2.24 [95% CI 1.45–3.46]; GIs: AD aIRR 3.74 [95% CI 2.94–4.76], CAH aIRR 1.94 [95% CI 1.06–3.56]). This increased risk was also confirmed by an increased prescription rate for antibiotics (AD aIRR 1.74 [95% CI 1.70–1.78], CAH aIRR 1.44 [95% CI 1.38–1.50]) and antifungals (AD aIRR 1.85 [95% CI 1.71–2.01], CAH aIRR 1.63 [95% CI 1.38–1.91]) in both GC-exposed cohorts.

Conclusions: In this study we demonstrated for the first time a glucocorticoid-driven increase in LRTIs, UTIs and GI infections in AD and CAH patients in a primary care setting, with concurrently increased antibiotics and antifungal prescription rate. Future studies will need to address whether this increased infection risk could be reduced by more physiological GC replacement modes.