Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia.

Alberto S Tresoldi,Krishnarajah Nirantharakumar,Konstantinos A Toulis,Narendra Reddy,Wiebke Arlt,Alessandro Prete,Dana Sumilo,Mary Perrins,John A H Wass

doi:10.1210/clinem/dgz006

Abstract

ContextMortality 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.ObjectiveTo estimate infection risk in PAI due to Addison’s disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.DesignRetrospective cohort study using UK data collected from 1995 to 2018.Main outcome measuresIncidence 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.ResultsA 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 (CI) 1.64–2.69], CAH 3.23 [95% CI 1.21–8.61]), UTIs (AD 1.51 [95% CI 1.29–1.77], CAH 2.20 [95% CI 1.43–3.34]), and GIIs (AD 3.80 [95% CI 2.99–4.84], CAH 1.93 [95% CI 1.06–3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69–1.77], CAH 1.77 [95% CI 1.66–1.89]) and antifungals (AD 1.89 [95% CI 1.74–2.05], CAH 1.91 [95% CI 1.50–2.43]).ConclusionsThere 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.

Highlights

Context: Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI)
Addison’s disease (AD) and congenital adrenal hyperplasia (CAH) patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of lower respiratory tract infections (LRTIs) (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64–2.69], CAH 3.23 [95% CI 1.21–8.61]), urinary tract infections (UTIs) (AD 1.51 [95% CI 1.29–1.77], CAH 2.20 [95% CI 1.43–3.34]), and gastrointestinal infections (GIIs) (AD 3.80 [95% CI 2.99–4.84], CAH 1.93 [95% CI 1.06–3.52])
Primary adrenal insufficiency (PAI) is a severe and potentially life-threatening condition caused by the failure of the adrenal cortex to produce glucocorticoids and, in most cases, mineralocorticoids, which occurs in the setting of adrenal disease [1]

Summary

Methods

Study design and setting We conducted a population-based, retrospective, open cohort study to determine the infection risk of patients with AD and CAH in the primary care setting. THIN holds data on demographic characteristics, clinical diagnoses, physical measurements, laboratory results and drug prescriptions recorded using a clinical Read code system. Patients registered in THIN have similar age and sex distributions to the general UK population, and, THIN data are well suited for epidemiological studies [9, 10]. Study population and period Our study population consisted of 2 “exposed” cohorts, comprising adult patients (≥18 years old) diagnosed with AD or CAH according to selected Read codes [11, 12]. We randomly selected 2 individuals from a pool of patients matched for age, sex, and GP practice who did not have a Read code consistent with PAI at any point before or during the observation period

Results

Discussion

Conclusion