Increased Infection Risk in Addison’s Disease and Congenital Adrenal Hyperplasia

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 (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]). 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.

Dealing with COVID-19: Through Endocrinologist’s Eyes

“…Although several studies have reported that AI itself may increase the risk of infection up to eight folds (43), the current evidence does not specifically support the fact that patients with AI are particularly prone to COVID-19. However, several plausible mechanisms are available, which may render patients with AI susceptible to COVID-19.…”

A COVID-19 pneumonia case report of autoimmune polyendocrine syndrome type 1 in Lombardy, Italy: letter to the editor

“…A population-based, retrospective, open cohort study in the United Kingdom from 1995 to 2018 showed that the Addison's disease cohort, compared with matched controls, had a higher risk of infections of the lower respiratory [adjusted incidence rate ratio (aIRR) 2.11; 95% CI 1.64-2.69], urinary (aIRR 1.51; 95% CI 1.29-1.77), and gastrointestinal (aIRR 3.80; 95% CI 2.99-4.84) tracts, leading to increased use of antimicrobial agents in the primary care setting [6]. Interestingly, the same study showed no increased risk of infection in patients with untreated congenital adrenal hyperplasia (CAH), but an increased infection risk in patients treated for CAH, suggesting that nonphysiological delivery of glucocorticoid replacement may represent a risk factor for the development of infections [6].…”

Peripheral blood mononuclear cells preferentially activate 11-oxygenated androgens

“…However, when assessing the effect of age on androgen activation in peripheral tissues, age-related changes in the supply of androgen precursors from circulation need to be considered, in addition to age-dependent changes in the expression of androgen-activating and -inactivating enzymes in the peripheral target tissues of androgen action. While circulating levels of classic androgens significantly decline with age, levels of 11-oxygenated androgens remain constant across adulthood (29,30). Hence, the peripheral activation of 11-oxygenated androgens is favored over the activation of classic androgens not only by the substrate preference of the key androgen activating enzyme AKR1C3, but also by constant high substrate availability across the life span.…”