Endocrine Abstracts

Objective: Mortality in autoimmune Addison’s disease (AAD) is increased twofold compared to matched populations. Cardiovascular disease (CVD) is the most common cause of death, but little is known of cardiovascular morbidity. Inadequate glucocorticoid replacement has been implicated in the increased risk of CVD, but evidence is lacking. The objective of this study was to examine cardiovascular morbidity and mortality in AAD, and to investigate the effects of glucocorticoid and mineralocorticoid dosing on the CVD-burden.

Methods: A population-based retrospective cohort study conducted in Sweden. The National Patient Register (NPR) and the Prescribed Drug Register (PDR) were used to identify 1500 patients with both an ICD-diagnosis consistent with AAD, and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. 13 758 matched controls were randomly identified in the Register of Population. Patients and controls were collected 1964–2012. Drug prescription patterns were collected 2005–2012. The main outcome was CVD defined as recorded events of ischemic heart disease or cerebrovascular disease in the NPR or the Cause of Death Register. Adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were analyzed using the Cox proportional hazard model. Daily doses of glucocorticoid and mineralocorticoid replacement were estimated using the PDR. Doses were stratified into tertiles to examine dose-dependent risks of CVD.

Results: AAD was associated with a significantly increased risk of CVD (HR 1.62, 95% CI 1.25–2.16). This risk remained after adjusting for diabetes and chronic obstructive pulmonary disease (HR 1.54, 95% CI 1.16–2.04). Incidence rate ratios (IRR) were 1.9 (95% CI 0.95–3.9) for intermediate-dose and 2.1 (95% CI 1.1–4.3) for high-dose glucocorticoid replacement compared to low-dose glucocorticoid replacement. For mineralocorticoids IRR were 1.1 (95% CI 0.53–2.1) for intermediate-dose and 1.4 (95% CI 0.77–2.7) for high-dose replacement.

Conclusion: Cardiovascular morbidity and mortality is increased in AAD. The risk appears to be positively correlated with increasing glucocorticoid replacement doses, but not with mineralocorticoid replacement doses.