Increased mortality in primary adrenal insufficiency: a systematic review and meta-analysis

Objective Despite important advances in the management of primary adrenal insufficiency (PAI), prognosis in these patients remains poor. Data on mortality in PAI has not been entirely consistent, and to date, no systematic synthesis has been performed. The aim of this study was to conduct a systematic review and a meta-analysis to synthesize available evidence on mortality in adult patients with PAI including congenital adrenal hyperplasia (CAH). Design This is a systematic review and meta-analysis. Methods Medline, Cochrane CENTRAL, Web of Science, and Embase databases were searched for studies on mortality in PAI. The results were screened by 2 reviewers by titles and abstracts, and selected articles were subsequently reviewed in full text. Observational studies on mortality compared to a reference population were included. Results Out of the 6238 reports identified, 9 reports were included in the systematic review, with a total population of 13 969 patients. Two of the 9 studies included overlapping population; therefore, only 7 studies were included in the meta-analysis (9876 patients). Four studies assessed mortality utilizing hazard ratio (HR) with a pooled HR of 2.51 (95% confidence interval [CI] 1.47-4.31, I2 = 86.1%); 3 studies used standardized mortality ratio (SMR) with a pooled SMR of 2.49 (95% CI 0.99-6.28, I2 = 97.9%). The main cause of death was cardiovascular disease. A sub-analysis of patients with CAH showed a pooled HR of 2.88 (95% CI 1.38-6.01, I2 = 90.3%), with the main cause of death being adrenal crisis. Conclusions Mortality in patients with PAI was increased 2.5-fold compared to the reference population.