Endocrine Abstracts

JOINT1946

Introduction: Primary adrenal insufficiency (PAI) is mainly due to autoimmune adrenalitis in developed countries and the most common inherited form is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. There is controversy on long-term outcomes in PAI, with earlier studies showing that mortality was not different from the general population and more recent studies showing higher mortality. The primary aim of this study is therefore to synthetise the evidence on long-term mortality in PAI. The secondary aims are to analyse mortality due to cardiovascular and infectious diseases, along with time trends in mortality.

Methods: A database search of Medline, Cochrane, Embase and Web of Science was conducted for studies on mortality in PAI, including CAH. Two reviewers conducted an initial screening of the titles and abstracts. Thereafter, each reviewer examined the selected articles in full text. Observational studies reporting all-cause mortality in comparison with a control group or general population were included. The extracted data was systematically synthetised. The study quality was assessed independently by two reviewers, following the Newcastle-Ottawa quality assessment scale. The protocol for this systematic review complies with the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines and was registered in PROSPERO (CRD42023416253)¹.

Results: Totally, 5463 articles were identified. After title and abstract screening, 54 articles were reviewed in full text and nine were included in the systematic review. Cardiovascular disease, infections, neoplasms and adrenal crises were the most common causes of death. Of the nine studies, two were removed due to overlapping population. The meta-analysis included therefore 7 studies and in total 10211 patients (6178 with autoimmune PAI and 4033 with CAH). Four studies were cohort studies (6085 patients), assessing mortality using hazard ratios (HR), with a pooled HR of 2.51, 95% CI: 1.47–4.31, I²=86.1%. Three studies were population-based (4126 patients) that assessed mortality using standardised mortality ratios (SMR), with a pooled SMR of 2.49, 95% CI: 0.99–6.28, I² =97.9%. Cause-specific mortality and time-trend analyses were not performed due to lack of data or small sample size.

Conclusions: This is the first systematic review and meta-analysis studying mortality in patients with PAI. The analysis shows a 2.5 times higher mortality among patients with PAI compared to controls or general population.

Reference:

1. Allosso F, Dalakas K, Bergthorsdottir R, Chantzichristos D, Hessman E, Nwaru BI, et al. Mortality in patients with adrenal insufficiency: a protocol for a systematic review and meta-analysis. BMJ Open. 2024;14(1):e076582.