ECEESPE2025 Rapid Communications Rapid Communications 13: Adrenal and Cardiovascular Endocrinology Part 2 (6 abstracts)
Adrenal aldosterone synthase (CYP11B2) histopathology and its association with disease-induced sudden death
Antero Ylänen 1,2 , Juhani Isojärvi 1 , Antti Virtanen 3 , Helena Leijon 4 , Tiina Vesterinen 4 , Aapo Aro 5 , Heini Huhtala 6 , Eeva Kokko 1 , Ilkka Pörsti 1,2 , Marianna Viukari 7 , Pasi Nevalainen 1,2 & Niina Matikainen 7
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; 3Forensic Medicine Unit, Finnish institute for health and welfare, Helsinki, Finland; 4HUS Diagnostic Center, HUSLAB, Department of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 5Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 6Health Sciences, Faculty of Social Sciences, Tampere University, Helsinki, Finland; 7Endocrinology, Helsinki University Hospital, ENDO-ERN (European Reference Network on Rare Endocrine Conditions) and University of Helsinki, Helsinki, Finland
JOINT502
Background: //tgcqSudden death is a high-priority public health concern, affecting at least 249,500 individuals each year in the European Union. Unidentified cardiovascular risk factors may account for approximately half of sudden deaths, a devastating event with limited preventive tools. We investigated whether adrenal histopathology suggestive of primary aldosteronism could explain part of the risk for disease-induced sudden death (DSD).
Methods: In this cross-sectional study, autopsies and histopathological analyses, including aldosterone synthase staining of adrenal glands, were performed on 403 consecutive individuals who experienced sudden death. These individuals were classified into 258 cases of DSD and 144 deaths caused by trauma, suicide, or intoxication, i.e., non-disease-induced sudden death (nDSD). Histopathological analysis followed the HISTALDO consensus. A four-grade classification of CYP11B2 positivity was used in the analyses with the following categories:1) aldosterone-producing adenomas (APA) or nodules (APN), 2) aldosterone-producing micronodules (APMs) <20, 3) APMs ≥20, or 4) diffuse CYP11B2 positivity. This trial was registered at ClinicalTrials.gov (NCT05446779).
Findings: Adrenal histopathology revealed changes in 31 (7·7%) subjects of the cohort. Of these, the most prevalent findings [25 (6·2%)] were APA or APN, which were associated with myocardial infarction and atherosclerosis at autopsy. Individuals in the DSD group and the subgroup with sudden cardiac death (SCD) were more likely to have APA or APN than individuals in the nDSD group [23 (8·9%) vs. 2 (1·4%), P=0·002; 16 (8·8%) vs. 2 (1·4%), P=0·003, respectively]. Among all study subjects, heart weight, left ventricular wall thickness and the degree of aortic atherosclerosis showed an increasing trend with decreasing CYP11B2 continuity. In logistic regression analyses APA or APN were explanatory factors for DSD (odds ratio [OR] 6·47, 95% confidence interval [CI] 1·40-29·88, P=0·017) and SCD (OR 10·68, 95% CI 2·02-56·43, P=0·005).
Conclusions: Histopathological findings of APA or APN were observed more frequently in DSD and SCD cases than in nDSD cases and emerged as significant independent predictors of sudden death. The presence of APA or APN, along with a reduction in CYP11B2 continuity indicative of potential autonomous aldosterone production, was associated with markers of cardiovascular morbidity at autopsy. Timely diagnosis and effective treatment of PA may help extend the lifespan of individuals with CYP11B2-positive adrenal pathology. However, whether systematic biochemical screening for PA, targeted MRA therapy, or a combination of both should be implemented to reduce the risk of sudden death requires further investigation.
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