Endocrine Abstracts

Background: The crosstalk between the adrenal gland and different fat depots is largely unknown. As primary hyperaldosteronism leads to an increased risk of cardiovascular disease and associated pathologies (glucose intolerance, diabetes, hyperlipidemia), elucidating the interaction between aldosterone producing adenomas (APAs) and different fat depots might help to understand causality and open new diagnostic and treatment strategies.

Methods: Subcutaneous (s.c.) and periadrenal fat was collected from patients with APA (s.c. n=13, periadrenal, n=20) and, as controls, from non-functional adenomas (NFA, s.c. n=7, periadrenal n=5). mRNA was extracted from the samples and RNA sequencing was performed. Patients’ characteristics were collected.

Results: RNA sequencing revealed a high number of differentially regulated genes in s.c. fat samples of patients with APA vs NFA (n= 68 up, n=259 down), in periadrenal samples of patients with APA vs NFA (n= 16 up, n=117 down), and in periadrenal vs s.c. samples of patients with APA (n= 1632 up, n=826 down). Pathway analysis revealed (amongst others): - an upregulation of the pathways ‘Cushing syndrome’ (enrichment score (ES) 0.6), ‘aldosterone synthesis and secretion’ (ES 0.6) and ‘cortisol synthesis and secretion’ (ES 0.7) in APA periadrenal vs APA s.c\. - an upregulation of the pathways ‘steroid hormone biosynthesis’ (ES 0.5), ‘Cushing syndrome’ (ES 0.4) and ‘cortisol synthesis and secretion’ (ES 0.6) in APA periadrenal vs NFA periadrenal. - an upregulation of the pathways ‘steroid hormone biosynthesis’ (ES 0.5), and a downregulation of ‘cortisol synthesis and secretion’ (ES -0.6) and ‘aldosterone synthesis and secretion’ (ES -0.5) in APA s.c. vs NFA s.c.

Conclusion: RNA sequencing revealed a high number of differentially regulated pathways and genes in s.c. and periadrenal fat depots of patients with APA in comparison to patients with NFA. The findings point towards strong paracrine effects of APAs. Detected differences in subcutaneous fat might open new diagnostic strategies for hyperaldosteronism.