Endocrine Abstracts

Diseases and cancers of the adrenal gland disrupt key processes in the body such as stress and immune responses, sexual maturation, and salt balance and therefore have serious, potentially fatal consequences. Adrenocortical tumours include adrenocortical adenomas (ACAs) and adrenocortical carcinomas (ACCs). While ACAs are typically benign and often managed effectively, ACCs present significant clinical challenges due to limited treatment options and poor prognoses. The inherent rarity of these tumours makes development of novel therapies even more challenging. Development of new physiologically relevant in vitro models are critical in improving understanding of adrenocortical tumours and advancing therapeutic development. Here 3D organoid-like structures have been generated from patient-derived adrenocortical tumour tissue with a range of different pathologies and adjacent ‘normal’ adrenal tissue. Patient cells were seeded in suspension culture and allowed to grow for 2-3 weeks to generate organoids. Organoids were collected for embedding, sectioning, and immunohistochemistry staining for various antigens marking region specific adrenal populations. This histological analysis confirmed that patient-derived organoids retained not only the main cytoarchitecture but also key antigenic compositions characteristic of their tumours of origin, including expression of steroidogenic enzymes. Steroid analysis was also carried out on the organoid medium using ELISA and mass spectrometry to compare the steroid output of the organoids to the clinical analysis of patient serum, confirming that organoids were functional and steroidogenic. These findings support the potential of adrenal organoids as promising in vitro models that preserve the key histological and molecular characteristics of their tissues of origin. Further validation is required to optimise and fully establish their translational and research applications.