Endocrine Abstracts

Primary adrenal insufficiency is due to impairment of the adrenal gland with ~80% of the cases being due to autoimmune adrenalitis (Addison’s disease). Other cases of primary adrenal insufficiency might be idiopathic, caused by adrenal metastases, or due to congenital adrenal hyperplasia. Adrenal insufficiency might also be induced by infectious diseases e.g. COVID-19 and, as seen lately in an increasing number of patients, by novel medications targeting hypertension and cancer. Lastly, surgical bilateral adrenalectomy as required in certain adrenal tumors cause complete adrenal insufficiency. Currently, hormone replacement therapies are the main treatment option for adrenal insufficiencies, but are often coupled with significant side effects. Therefore, therapeutic alternatives are desirable for these patients. We have shown that transplantation of bovine adrenocortical cells is successful in animal models of adrenal insufficiency, and that the expression of progenitor markers is associated with the functionality. Thus, stem cell replacement therapy is an attractive alternative to current treatments. Stem cell-based therapies could involve either adult adrenal stem cells or stem cells derived through in vitro differentiation of pluripotent cells. Until now, limited in vivo studies have been performed using reprogrammed mouse or human cells in the adrenal field. Differentiation into steroidogenic cells has only been achieved by forced expression of NR5A1 (SF-1), the master regulator of steroidogenesis and differentiation of pituitary gonadotrophs, adrenal glands, and gonads. Although cells are viable after implantation into mice, full functionality and responsiveness to adrenal stimuli have not been reported. These observations might be due to incomplete differentiation and limited steroidogenic potential of the cells before transplantation. Thus, optimization is required. Looking forward, generation of bona-fide steroidogenic cells from humans combined with novel biomaterials and encapsulation in immune-isolating devices might offer alternative therapies for patients with adrenal insufficiency.