{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:32:20Z","timestamp":1792801940265,"version":"4.5.0"},"reference-count":180,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"University of Sydney Postgraduate Award","id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Royal Adelaide Hospital Research Committee Dawes Scholarship","id":[{"id":"https:\/\/ror.org\/00carf720","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Adrenal Research","award":["DFG CRC\/TRR 205)"],"award-info":[{"award-number":["DFG CRC\/TRR 205)"]}]},{"name":"Transcampus International Research Training Group","award":["2251"],"award-info":[{"award-number":["2251"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists. Adrenocortical cell therapy and gene therapy may obviate many of the shortcomings of adrenal hormone replacement. Physiological cortisol secretion regulated by pituitary adrenocorticotropin could be achieved through allogeneic adrenocortical cell transplantation, production of adrenal-like steroidogenic cells from either stem cells or lineage conversion of differentiated cells, or for CAH, gene therapy to replace or repair a defective gene. The adrenal cortex is a high-turnover organ and thus failure to incorporate progenitor cells within a transplant will ultimately result in graft exhaustion. Identification of adrenocortical progenitor cells is equally important in gene therapy, for which new genetic material must be specifically integrated into the genome of progenitors to ensure a durable effect. Delivery of gene-editing machinery and a donor template, allowing targeted correction of the 21-hydroxylase gene, has the potential to achieve this. This review describes advances in adrenal cell transplants and gene therapy that may allow physiological cortisol production for children and adults with PAI.<\/jats:p>","DOI":"10.1210\/clinem\/dgac751","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T23:44:52Z","timestamp":1673135092000},"page":"1273-1289","source":"Crossref","is-referenced-by-count":21,"title":["Future Directions for Adrenal Insufficiency: Cellular Transplantation and Genetic Therapies"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-220X","authenticated-orcid":false,"given":"Lara E","family":"Graves","sequence":"first","affiliation":[{"name":"Institute of Endocrinology and Diabetes, Children's Hospital at Westmead , Westmead, New South Wales 2145 , Australia"},{"name":"Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network , Westmead, New South Wales 2145 , Australia"},{"name":"Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Westmead, New South Wales 2145 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-0981","authenticated-orcid":false,"given":"David J","family":"Torpy","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital , 5000 Adelaide, South Australia , Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide , Adelaide, South Australia 5005 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Toby","family":"Coates","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide , Adelaide, South Australia 5005 , Australia"},{"name":"Central Northern Adelaide Renal 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