{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:59Z","timestamp":1787026379917,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder caused by a congenital defect in the ATP-binding cassette transporters sub-family D member 1 gene (ABCD1) producing adrenoleukodystrophy protein (ALDP). According to population studies, X-ALD has an estimated birth prevalence of 1 in 17.000 subjects (considering both hemizygous males and heterozygous females), and there is no evidence that this prevalence varies among regions or ethnic groups. ALDP deficiency results in a defective peroxisomal \u03b2-oxidation of very long chain fatty acids (VLCFA). As a consequence of this metabolic abnormality, VLCFAs accumulate in nervous system (brain white matter and spinal cord), testis and adrenal cortex. All X-ALD affected patients carry a mutation on the ABCD1 gene. Nevertheless, patients with a defect on the ABCD1 gene can have a dramatic difference in the clinical presentation of the disease. In fact, X-ALD can vary from the most severe cerebral paediatric form (CerALD), to adult adrenomyeloneuropathy (AMN), Addison-only and asymptomatic forms. Primary adrenal insufficiency (PAI) is one of the main features of X-ALD, with a prevalence of 70% in ALD\/AMN patients and 5% in female carriers. The pathogenesis of X-ALD related PAI is still unclear, even if a few published data suggests a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of adrenal cell membrane function and ACTH receptor activity. The reason why PAI develops only in a proportion of ALD\/AMN patients remains incompletely understood. A growing consensus supports VLCFA assessment in all male children presenting with PAI, as early diagnosis and start of therapy may be essential for X-ALD patients. Children and adults with PAI require individualized glucocorticoid replacement therapy, while mineralocorticoid therapy is needed only in a few cases after consideration of hormonal and electrolytes status. Novel approaches, such as prolonged release glucocorticoids, offer potential benefit in optimizing hormonal replacement for X-ALD-related PAI. Although the association between PAI and X-ALD has been observed in clinical practice, the underlying mechanisms remain poorly understood. This paper aims to explore the multifaceted relationship between PAI and X-ALD, shedding light on shared pathophysiology, clinical manifestations, and potential therapeutic interventions.<\/jats:p>","DOI":"10.3389\/fendo.2023.1309053","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T07:06:05Z","timestamp":1700118365000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["X-linked adrenoleukodystrophy and primary adrenal insufficiency"],"prefix":"10.3389","volume":"14","author":[{"given":"Marco","family":"Cappa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Todisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Bizzarri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"B1","unstructured":"X-linked adrenoleucoystrophy2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4158\/EP15754.OR","article-title":"Increasing prevalence of Addison disease: results from a nationwide study","volume":"22","author":"Olafsson","year":"2016","journal-title":"Endocr Practice"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91829-w","article-title":"21-Hydroxylase, a major autoantigen in idiopathic Addison\u2019s disease","volume":"339","author":"Winqvist","year":"1992","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2522","article-title":"Clinical and immunological characteristics of autoimmune addison disease: A nationwide swedish multicenter study","volume":"102","author":"Dalin","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1210\/jcem.81.2.8636252","article-title":"X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison\u2019s disease in young adult male patients","volume":"81","author":"Laureti","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1111\/j.1440-1754.2004.00482.x","article-title":"Primaryadrenal insufficiency in childhood and adolescence: advances Indiagnosis and management","volume":"40","author":"Simm","year":"2004","journal-title":"J Paedia Children Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12159","article-title":"Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease","volume":"79","author":"Horn","year":"2013","journal-title":"Clin Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa881","article-title":"Primary adrenal insufficiency in childhood: data from a large nationwide cohort","volume":"106","author":"Capalbo","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","first-page":"81","article-title":"Hormonal evaluation in adrenoleukodystrophy","volume-title":"Adrenoleukodystrophy and Other Peroxisomal Disorders. 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