{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:47:58Z","timestamp":1764604078478,"version":"3.37.3"},"reference-count":22,"publisher":"Endocrinology Research Centre","issue":"3","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p><jats:bold>BACKGROUND:<jats:italic>\u00a0<\/jats:italic><\/jats:bold>X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70\u201380% of patients, adrenal insufficiency (AI) is a\u00a0life-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms.<\/jats:p><jats:p><jats:bold>AIM:<jats:italic>\u00a0<\/jats:italic><\/jats:bold>To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.<\/jats:p><jats:p><jats:bold>MATERIALS AND METHODS:<jats:italic>\u00a0<\/jats:italic><\/jats:bold>A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children\u2019s Clinical Hospital (Moscow, Russia) for 2014\u20132022. All of patients were diagnosed\u00a0with primary AI and a genetically confirmed X-ALD.<\/jats:p><jats:p><jats:bold>RESULTS:<jats:italic>\u00a0<\/jats:italic><\/jats:bold>The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years at\u00a0the preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15\/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10\/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) the\u00a0cerebral form of the disease (cALD) was established, in 16.6% \u2014 adrenomyeloneuropathy (AMN), and in 24.2% \u2014 isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11\u00a0and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI.<\/jats:p><jats:p><jats:bold>CONCLUSION:<jats:italic>\u00a0<\/jats:italic><\/jats:bold>It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed to\u00a0prescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.<\/jats:p>","DOI":"10.14341\/probl13335","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T15:09:14Z","timestamp":1721056154000},"page":"83-92","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":3,"title":["Adrenal insufficiency as part of X-linked adrenoleukodystrophy"],"prefix":"10.14341","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-641X","authenticated-orcid":true,"given":"S. R.","family":"Enikeeva","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4915-1267","authenticated-orcid":true,"given":"I. S.","family":"Chugunov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-6561","authenticated-orcid":true,"given":"M. A.","family":"Kareva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-6105","authenticated-orcid":true,"given":"M. V.","family":"Kurkina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-6561","authenticated-orcid":true,"given":"E. Y.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0192-8356","authenticated-orcid":true,"given":"S. V.","family":"Michailova","sequence":"additional","affiliation":[{"name":"Pirogov Russian National Research Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-5732","authenticated-orcid":true,"given":"O. B.","family":"Bezlepkina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-4627","authenticated-orcid":true,"given":"V. A.","family":"Peterkova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-9742","authenticated-orcid":true,"given":"N. G.","family":"Mokrysheva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2023,12,5]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Engelen M, van Ballegoij WJC, Mallack EJ, et al. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy. Neurology. 2022;99(21):940-951. doi: https:\/\/doi.org\/10.1212\/WNL.0000000000201374","key":"ref1","DOI":"10.1212\/WNL.0000000000201374"},{"doi-asserted-by":"crossref","unstructured":"Turk BR, Theda C, Fatemi A, Moser AB. X\u2010linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies. Int J Dev Neurosci. 2020;80(1):52-72. doi: https:\/\/doi.org\/10.1002\/jdn.10003","key":"ref2","DOI":"10.1002\/jdn.10003"},{"unstructured":"Lomonosova E.Z., Rudenskaya G.E., Shekhter O.V., i dr. Kliniko-genealogicheskie, biokhimicheskie i molekulyarno-geneticheskie kharakteristiki Kh-stseplennoi adrenoleikodistrofii \/\/ Meditsinskaya genetika. \u2014 2006. \u2014 T. 5. \u2014 \u21166 (48). \u2014 S. 38\u201347","key":"ref3"},{"unstructured":"Mikhailova S.V. Differentsial'naya diagnostika nasledstvennykh neirometabolicheskikh zabolevanii u detei \/\/ Rossiiskii gosudarstvennyi meditsinskii universitet. \u2014 2010","key":"ref4"},{"unstructured":"Orlova E.M. Federal'nye klinicheskie rekomendatsii po vedeniyu detei i podrostkov s pervichnoi khronicheskoi nadpochechnikovoi nedostatochnost'yu \/\/ Problemy endokrinologii. \u2014 2013. \u2014 T. 59. \u2014 \u21166. \u2014 S. 44\u20139","key":"ref5"},{"unstructured":"Orlova E.M., Kareva M.A. Pervichnaya nadpochechnikovaya nedostatochnost' u detei: klinicheskie varianty, diagnostika, lechenie \/\/ Posobie dlya vrachei.\u2014 2008: 51 s.","key":"ref6"},{"doi-asserted-by":"crossref","unstructured":"Voinova V.Yu., Shkol'nikova M.A., Nikolaeva E.A. Vozmozhnosti novykh tekhnologii genomnogo redaktirovaniya v lechenii Kh-stseplennoi adrenoleikodistrofii \/\/ Rossiiskii vestnik perinatologii i pediatrii. \u2014 2020. \u2014 T. 65. \u2014 \u21162. \u2014 S. 104\u20137. doi: https:\/\/doi.org\/10.21508\/1027-4065-2020-65-2-104-107","key":"ref7","DOI":"10.21508\/1027-4065-2020-65-2-104-107"},{"unstructured":"Klement'eva N.V., Popov V.S., Isaev A.A., Kiselev S.L. Poluchenie uluchshennogo varianta vektora dlya gennoi terapii Kh-stseplennoi adrenoleikodistrofii \/\/ Geny i Kletki. \u2014 2019. \u2014 T. 14. \u2014 \u21163. \u2014 C. 112-112. doi: https:\/\/doi.org\/\/10.23868\/gc122838","key":"ref8"},{"unstructured":"Novikov P.V., Mikhailova S.V., Zakharova E.Yu., Voinova V.Yu. Federal'nye klinicheskie rekomendatsii po diagnostike i lecheniyu Kh-stseplennoi adrenoleikodistrofii. Mai 2013 g. Dostupno na: https:\/\/med-gen.ru\/docs\/adrenoleikodistrofiya.pdf?ysclid=lbvzlttbw113179144","key":"ref9"},{"doi-asserted-by":"crossref","unstructured":"Capalbo D, Moracas C, Cappa M, et al. Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort. J Clin Endocrinol Metab. 2021;106(3):762-773. doi: https:\/\/doi.org\/10.1210\/clinem\/dgaa881","key":"ref10","DOI":"10.1210\/clinem\/dgaa881"},{"doi-asserted-by":"crossref","unstructured":"Moser AB, Seeger E, Raymond G V. Newborn Screening for X-Linked Adrenoleukodystrophy: Past, Present, and Future. Int J Neonatal Screen. 2022;8(1):16. doi: https:\/\/doi.org\/10.3390\/ijns8010016","key":"ref11","DOI":"10.3390\/ijns8010016"},{"doi-asserted-by":"crossref","unstructured":"Lee S, Clinard K, Young SP, et al. Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina. JAMA Netw Open. 2020;3(1):e1920356. doi: https:\/\/doi.org\/10.1001\/jamanetworkopen.2019.20356","key":"ref12","DOI":"10.1001\/jamanetworkopen.2019.20356"},{"doi-asserted-by":"crossref","unstructured":"Schiller S, Henneke M, G\u00e4rtner J. Opening New Horizons in the Treatment of Childhood Onset Leukodystrophies. Neuropediatrics. 2019;50(04):211-218. doi: https:\/\/doi.org\/10.1055\/s-0039-1685529","key":"ref13","DOI":"10.1055\/s-0039-1685529"},{"doi-asserted-by":"crossref","unstructured":"Eichler F, Duncan C, Musolino PL, et al. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2017. doi: https:\/\/doi.org\/10.1056\/nejmoa1700554","key":"ref14","DOI":"10.1056\/NEJMoa1700554"},{"doi-asserted-by":"crossref","unstructured":"Burtman E, Regelmann MO. Endocrine Dysfunction in X-Linked Adrenoleukodystrophy. Endocrinol Metab Clin North Am. 2016;45(2):295-309. doi: https:\/\/doi.org\/10.1016\/j.ecl.2016.01.003","key":"ref15","DOI":"10.1016\/j.ecl.2016.01.003"},{"doi-asserted-by":"crossref","unstructured":"Huffnagel IC, Laheji FK, Aziz-Bose R, et al. The Natural History of Adrenal Insufficiency in X-Linked Adrenoleukodystrophy: An International Collaboration. J Clin Endocrinol Metab. 2019;104(1):118-126. doi: https:\/\/doi.org\/10.1210\/jc.2018-01307","key":"ref16","DOI":"10.1210\/jc.2018-01307"},{"doi-asserted-by":"crossref","unstructured":"Dubey P, Raymond G V., Moser AB, Kharkar S, Bezman L, Moser HW. Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr. 2005. doi: https:\/\/doi.org\/10.1016\/j.jpeds.2004.10.067","key":"ref17","DOI":"10.1016\/j.jpeds.2004.10.067"},{"doi-asserted-by":"crossref","unstructured":"Ryalls MR, Gan H-W, Davison JE. Adrenoleukodystrophy in the Differential Diagnosis of Boys Presenting with Primary Adrenal Insufficiency without Adrenal Antibodies. J Clin Res Pediatr Endocrinol. 2021;13(2):212-217. doi: https:\/\/doi.org\/10.4274\/jcrpe.galenos.2020.2020.0214","key":"ref18","DOI":"10.4274\/jcrpe.galenos.2020.2020.0214"},{"doi-asserted-by":"crossref","unstructured":"Polgreen LE, Chahla S, Miller W, et al. Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison\u2019s disease improves survival and neurological outcomes. Eur J Pediatr. 2011;170(8):1049-1054. doi: https:\/\/doi.org\/10.1007\/s00431-011-1401-1","key":"ref19","DOI":"10.1007\/s00431-011-1401-1"},{"doi-asserted-by":"crossref","unstructured":"Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi: https:\/\/doi.org\/10.1210\/jc.2015-1710","key":"ref20","DOI":"10.1210\/jc.2015-1710"},{"doi-asserted-by":"crossref","unstructured":"Huffnagel IC, van de Beek M-C, Showers AL, et al. Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy. Mol Genet Metab. 2017;122(4):209-215. doi: https:\/\/doi.org\/10.1016\/j.ymgme.2017.10.012","key":"ref21","DOI":"10.1016\/j.ymgme.2017.10.012"},{"doi-asserted-by":"crossref","unstructured":"Eyal O, Levin Y, Oren A, et al. Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors. Eur J Pediatr. 2019;178(5):731-738. doi: https:\/\/doi.org\/10.1007\/s00431-019-03348-1","key":"ref22","DOI":"10.1007\/s00431-019-03348-1"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13335\/10681","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T10:09:45Z","timestamp":1721124585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,5]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,7,14]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13335","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"type":"electronic","value":"2308-1430"},{"type":"print","value":"0375-9660"}],"subject":[],"published":{"date-parts":[[2023,12,5]]}}}