{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T17:13:40Z","timestamp":1764609220949,"version":"3.46.0"},"reference-count":28,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"abstract":"<jats:p>Introduction: TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS\/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases. Case Presentation: Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol\/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS\/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A&gt;G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency. Conclusion: Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.<\/jats:p>","DOI":"10.1159\/000539796","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T17:15:29Z","timestamp":1721668529000},"page":"633-638","source":"Crossref","is-referenced-by-count":1,"title":["Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A&gt;G, p.(Thr58Ala) Mutation in the TBX19 Gene"],"prefix":"10.1159","volume":"98","author":[{"given":"Paul-Martin","family":"Holterhus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Roll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Gaida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Richter-Unruh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-6879","authenticated-orcid":false,"given":"Alexandra E.","family":"Kulle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kaschta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela F.","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan A.","family":"Wudy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4351-1834","authenticated-orcid":false,"given":"Thomas","family":"Reinehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"doi-asserted-by":"publisher","key":"ref1","DOI":"10.1101\/gad.1065703"},{"doi-asserted-by":"publisher","key":"ref2","DOI":"10.1016\/s0092-8674(01)00282-3"},{"doi-asserted-by":"publisher","key":"ref3","DOI":"10.1101\/gad.1065603"},{"doi-asserted-by":"publisher","key":"ref4","DOI":"10.1080\/07853890600994963"},{"doi-asserted-by":"publisher","key":"ref5","DOI":"10.1210\/jc.2011-1659"},{"doi-asserted-by":"publisher","key":"ref6","DOI":"10.1515\/jpem.2004.17.7.1017"},{"doi-asserted-by":"publisher","key":"ref7","DOI":"10.1530\/eje.0.1510463"},{"doi-asserted-by":"publisher","key":"ref8","DOI":"10.1210\/jc.2004-1300"},{"doi-asserted-by":"publisher","key":"ref9","DOI":"10.3389\/fendo.2022.1080649"},{"doi-asserted-by":"publisher","key":"ref10","DOI":"10.1016\/S0140-6736(21)00136-7"},{"doi-asserted-by":"publisher","key":"ref11","DOI":"10.1159\/000506740"},{"doi-asserted-by":"publisher","key":"ref12","DOI":"10.1530\/EDM-21-0128"},{"doi-asserted-by":"publisher","key":"ref13","DOI":"10.1007\/s42000-019-00096-7"},{"doi-asserted-by":"publisher","key":"ref14","DOI":"10.3389\/fped.2019.00546"},{"doi-asserted-by":"publisher","key":"ref15","DOI":"10.1007\/s12020-017-1415-1"},{"doi-asserted-by":"publisher","key":"ref16","DOI":"10.1210\/jc.2013-3375"},{"doi-asserted-by":"publisher","key":"ref17","DOI":"10.1016\/j.jsbmb.2015.10.013"},{"doi-asserted-by":"publisher","key":"ref18","DOI":"10.1530\/EJE-16-0953"},{"doi-asserted-by":"publisher","key":"ref19","DOI":"10.1159\/000488028"},{"doi-asserted-by":"publisher","key":"ref20","DOI":"10.1210\/jendso\/bvad155"},{"doi-asserted-by":"publisher","key":"ref21","DOI":"10.1530\/EC-23-0002"},{"doi-asserted-by":"publisher","key":"ref22","DOI":"10.1097\/00000433-199706000-00020"},{"doi-asserted-by":"publisher","key":"ref23","DOI":"10.2147\/TCRM.S238435"},{"doi-asserted-by":"publisher","key":"ref24","DOI":"10.1007\/s11154-022-09756-3"},{"doi-asserted-by":"publisher","key":"ref25","DOI":"10.1210\/jendso\/bvac058"},{"doi-asserted-by":"publisher","key":"ref26","DOI":"10.1111\/j.1365-2265.1995.tb02037.x"},{"doi-asserted-by":"publisher","key":"ref27","DOI":"10.1530\/EJE-14-1084"},{"doi-asserted-by":"publisher","key":"ref28","DOI":"10.1111\/cen.14445"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/hrp\/article-pdf\/doi\/10.1159\/000539796\/4265306\/000539796.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000539796","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T17:09:58Z","timestamp":1764608998000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000539796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,12,1]]},"published-print":{"date-parts":[[2025,12,3]]}},"URL":"https:\/\/doi.org\/10.1159\/000539796","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"type":"print","value":"1663-2818"},{"type":"electronic","value":"1663-2826"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}