{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:47Z","timestamp":1784527427344,"version":"3.55.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"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. Med."],"abstract":"<jats:p>\n                    Gordon syndrome (Pseudohypoaldosteronism type II) is a rare autosomal dominant disorder characterized by hyperkalemia, hypertension, and metabolic acidosis. Among the four causative genes,\n                    <jats:italic>CUL3<\/jats:italic>\n                    mutations produce the most severe phenotype, yet endocrine manifestations beyond growth delay remain poorly described. We report a 22-year-old male who presented with chronic hyperkalemia, hypertension, insulin resistance with steatohepatitis, and testicular hypoplasia with elevated gonadotropins, consistent with compensated primary testicular dysfunction. Genetic analysis identified a\n                    <jats:italic>de novo<\/jats:italic>\n                    heterozygous\n                    <jats:italic>CUL3<\/jats:italic>\n                    c.1207-26A&amp;gt;G splice-site mutation resulting in exon 9 skipping. Treatment with hydrochlorothiazide normalized blood pressure and serum potassium while improving metabolic and hormonal abnormalities. Notably, these improvements reversed upon treatment discontinuation. This case suggests that certain endocrine manifestations in\n                    <jats:italic>CUL3<\/jats:italic>\n                    -related Gordon syndrome may be secondary to chronic electrolyte imbalance rather than direct genetic effects, highlighting the importance of comprehensive endocrine evaluation and sustained thiazide therapy in affected patients.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1862901","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:48Z","timestamp":1784525748000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Atypical endocrine manifestations in Gordon syndrome caused by CUL3 mutation: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Mahsa","family":"Fatahichegeni","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Amin","family":"Ansarian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3390\/genes10120986","article-title":"The molecular genetics of Gordon syndrome","volume":"10","author":"Mabillard","year":"2019","journal-title":"Genes."},{"key":"B2","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1161\/HYPERTENSIONAHA.113.02187","article-title":"Pseudohypoaldosteronism type II: history, arguments, answers, and still some questions","volume":"63","author":"Healy","year":"2014","journal-title":"Hypertension."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e84341","DOI":"10.7759\/cureus.84341","article-title":"Revelation of Gordon syndrome: a case of persistent hyperkalemia","volume":"17","author":"Modi","year":"2025","journal-title":"Cureus."},{"key":"B4","doi-asserted-by":"publisher","first-page":"F1513","DOI":"10.1152\/ajprenal.00440.2013","article-title":"A molecular update on pseudohypoaldosteronism type II","volume":"305","author":"Pathare","year":"2013","journal-title":"Am J Physiol Ren Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s12964-023-01269-z","article-title":"Insights into the diverse mechanisms and effects of variant CUL3-induced familial hyperkalemic hypertension","volume":"21","author":"Sharma","year":"2023","journal-title":"Cell Communication and Signaling."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1161\/HYPERTENSIONAHA.124.23385","article-title":"Update on low-renin hypertension: current understanding and future direction","volume":"81","author":"Shah","year":"2024","journal-title":"Hypertension."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3248","DOI":"10.1210\/jcem.87.7.8449","article-title":"Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density","volume":"87","author":"Mayan","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1016\/j.ekir.2021.07.025","article-title":"The variety of genetic defects explains the phenotypic heterogeneity of Familial Hyperkalemic Hypertension","volume":"6","author":"Hureaux","year":"2021","journal-title":"Kidney International Reports."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e2320934121","DOI":"10.1073\/pnas.2320934121","article-title":"Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance","volume":"121","author":"Gu","year":"2024","journal-title":"Proc Nat Acad Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physrev.00008.2017","article-title":"Pancreatic \u03b2-cell electrical activity and insulin secretion: of mice and men","volume":"98","author":"Rorsman","year":"2018","journal-title":"Physiol Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3390\/ijms20010126","article-title":"The effects of systemic and local acidosis on insulin resistance and signaling","volume":"20","author":"Baldini","year":"2018","journal-title":"Int J Mol Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1161\/01.ATV.0000122852.22604.78","article-title":"Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited","volume":"24","author":"Ceriello","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1210\/jc.2004-2190","article-title":"Increasing insulin resistance is associated with a decrease in leydig cell testosterone secretion in men","volume":"90","author":"Pitteloud","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1590\/S0004-27302009000800015","article-title":"Motta LD, Casulari LA. Relationship between insulin and hypogonadism in men with metabolic syndrome","volume":"53","author":"Caldas","year":"2009","journal-title":"Arq Bras Endocrinol Metabol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1095\/biolreprod.105.045484","article-title":"Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis","volume":"74","author":"Wang","year":"2006","journal-title":"Biol Reprod."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1862901\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:49Z","timestamp":1784525749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1862901\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":15,"alternative-id":["10.3389\/fmed.2026.1862901"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1862901","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1862901"}}