{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:27:29Z","timestamp":1793608049591,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Variants in LHX3, encoding a LIM\u2010homeodomain transcription factor essential for pituitary and neuronal development, are a rare cause of combined pituitary hormone deficiency (CPHD). Affected patients typically exhibit deficiencies of growth hormone (GH), thyrotropin (TSH), prolactin (PRL), and gonadotropins, often accompanied by cervical spine rigidity or sensorineural hearing loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Description<\/jats:title>\n                    <jats:p>A 4.8\u2010year\u2010old boy presented with short stature and central hypothyroidism. Combined deficiencies of GH, TSH, and PRL were documented, while ACTH secretion remained intact. Cranial magnetic resonance imaging showed normal pituitary morphology. Neck mobility and audiological evaluation were unremarkable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evaluation<\/jats:title>\n                    <jats:p>A targeted next\u2010generation sequencing panel for panhypopituitarism was non\u2010diagnostic. Whole\u2010exome sequencing (WES) was performed at 10.5 years of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES identified a novel homozygous\n                      <jats:italic>LHX3<\/jats:italic>\n                      c.575\u2009G\u2009&gt;\u2009A, p.(Arg192His) variant located within the homeodomain. Segregation analysis confirmed parental heterozygosity. A younger sister carrying the same homozygous variant exhibited a similar endocrine phenotype. Growth velocity normalized on recombinant human GH replacement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case expands the phenotypic spectrum of\n                      <jats:italic>LHX3<\/jats:italic>\n                      \u2010related CPHD by demonstrating that a homeodomain missense variant may produce isolated endocrine deficiencies without structural, auditory, or motor abnormalities, and underscores the value of serial genetic re\u2010evaluation in unexplained CPHD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70198","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:45:30Z","timestamp":1785941130000},"page":"643-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Approach to The Patient With Combined Pituitary Hormone Deficiency Due to a Novel Homozygous LHX3 Variant"],"prefix":"10.1111","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7397-3071","authenticated-orcid":false,"given":"Sirmen K\u0131z\u0131lcan","family":"\u00c7etin","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4407-8953","authenticated-orcid":false,"given":"\u0130brahim","family":"Dikmen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-5781","authenticated-orcid":false,"given":"Elif","family":"\u00d6zsu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehra","family":"Aycan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3102-0242","authenticated-orcid":false,"given":"Merih","family":"Berbero\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0921-2694","authenticated-orcid":false,"given":"Zeynep","family":"\u015e\u0131klar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara University School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.10.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335929"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600994963"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2006.12.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/76041"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(94)90034-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5264.1004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81704-3"},{"issue":"8","key":"e_1_2_10_11_1","first-page":"2701","article-title":"Molecular Analysis of LHX3 and PROP\u20101 in Pituitary Hormone Deficiency Patients With Posterior Pituitary Ectopia","volume":"85","author":"Sloop K. 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