{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:19:47Z","timestamp":1787980787049,"version":"build-2784847793"},"reference-count":18,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0617_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Familial nonautoimmune hyperthyroidism (FNAH) is a rare disorder caused by activating germline variants in the thyroid-stimulating hormone receptor gene (\n                      <jats:italic>TSHR<\/jats:italic>\n                      ) and can mimic antibody-negative Graves\u2019 disease. We report a family with hyperthyroidism and the TSHR variant Gly413Ser and provide clinical, segregation, and functional evidence that this p10-region variant is a novel cause of FNAH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0617_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>The disorder was recognized after a 15-year-old boy presented with abdominal pain and diarrhea and was found to have suppressed thyrotropin, high-normal free thyroxine, and slightly elevated free triiodothyronine, without thyrotropin receptor antibodies (TRAb) or ophthalmopathy. Family review revealed multigenerational TRAb-negative hyperthyroidism. Genetic testing identified NM_000369.5(TSHR):c.1237G&gt;A, p.(Gly413Ser), initially classified as a variant of uncertain significance. Twelve family members were investigated: nine affected individuals carried the variant, and three unaffected relatives tested negative. Age at diagnosis ranged from 10 to 73\u202fyears. Antithyroid drugs gave symptom relief, but relapse occurred after withdrawal; definitive (ablative) treatment was performed in all but one of the affected family members. Basal cyclic adenosine monophosphate (cAMP) production by the Gly413Ser variant was approximately threefold increased, with unchanged inositol 1-phosphate and thyrotropin-stimulated responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0617_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TSHR Gly413Ser is a pathogenic activating variant causing FNAH. Persistent TRAb-negative hyperthyroidism, especially with familial clustering, should prompt TSHR genetic testing and cascade evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0617","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:56:21Z","timestamp":1787979381000},"source":"Crossref","is-referenced-by-count":0,"title":["TSHR Gly413Ser in familial nonautoimmune hyperthyroidism: a case report"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7926-3603","authenticated-orcid":false,"given":"Oskar","family":"Kelp","sequence":"first","affiliation":[{"name":"Hormone Laboratory, Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway"},{"name":"Biochemical Endocrinology and Metabolism Research Group , Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jostein","family":"F\u00f8rsvoll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Stavanger University Hospital , Stavanger , Norway"},{"name":"Department of Clinical Science , University of Bergen , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Bischof","sequence":"additional","affiliation":[{"name":"Medical Faculty , Rudolf Sch\u00f6nheimer Institute of Biochemistry, Leipzig University , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"St\u00e4ubert","sequence":"additional","affiliation":[{"name":"Medical Faculty , Rudolf Sch\u00f6nheimer Institute of Biochemistry, Leipzig University , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Sch\u00f6neberg","sequence":"additional","affiliation":[{"name":"Medical Faculty , Rudolf Sch\u00f6nheimer Institute of Biochemistry, Leipzig University , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne Gro","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asgeir","family":"Lande","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri","family":"Carlsen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Stavanger University Hospital , Stavanger , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Medb\u00f8e","family":"Thorsby","sequence":"additional","affiliation":[{"name":"Hormone Laboratory, Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway"},{"name":"Biochemical Endocrinology and Metabolism Research Group , Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Bauer","family":"Westbye","sequence":"additional","affiliation":[{"name":"Hormone Laboratory, Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway"},{"name":"Biochemical Endocrinology and Metabolism Research Group , Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May K. 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