{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:43:30Z","timestamp":1791420210363,"version":"4.3.3"},"reference-count":60,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Union\u2013NextGenerationEU"},{"name":"Italian Ministry of University and Research","award":["PNRR-M4C2-I1.3"],"award-info":[{"award-number":["PNRR-M4C2-I1.3"]}]},{"name":"Italian Ministry of University and Research","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>It has been claimed that thyroid dysfunction contributes to the spectrum of Klinefelter syndrome (KS); however, studies are scarce.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>In a retrospective longitudinal study, we aimed at describing the hypothalamic-pituitary-thyroid (HPT) axis and thyroid ultrasonographic (US) appearance in patients with KS throughout the life span.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 254 patients with KS (25.9 \u00b1 16.1 years) were classified according to their pubertal and gonadal status and compared with different groups of non-KS age-matched individuals with normal thyroid function, treated and untreated hypogonadism, or chronic lymphocytic thyroiditis. We assessed serum thyroid hormone levels, antithyroid antibodies, US thyroid parameters, and in vitro pituitary type 2 deiodinase (D2) expression and activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thyroid autoimmunity was more prevalent among individuals with KS at all ages, although the antibody (Ab)-negative vs Ab-positive cohorts were not different. Signs of thyroid dysfunction (reduced volume, lower echogenicity, and increased inhomogeneity) were more prominent in KS than in euthyroid controls. Free thyroid hormones were lower in prepubertal, pubertal, and adult patients with KS, whereas thyrotropin values were lower only in adults. Peripheral sensitivity to thyroid hormones was unaltered in KS, suggesting a dysfunctional HPT axis. Testosterone (T) was the only factor associated with thyroid function and appearance. In vitro testing demonstrated an inhibitory effect of T on pituitary D2 expression and activity, supporting enhanced central sensing of circulating thyroid hormones in hypogonadism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>From infancy through adulthood, KS is characterized by increased morphofunctional abnormalities of the thyroid gland, combined with a central feedback dysregulation sustained by the effect of hypogonadism on D2 deiodinase.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad281","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T22:07:06Z","timestamp":1684793226000},"page":"e1329-e1340","source":"Crossref","is-referenced-by-count":16,"title":["Altered Thyroid Feedback Loop in Klinefelter Syndrome: From Infancy Through the Transition to Adulthood"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-4101","authenticated-orcid":false,"given":"Francesco","family":"Carlomagno","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome , Rome 00161 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-2809","authenticated-orcid":false,"given":"Marianna","family":"Minnetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome , Rome 00161 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Angelini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome , Rome 00161 , 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-8609","authenticated-orcid":false,"given":"Alessia","family":"Aureli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome , Rome 00161 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Anzuini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome , Rome 00161 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-1471","authenticated-orcid":false,"given":"Roberto","family":"Paparella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cSapienza\u201d University of Rome , Rome 00161 , 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