{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T01:30:43Z","timestamp":1775698243149,"version":"3.50.1"},"reference-count":43,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD093622"],"award-info":[{"award-number":["R01HD093622"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01\u00a0HD083493"],"award-info":[{"award-number":["U01\u00a0HD083493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Autosomal dominant and rarely de novo gain-of-function variants in the LHCGR gene are associated with precocious male puberty, while somatic LHCGR variants have been found in isolated Leydig cell adenomas and Leydig cell hyperplasia. Bilateral diffuse Leydig cell tumor formation in peripheral precocious male puberty has not been reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>We present a boy with gonadotropin-independent precocious puberty and rapid virilization beginning in infancy resistant to standard therapy. Treatment with abiraterone in addition to letrozole and bicalutamide proved effective. Bilateral diffuse Leydig cell tumors were identified at age 5 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Whole-genome sequencing of tumor and blood samples was performed. The patient was confirmed to have bilateral, diffuse Leydig cell tumors harboring the somatic, gain-of-function p.Asp578His variant in the LHCGR gene. Digital droplet polymerase chain reaction of the LHCGR variant performed in tumor and blood samples detected low levels of this same variant in the blood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We report a young boy with severe gonadotropin-independent precocious puberty beginning in infancy who developed bilateral diffuse Leydig cell tumors at age 5 years due to a somatic gain-of-function p.Asp578His variant in LHCGR. The gain-of-function nature of the LHCGR variant and the developmental timing of the somatic mutation likely play a role in the risk of tumor formation. Abiraterone (a CYP17A1 inhibitor), in combination with an antiandrogen, aromatase inhibitor, and glucocorticoid, appears to be an effective therapy for severe peripheral precocious puberty in boys.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvac127","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T22:37:36Z","timestamp":1660343856000},"source":"Crossref","is-referenced-by-count":10,"title":["Precocious Puberty in a Boy With Bilateral Leydig Cell Tumors due to a Somatic Gain-of-Function <i>LHCGR<\/i> Variant"],"prefix":"10.1210","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-3218","authenticated-orcid":false,"given":"Chelsi","family":"Flippo","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health , Bethesda, Maryland 20892 , USA"},{"name":"Division of Endocrinology, Children\u2019s National Hospital , 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