{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:06:48Z","timestamp":1778033208106,"version":"3.51.4"},"reference-count":12,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n Testotoxicosis is an autosomal-dominant, male-limited disorder. Activating mutations in the luteinizing hormone receptor gene (LHCGR) cause high autonomous testosterone secretion, resulting in early-onset peripheral precocious puberty. Little is known about long-term consequences of testotoxicosis.<\/jats:p>\n <\/jats:sec>\n \n Case Description<\/jats:title>\n We present a rare case of a patient followed for 25 years with two remarkable outcomes: preserved fertility and germ cell neoplasia in situ (GCNIS). He presented with precocious puberty at 10 months of age and was diagnosed with testotoxicosis due to a de novo heterozygous Asp578Tyr mutation in LHCGR. Testicular biopsy in childhood showed Leydig cell hyperplasia with altered cell maturation. From infancy throughout adulthood, elevated testosterone and estradiol, low inhibin B and anti-M\u00fcllerian hormone, and completely suppressed follicle-stimulating hormone and luteinizing hormone were noted. Height acceleration and advanced bone age resulted in a reduced final height. Semen analysis revealed ongoing spermatogenesis, and the patient fathered a child by natural conception. Ketoconazole treatment decreased circulating testosterone in childhood, supported by experimental suppression of testosterone production in his adult testis tissue cultured ex vivo. At 25 years of age, ultrasound revealed a testicular tumor, identified as a Leydig cell adenoma, but unexpectedly with GCNIS present in adjacent seminiferous tubules.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The case illustrates that absence of gonadotropins but high intratesticular testosterone concentration is sufficient for spermatogenesis and to allow fatherhood. Our study is also the first description, to our knowledge, of GCNIS in a patient with testotoxicosis. We recommend regular clinical examination and ultrasonic evaluation of the testes in these patients due to potential increased risk of malignancy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2017-01761","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T18:09:08Z","timestamp":1507226948000},"page":"4411-4416","source":"Crossref","is-referenced-by-count":10,"title":["Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed Gonadotropins in a Patient With Testotoxicosis"],"prefix":"10.1210","volume":"102","author":[{"given":"Li","family":"Juel Mortensen","sequence":"first","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"Division of Bone and Mineral Research, Harvard School of Dental Medicine, Harvard University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Blomberg Jensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"Division of Bone and Mineral Research, Harvard School of Dental Medicine, Harvard University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Margrethe","family":"R\u00f8nholt","sequence":"additional","affiliation":[{"name":"Pediatric Department, Regionshospitalet Viborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand C","family":"Loya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte","family":"Gr\u00f8nk\u00e6r Toft","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels E","family":"Skakkeb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Rajpert-De Meyts","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, 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