Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed Gonadotropins in a Patient With Testotoxicosis
| Autor: | Anders Juul, Hanne Frederiksen, Martin Blomberg Jensen, Ewa Rajpert-De Meyts, Anne Jørgensen, Niels E. Skakkebæk, Birgitte Grønkær Toft, Li Juel Mortensen, John E. Nielsen, Ann-Margrethe Rønholt, Anand C Loya, Peter Christiansen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Puberty Precocious Biology Biochemistry Bone and Bones Andrology 03 medical and health sciences Hormone Antagonists 0302 clinical medicine Endocrinology Internal medicine Testis medicine Humans Precocious puberty Spermatogenesis Testosterone 030219 obstetrics & reproductive medicine Biochemistry (medical) luteinizing hormone/choriogonadotropin receptor Intratubular germ cell neoplasia Bone age Neoplasms Germ Cell and Embryonal Receptors LH medicine.disease Body Height Fertility Ketoconazole 030220 oncology & carcinogenesis Body Composition Luteinizing hormone Gonadotropins Leydig Cell Tumor Hormone |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 102:4411-4416 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2017-01761 |
| Popis: | Context 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. Case Description 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-Müllerian 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. Conclusion 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|