A rare cause of hypertestosteronemia in a 68-year-old patient: a Leydig cell tumor due to a somatic GNAS (guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1)-activating mutation.
Leydig cell tumors of the testis are the most common type of non-germ  cell testicular tumors. In adult patients, gynecomastia, oligozoospermia,  erectile dysfunction, and other signs of feminization can be present, whereas  testosterone levels are frequently in the normal range or slightly reduced. We  describe a patient with a history of impaired sexual function, as well as  progressive enlargement of the left testis, without gynecomastia. Hormonal  evaluation demonstrated very high testosterone, estrogen, and  pan-alpha-inhibin levels. Magnetic resonance imaging revealed the  presence of left testicular hypertrophy without evidence of testicular mass.  After left orchiectomy, histologic examination confirmed the diagnosis of  Leydig cell tumor, and steroid hormone levels normalized. A heterozygous  missense somatic gsp mutation (R201C) was found in tumoral tissue,  whereas no mutation was found in the surrounding normal tissue or in leukocyte  DNA. This case provides evidence that somatic activating gsp mutation  in Leydig cells may result in tumor development, leading to overexpression of  the inhibin alpha subunit and hyperactivity of the testosterone biosynthetic  pathway.
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Department of Endocrinology, Metabolism and Cancer, Institut Cochin, Paris, France.
Rossella
R
Libé
Amato
A
Fratticci
Najiba
N
Lahlou
François R
FR
Jornayvaz
Frédérique
F
Tissier
Estelle
E
Louiset
Jean
J
Guibourdenche
Annick
A
Vieillefond
Marc
M
Zerbib
Jérôme
J
Bertherat
D000368:Aged; D002864:Chromogranins; D004958:Estradiol / Q000097:blood; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000097:blood / Q000235:genetics*; D006801:Humans; D007265:Inhibins / Q000097:blood*; D007984:Leydig Cell Tumor / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D020125:Mutation, Missense; D009919:Orchiectomy; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013739:Testosterone / Q000097:blood*
D002864:Chromogranins; C094377:inhibin-alpha subunit; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs