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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

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.
Journal of Andrology (Impact Factor: 1.69). 10/2011; 33(4):578-84. DOI: 10.2164/jandrol.111.013441
Source: PubMed

ABSTRACT 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.

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