title: Male LH-independent sexual precocity in a 3.5-year-old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor.
abstract: We describe the clinical features of severe sexual precocity in a 3.5-yr-old boy. Hormonal evaluation showed LH-independent T hypersecretion. Initial examination of the adrenals and testes revealed no evidence of congenital adrenal hyperplasia, hCG- or androgen-secreting tumors, or McCune-Albright syndrome. In the coding sequence of the LH receptor gene no activating mutation was found. Spironolactone (5.7 mg/kg x d) and testolactone (40 mg/kg x d) were unsuccessful in suppressing the elevated concentration of T. To further determine the origin of the elevated serum T, a selective venous sampling procedure was planned. However before the sampling procedure, high resolution ultrasound examination showed a small tumor in the left testis, which was removed. Histology proved the tumor to be a Leydig cell adenoma. Sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of aspartic acid at position 578 with histidine, which has been shown to be a constitutively activating mutation. These findings indicate that in male patients with gonadotropin-independent sexual precocity, the presence of small testicular Leydig cell tumors harboring a somatic mutation of the LH receptor gene should be considered.
authors.affiliation: Department of Hematology/Oncology and Endocrinology, University Children's Hospital, 45122 Essen, Germany. annette.richter-unruh@uni-essen.de
authors.forename: A
authors.initials: A
authors.lastname: Richter-Unruh
authors.forename: H T
authors.initials: HT
authors.lastname: Wessels
authors.forename: U
authors.initials: U
authors.lastname: Menken
authors.forename: M
authors.initials: M
authors.lastname: Bergmann
authors.forename: K
authors.initials: K
authors.lastname: Schmittmann-Ohters
authors.forename: J
authors.initials: J
authors.lastname: Schaper
authors.forename: S
authors.initials: S
authors.lastname: Tappeser
authors.forename: B P
authors.initials: BP
authors.lastname: Hauffa
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence / Q000235:genetics; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D016678:Genome; D006579:Heterozygote; D006801:Humans; D007984:Leydig Cell Tumor / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D007986:Luteinizing Hormone / Q000502:physiology*; D008297:Male; D009154:Mutation / Q000502:physiology*; D011629:Puberty, Precocious / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics*; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D014463:Ultrasonography
chemical_list: D011974:Receptors, LH; D007986:Luteinizing Hormone; D004247:DNA