Sexual Pseudo-Precocity Caused by a Somatic Activating Mutation of the LH Receptor Preceding True Sexual Precocity

Abstract

Aim: We describe the clinical features of a 6-year-old boy with sexual precocity caused by a somatic activating mutation of the luteinizing hormone (LH) receptor gene preceding gonadotropin-releasing hormone (GnRH)-dependent sexual precocity. Study Design: Genomic DNA was extracted from the right testis and from the peripheral leukocytes followed by DNA amplification and sequencing of the LH receptor gene. We described the clinical characteristics including anthropometric parameters, bone age, and endocrine evaluation when the boy presented with sexual precocity. These data were compared with the clinical and hormonal evaluation after orchiectomy preceding GnRH-dependent sexual precocity and after subsequent treatment with GnRH agonist. Results: No mutation was found in the sequence of the LH receptor gene extracted from peripheral leukocytes. Interestingly, sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of Asp⁵⁷⁸His. Despite normalization of plasma testosterone, true precocious puberty was triggered within a year. Conclusions: Inmales with GnRH-independent sexual precocity the presence of small testicular Leydig cell tumorous lesions harboring a somatic mutation of the LH receptor gene should be considered. A close follow-up of affected patients should be instigated in order to monitor recurrence or subsequent true precocity.

Clinical and metabolic findings in a 6‐year‐old boy with a Leydig cell tumour

“…This phenomenon was also observed in four other patients with a Leydig cell tumour (9,11–13) and furthermore in children with congenital adrenal hyperplasia, familial male precocious puberty, McCune Albright syndrome and in other rare diseases. However, the true incidence in this condition is remains unclear because long‐term follow‐ups of children with Leydig cell tumours are not available.…”

True Precocious Puberty Following Treatment of a Leydig Cell Tumor: Two Case Reports and Literature Review

“…A similar prevalence of tumors between the right and left testes was observed and in all patients the histological analysis showed a Leydig cell tumor. ( 5 , 6 , 8 ).…”

“…Kiepe et al described a 6.6-year-old boy with sexual pseudo-precocity caused by a somatic activating mutation of the LH-receptor. One year after surgery, he developed a gonadotropin-dependent precocious puberty ( 6 ). Two other cases have been described in the literature, one in 2011 ( 7 ) and the other in 2012 ( 8 ).…”

Gonadotropin-Dependent Precocious Puberty in an 8-Year-Old Boy with Leydig Cell Testicular Tumor

“…In fact, when prepubertal children are exposed to testosterone, this can trigger the development of central precocious puberty, either from the priming effect of the sex steroid on the hypothalamus or from sudden lowering of sex steroid levels following improvement in the control of gonadotropin-independent precocious puberty [7,18,19]. There are few reported cases of central precocious puberty after treatment of testicular Leydig cell tumors [5,20,21,22,23]. …”