Venous sampling can be crucial in identifying the testicular origin of idiopathic male luteinising hormone-independent sexual precocity

Abstract

the somatic activating mutation (Asp578His) of the luteinising hormone receptor gene is not only present in Leydig cell adenomas, but can also be found in nodular Leydig cell hyperplasia. Venous sampling can play a vital role in determining the origin of elevated testosterone levels.

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

“…Recently, Liu et al [9] described 3 boys, Canto et al [22] described 2 boys and Richter-Unruh et al [23] described 1 boy with Leydig cell tumor caused by a somatic activating mutation of the LH receptor gene in the genomic DNA extracted from tumor material. Not only is this activating mutation of the LH receptor gene present in Leydig cell tumors, but it can also be found in nodular Leydig cell hyperplasia [24]. We detected the same mutation in our patient and till now this mutation exclusively determines the sporadic Leydig cell tumor caused by a somatic activating mutation of the LH receptor gene [25].…”

A single somatic activating Asp578His mutation of the luteinizing hormone receptor causes Leydig cell tumour in boys with gonadotropin‐independent precocious puberty

“…Leydig cell adenomas are the most prevalent hormone‐producing tumours of the testis. Interestingly, a single somatic activating mutation of the LH receptor (LHR), the Asp578His, has been described in a few boys with a rare form of gonadotropin‐independent precocious puberty caused by Leydig cell adenomas or nodular hyperplasia 1–4 . Here we describe the clinical, hormonal and molecular findings of a boy with gonadotropin‐independent precocious puberty caused by a Leydig cell adenoma and compare these findings with the previously reported ones.…”

“…This single somatic Asp578His mutation of the LHR has been almost exclusively found in Leydig cell adenomas of boys with isosexual precocious puberty 1–3 . However, the same somatic mutation was found in a boy with presumable unilateral nodular Leydig cell hyperplasia, although no mature Leydig cells were found in the cranial pole of the testis 4 . In addition, another LHR variant (Tyr113Asn) was found in the tumour and blood DNAs of a boy with Leydig cell adenoma harbouring the Asp578His mutation 2 .…”

Gonadotropin-independent precocious puberty associated with a somatic activating mutation of the LH receptor gene: detection of a mutation present in only a small fraction of cells from testicular tissue using wild-type blocking polymerase chain reaction and laser-capture microdissection

“…This single somatic Asp578His mutation of the LH receptor gene has been described in nine boys, including our case, with gonadotropin-independent precocious puberty caused by Leydig cell tumors [5][6][7][8][9]. In contrast, more than 15 germline mutations causing familial male-limited gonadotropin-independent precocious puberty have been reported [12].…”

“…Leydig cells are the principal source of testosterone, and boys with Leydig cell tumors typically have signs of gonadotropinindependent precocious puberty as a result of testosterone secretion by the tumor. A single somatic activating mutation of the LH receptor gene, Asp578His, limited to tumor cells, has been described in a few boys with gonadotropin-independent precocious puberty [5][6][7][8][9]. Here, we describe a molecular study of a boy with gonadotropin-independent precocious puberty caused by a Leydig cell tumor.…”