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

Abstract

It has been recently shown that male LH-independent sexual precocity is caused by a somatic activating mutation in the luteinising hormone receptor (LHR) of Leydig cell tumours. In each of the patients described to date, the tumour was a well-defined, single encapsulated nodule. We present a 5.7-year-old boy with nodular Leydig cell hyperplasia, who harbours a somatic mutation of the LHRgene. The boy showed the clinical features of severe sexual precocity caused by LH-independent testosterone hypersecretion. Congenital adrenal hyperplasia, hCG- or androgen-secreting tumours, McCune-Albright syndrome, and familial male-limited precocious puberty (or testotoxicosis) were all ruled out as possible causes. A hypoechoic area was detected at the cranial pole of his right testis and a biopsy was performed. Histological examination revealed a lack of mature Leydig cells. When DNA from the affected tissue was isolated and sequenced, no somatic mutation of the LHR gene was found. To further determine the origin of the elevated testosterone levels, venous sampling was performed. Blood samples taken from the right spermatic vein showed an elevated serum testosterone concentration of 259 nmol/l. Unilateral orchiectomy of the right testis was performed, and systemic testosterone concentrations normalised. Histological examination revealed nodular Leydig cell hyperplasia. DNA analysis of the nodular tissue showed a heterozygous mutation in exon 11 of the LHR gene, which caused the replacement of aspartic acid at codon 578 by histidine. 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.