Testicular Leydig Cell Hyperplasia as a Cause of Familial Sexual Precocity*

Abstract

Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.

Luteinizing hormone receptor mutations in disorders of sexual development and cancer

“…Signs of puberty usually appear by 3-4 years of age in boys with FMPP (43). Histologic examination of testicular biopsy shows hyperplasia of Leydig cells (17). Affected boys have secondary sexual development with penile growth and bilateral enlargement of testes and pubic hair development indistinguishable from true puberty (44).…”

“…This autosomal dominant condition is termed familial male-limited precocious puberty (FMPP) (17) or testotoxicosis (18). Sporadic cases caused by new mutations of the LHR are called sporadic male-limited precocious puberty (SMPP).…”

Mutações ativadoras do gene do receptor do hormônio luteinizante em meninos com testotoxicose

“…Two Brazilian women, including a prepubertal girl with activating mutations, were asymptomatic and had normal hormonal profile. A PUBERDADE PRECOCE FAMILIAL de acometimento restrito ao sexo masculino, também conhecida como testotoxicose ou pela sigla FMPP (familial male-limited precocious puberty), é uma forma rara de desenvolvimento isossexual precoce em meninos (1)(2)(3). Esta condição genética de herança autossômica dominante é caracterizada por níveis elevados de testosterona, independentes da regulação do eixo hipotálamo-hipofisário (2,3).…”

“…Esta condição genética de herança autossômica dominante é caracterizada por níveis elevados de testosterona, independentes da regulação do eixo hipotálamo-hipofisário (2,3). Portanto, níveis puberais de testosterona estão associados a valores pré-puberais ou mesmo suprimidos das gonadotrofinas, indicando uma anormalidade de origem testicular (1,2).…”

“…Os caracteres sexuais secundários aparecem freqüentemente nos primeiros quatro anos de vida nos meninos com testotoxicose (1)(2)(3). O fenótipo, caracterizado pelo aumento testicular, virilização exagerada e aceleração do crescimento linear e da idade óssea, é decorrente do aumento da produção androgênica pelas células de Leydig hiperplasiadas (3).…”