Puberty without Gonadotropins

Abstract

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Nodular Maturation of the Testis

“…4,5,13 While testicular maturation typically occurs in a diffuse fashion throughout the testis in this setting, the maturation can be focal, as has been described in the seminiferous tubules immediately surrounding a Leydig cell tumor or Leydig cell hyperplasia 9,10 or in occasional reports of non-neoplastic cases of gonadotropin-independent precocious puberty; however, those cases do not have a clinically detectable mass. 4,5 The development of nodular maturation in our cohort was mostly idiopathic, although 1 patient did have the McCune-Albright syndrome, which is a known cause of precocious puberty more frequently affecting girls than boys.…”

“…Premature maturation of the testicular parenchyma in young patients is a well-known phenomenon in the setting of precocious puberty, whether central (caused by premature activation of the hypothalamic gonadotropin-releasing hormone pulse generator, so-called “true” or gonadotropin-dependent precocious puberty), from hCG-secreting neoplasms, or due to the peripheral production of androgens by testicular, adrenal, or other neoplasms (so-called “precocious pseudopuberty” or gonadotropin-independent precocious puberty) 4,5,13. While testicular maturation typically occurs in a diffuse fashion throughout the testis in this setting, the maturation can be focal, as has been described in the seminiferous tubules immediately surrounding a Leydig cell tumor or Leydig cell hyperplasia9,10 or in occasional reports of non-neoplastic cases of gonadotropin-independent precocious puberty; however, those cases do not have a clinically detectable mass 4,5. The development of nodular maturation in our cohort was mostly idiopathic, although 1 patient did have the McCune-Albright syndrome, which is a known cause of precocious puberty more frequently affecting girls than boys.…”

“…3 Focal testicular maturation without the formation of a clinically detectable mass has also rarely been reported in association with gonadotropin-independent precocious puberty. 4,5 Similarly, some authors have described maturation of the seminiferous tubules immediately surrounding Leydig cell tumors [6][7][8][9] and Leydig cell hyperplasia. 10 In this study, we describe 8 cases of this ultrasonographic mimic of testicular neoplasia in the pediatric population, with attention to clinical presentation, histopathology, and follow-up status, in an attempt to increase its recognition and prevent unnecessary orchiectomy in these young boys.…”

“…It was later incorporated as an entity in the Armed Forces Institute of Pathology Atlas of Tumor Pathology: Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum, where it was characterized as a focus of maturation of seminiferous tubules and Leydig cells in the prepubertal testis that forms a nodule detectable by ultrasound examination 3. Focal testicular maturation without the formation of a clinically detectable mass has also rarely been reported in association with gonadotropin-independent precocious puberty 4,5. Similarly, some authors have described maturation of the seminiferous tubules immediately surrounding Leydig cell tumors6–9 and Leydig cell hyperplasia 10…”

Effect of Antiandrogen, Aromatase Inhibitor, and Gonadotropin-releasing Hormone Analog on Adult Height in Familial Male Precocious Puberty

“…1–7 The mutation can occur de novo, but is usually inherited as an autosomal dominant. Affected males experience early pubertal development, usually by 3 years of age, with accelerated growth and bone maturation, premature epiphyseal fusion, and short adult stature.…”