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At a glance

Premature onset of pubertal changes usually defined as onset of menarche in the female before age 8 years or pubertal changes in the male before age 9 years.

Synonym

Central Precocious Puberty.

History

So-called isosexual precocious puberty by Schedewie et al (1981) and Rosenthal et al (1983). It is also described as a syndrome of sexual precocity in boys, characterized by a sex-limited autosomal dominant inheritance pattern and extremely rapid virilization, where increased gonadal testosterone secretion appears to be gonadotropin independent (male-limited precocious puberty or familial male precocious puberty).

Incidence

Estimated incidence in American girls 1 to 2:10,000 with some reports as high as 1:500 in Denmark. The incidence is 15 to 20 times higher in girls than in boys.

Genetic inheritance

In 80 to 90% of girls and approximately 50% of boys with precocious puberty, no causative factor can be found. Precocious puberty is a more frequent occurrence in females than in males, but familial occurrence seems rarer in females. Mutations in the MKRN3 gene on chromosome 19p13.3 have been postulated in familial disease. In males, sex-limited autosomal dominant inheritance was postulated, with the trait transmitted only by affected males to half their sons. In the syndrome of male-limited precocious puberty, the disorder is caused by constitutively activating mutations of the luteinizing hormone receptor gene.

Pathophysiology

There is a premature activation of the hypothalamic-pituitary-gonadal axis as shown by increased secretion of luteinizing hormone and follicle-stimulating hormone. In male-limited precocious puberty, testicular Leydig cell hyperplasia is observed and the resultant virilization results from increased secretion rather than decreased clearance of gonadal testosterone.

Diagnosis

Levels of plasma follicle-stimulating hormone and luteinizing hormone are elevated for the age of the patient. Plasma testosterone (in boys) and estradiol (in girls) are usually elevated to levels consistent with the stage of puberty and osseous maturation. In the syndrome of male-limited precocious puberty, both basal and gonadotropin-releasing hormone-induced secretion of luteinizing hormone is low and there are no suppressive effects of potent gonadotropin-releasing hormone analogues. Advanced spermatogenesis is confirmed on testicular biopsy. Other, nonidiopathic causes for precocious puberty need to be excluded.

Congenital CNS lesions include:

  • Hypothalamic hamartoma

  • Suprasellar arachnoid cysts

  • Hydrocephalus

  • Glioma or neurofibromatosis Type 1

  • Tuberous sclerosis

  • Septo-optic dysplasia

  • Chiari II malformations and myelomeningocele

Acquired CNS lesions such as tumors (astrocytoma, ependymoma, pinealoma, hypothalamic or optic glioma, craniopharyngioma, dysgerminoma, meningioma), granulomatous disease, cerebral palsy, infection, trauma, radiotherapy need to be sought.

Non-CNS lesions such as chromosomal abnormalities, exposure to sex steroids, and adoption need to be considered before assurances can be given.

Clinical aspects

Extremely variable clinical course. Puberty may occur before ...

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