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Premature onset of pubertal changes.

So-called isosexual precocious puberty is usually defined as onset of menarche in the female before age 8.5 years or pubertal changes in the male before age 10 years. Schedewie et al. (1981) and Rosenthal et al. (1983) also described 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).

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. 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.

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.

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.

Extremely variable clinical course. Puberty may occur before 3 years of age. Affected children may complete sexual maturation rapidly or slowly. Adult height is reduced as the increased rate of ossification results in early closure of the epiphyses. Dental age and mental development are usually compatible with chronologic age. Hypothyroidism is occasionally accompanied by precocious puberty and thyroid function should be checked and if it is the case, treatment should be administered in these patients. Otherwise, treatment consists mainly of psychological support of the patient and family. Sexual precocity, fibrous dysplasia, and patchy pigmentation occur in McCune-Albright syndrome where hyperthyroidism is common. Precocious puberty may also result from organic brain lesions such as hypothalamic hamartomas. Signs of increased intracranial pressure may surface years later. Computed tomography scan of the head is indicated in all boys with true precocious puberty when no specific cause can be found. In boys, other causes of the precocity should be evaluated, including adrenogenital syndrome, Leydig cell tumor, and gonadotropin-producing hepatoma.

In patients in whom precocity arises as the result of intracranial lesions, examine for signs of increased intracranial pressure. Determine thyroid function status; patients on thyroxine replacement for hypothyroidism should have the therapy ...

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