Update on the etiology, diagnosis and therapeutic management of sexual precocity

Abstract

Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Gonadotropin-dependent precocious puberty (GDPP) results from the premature activation of the hypothalamic-pituitary-gonadal axis and mimics the physiological pubertal development, although at an inadequate chronological age. Hormonal evaluation, mainly through basal and GnRH-stimulated LH levels shows activation of the gonadotropic axis. Gonadotropin-independent precocious puberty (GIPP) is the result of the secretion of sex steroids, independently from the activation of the gonadotropic axis. Several genetic causes, including constitutive activating mutations in the human LH-receptor gene and activating mutations in the Gs protein a-subunit gene are described as the etiology of testotoxicosis and McCune-Albright syndrome, respectively. The differential diagnosis between GDPP and GIPP has direct implications on the therapeutic option. Long-acting gonadotropin-releasing hormone (GnRH) analogs are the treatment of choice in GDPP. The treatment monitoring is carried out by clinical examination, hormonal evaluation measurements and image studies. For treatment of GIPP, drugs that act by blocking the action of sex steroids on their specific receptors (cyproterone, tamoxifen) or through their synthesis (ketoconazole, medroxyprogesterone, aromatase inhibitors) are used. In addition, variants of the normal pubertal development include isolated forms of precocious thelarche, precocious pubarche and precocious menarche. Here, we provide an update on the etiology, diagnosis and management of sexual precocity.

Central precocious puberty: revisiting the diagnosis and therapeutic management

“…In 40% of the boys, transient pubertal gynecomastia may occur. In both genders, development of pubic hair is associated with adrenarche (10,(16)(17)(18)(19). The stage of female and male pubertal development is determined by Marshall and Tanner's classification (20,21).…”

“…A progression from one stage to another in less than six months and a height velocity above 6 cm/year characterize a progressive condition. Height, weight, and height velocity should be plotted in reference curves, and height is generally found to be above the familial pattern (10,(16)(17)(18)(19).…”

“…However, clinical manifestations below the age of 4 years suggest organic etiologies, particularly hypothalamic hamartomas. Information about family history, including the age at pubertal onset and similar cases in the family, may be useful in the diagnosis of familial CPP (10,(16)(17)(18)(19).…”

“…The physical examination must also investigate the presence of neurofibromas and café-au-lait spots with regular edges, which are suggestive of type 1 neurofibromatosis and related to CPP (associated with optic glioma). Café-au-lait spots with irregular and often jagged edges may indicate the diagnosis of McCune-Albright syndrome, which is associated with peripheral precocious puberty of ovarian etiology (10,(16)(17)(18)(19).…”

“…Clinical indicators of pubertal progression should be carefully conducted in these patients with isolated forms. Laboratory and imaging assessment of isolated variants of puberty can be limited to basal hormonal levels, bone age and pelvic ultrasound in girls (10,16,26).…”