Author(s): John S Fuqua
Precocious puberty is a common problem affecting up to 29 per 100 000 girls per year. The earliest identified neuroendocrine change in early puberty thus far is increased kisspeptin secretion from the arcuate nucleus and the anteroventral paraventricular nucleus of the hypothalamus. The regulation of kisspeptin secretion is not well understood, but neurokinin B and dynorphin provide autocrine regulation. The etiologies of precocious puberty may be subdivided into GnRH-dependent and GnRH-independent causes. GnRH-dependent precocious puberty, often called central precocious puberty (CPP), is usually treated with GnRH analogs. Newer developments in the treatment of CPP include expanded data on the safety and efficacy of the subdermal histrelin implant, which is useful for long-term treatment, although removal may be difficult in some cases. Preliminary data suggest that the implant may be left in place for up to 2 years without loss of biochemical suppression. In the last 2 years, more data have been published concerning extended-release leuprolide acetate injections that indicate that the 11.25-mg dose may not provide full biochemical suppression but may clinically suppress signs of puberty, including the accelerated growth velocity and advanced skeletal maturation seen in CPP. Treatment options for familial male-limited precocious puberty and McCune-Albright syndrome are expanding as well, although data are preliminary. Long-term outcome studies of CPP indicate overall good menstrual and reproductive function, but the prevalence of polycystic ovary syndrome may be higher than in the general population. Remarkably few studies have evaluated the behavioral and psychological outcomes of precocious puberty, in contrast to early normal maturation. Additional outcome studies of endocrine, metabolic, and psychological effects of CPP are clearly needed. Precocious puberty is one of the more common conditions encountered in pediatric endocrinology practice. New articles about increasingly early pubertal development have appeared in the lay press, making families' questions about their children's pubertal development increasingly common. Over the last 2 years, new information has become available, particularly related to therapies and outcomes, making an update in this field timely. Precocious puberty can be defined as sex hormone production or exposure occurring earlier than the norms for gender and racial or ethnic background. Just how common is precocious puberty? On the basis of a population-based registry, the prevalence of all forms of precocious puberty in Denmark has been estimated as 0.2% of girls and < 0.05% of boys. The annual incidence of precocious puberty in girls varied over an 8-year period from 15–29 per 100 000 girls. The incidence in boys was approximately 10- to 15-fold lower (1). These figures include those with the variants of premature thelarche (PT), premature adrenarche (PA), and early normal maturing children in addition to those with true central precocious puberty (CPP), which made up 46%. More recently, estimates from a broad hospital-based registry in Spain put the annual incidence of CPP in girls at 1.1 per 100 000 (2). Although this seems much lower than the Danish study, there were significant methodological differences, including restricting data collection to tertiary care centers with pediatric endocrinology services, inclusion of only those with CPP, and a more stringent definition of precocious puberty. This paper will briefly review the changes typically seen during pubertal development in normal children and some of the neuroendocrine mechanisms regulating this process. Just how early is too early for puberty has been the subject of much debate. Space constraints prevent a detailed discussion of this controversy, but some recent articles will be reviewed. The focus will then shift to precocious puberty, with an emphasis on recent progress in its treatment and our understanding about outcomes.