Precocious puberty and statural growth

Abstract

Precocious puberty results mostly from the precocious activation of the gonadotropic axis. Although the age limits have recently been discussed, most physicians consider that onset of pubertal development before the age of 8 years in a girl or 9 years in a boy warrants at least a clinical and bone age evaluation by a paediatric endocrinologist. The major concern in precocious puberty is the underlying condition, and central nervous system or gonadal neoplasm have to be formally excluded as a first step in the diagnosis. A secondary concern is height, since precocious puberty leads to accelerated growth, accelerated bone maturation and ultimately reduced stature. Precocious puberty is heterogeneous and strict criteria should be used to define it, both in terms of age and in terms of potential for progression. Depot forms of GnRH agonists are now the standard treatment for progressive central precocious puberty and aim at alleviating the clinical symptoms of early pubertal development, their psychological consequences and the effects on growth. Here, we review the consequences of both central and gonadotropin-independent precocious puberty on adult stature and the information available on outcomes using the therapeutic regimens currently available. In girls with progressive precocious puberty, all published evidence indicates a gain of adult height over height predicted before treatment or over untreated historical controls. However, the apparent height gain (derived from the comparison of predicted and actual heights) is very variable, in large part due to the inaccuracy of height prediction methods. In girls with onset of puberty at the lower half of the normal age (8-10 years) distribution, trials using GnRH agonists have given negative results (no benefit of treatment). In boys, precocious puberty is rare and fewer results are available but point in the same direction. The most appropriate time for interrupting the treatment is still controversial. In conclusion, GnRH agonists restore adult height in children when it is compromised by precocious puberty.

The use of GnRH agonists in precocious puberty

“…Overall, the majority of studies indicate some beneficial effect of GnRHa treatment on final height in girls when compared with initial height predictions (20). The increment can range from 3 to 10 cm, although realistically, a height gain of 4-6 cm after at least 3-4 years of GnRHa treatment is the estimate for a girl with CPP.…”

“…Significant impairment of final height in untreated CPP has dominated the rationale for intervening with GnRH treatment (19). It has been calculated that height loss is of the order of 20 and 12 cm in boys and girls respectively (20). Few studies have evaluated psychosocial outcome following early or precocious puberty, but a long-term Swedish study reported more antisocial behaviour in adolescence and lower academic achievement in adulthood (21).…”

“…The majority of studies compare pretreatment predicted final height data with final attained adult height. The effectiveness of GnRHa treatment can probably only be evaluated by comparing final height data in current treated cohorts with historical data from untreated patients (20).…”

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty

“…The decision to treat depends on the age at onset of puberty, pace of pubertal development, estimated adult height, and psychological impact of the premature sexual development (2,3). Treatment is undisputed in rapidly progressive forms, defined on the basis of clinical, radiological, and biochemical criteria (8), for the significant risk of short adult height, while it is not required in patients with nonprogressive or slowly progressive forms who were shown to achieve an adult height within the normal range without treatment (2,3).…”

“…In the last decades, the widespread use of GnRHa has increasingly demonstrated its favorable effects on statural growth, although the net height gain (HG) associated with the treatment and predictors of long-term outcomes remains debated (2,6,7,8), as no randomized controlled trials (RCTs) have been performed and growth estimation suffers from important methodological limitations, which will be discussed later. Moreover, concerns have been raised on the potential negative effects of treatment on weight and metabolic profile, bone mineral density (BMD), and reproductive function in adulthood (2,3,6).…”