Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

Abstract

PurposeThere is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP.MethodsWe reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23).ResultsIn the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm) was significantly higher than the initial PAH (156.6±3.96 cm) (P<0.001), and it was similar to the MPH (159.9±3.52 cm). In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm) was also higher than the initial PAH (154.6±2.55 cm) (P<0.001), which was similar to the MPH (158.1±3.31 cm). Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.ConclusionIn CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

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

“…The great majority of patients reached an adult height consistent with the TH (13,14,15,17,18,19,20,21,22,23,24,25), a minority of them did not reach the TH (19,26), and a very small portion of patients remained shorter than the predicted height before treatment (13,27). Discordant results were obtained when comparing the efficacy of treatment in females and males.…”

“…Elevated height (or height SDS) before (16,17,19,20,24,30) and at the withdrawal of treatment (12,16,17,19,20,25,30), as well as high TH (or TH-SDS) (17,20,21,23,30), has also been positively associated with adult height, supporting the primary influence of genetic factors in the determination of adult height even in patients treated with GnRHa (20).…”

“…Few studies (12,26) showed no correlation between HG and age at puberty onset or initiation of treatment, suggesting that girls with late onset CPP benefit from treatment similarly to girls with earlier pubertal onset (12). A longer treatment duration appears to be a positive outcome predictor in the majority (19,20,21,24,30), although not all (15,23), of the studies, together with a short interval between pubertal onset and the start of treatment (24,30), a great growth spurt after the end of treatment (12), low pre-treatment estradiol levels (30), and advanced BA at the start of treatment (14,18,19,20,21,25). The impact of advanced BA at the start of treatment on adult height was not documented in the study by Brito et al (30), whereas Carel et al (12) found a negative association between the BA/statural age ratio at the onset of treatment and adult height suggesting that treatment is not capable of restoring a full adult height potential if started after an irreversible advancement of BA.…”

“…5 years (15,22)) and of treatment (i.e. 6 years (18,20,21,23,24,25)) are associated with a taller adult stature. In a study by Klein et al (24) performed in 98 patients (F:MZ80:18) treated with histrelin or deslorelin, the average adult height and HG (14.5G9.9 cm vs 6.8G6.9 cm; P!0.001) were greater in girls with puberty onset !6 years of age than those with onset of puberty between 6 and 8 years of age.…”

“…According to two independent studies (33,37) analyzing normal-weight and overweight children separately, BMI-SDS during treatment increased in normalweight children, whereas it remained stable in overweight subjects. The majority of long-term studies showed an increased prevalence of overweight and obesity in patients with CPP at diagnosis (22,38), but no significant mean or individual BMI-SDS changes were shown at the end of treatment, irrespective of sex, age at puberty onset and at the start and discontinuation of treatment (15,17,22,23,24,25,30,32,39), and type of GnRHa (31). Recently, a study by Colmenares et al (39) evaluated the effects of GnRHa in treated (nZ29) and untreated (nZ8) CPP patients and in treated (nZ14) and untreated (nZ20) rapidly progressing early puberty (EP), during a 3-year follow-up period.…”