Pretreatment Predicted Adult Height Research Articles

Effect of gonadotropin-releasing hormone agonist treatment in Vietnamese children with central precocious puberty

Gonadotropin-releasing hormone agonists (GnRHa) are generally indicated in central precocious puberty (CPP) patients. We aimed to analyze the auxological outcomes of GnRHa treatment on CPP children. A cross-sectional study with observational data were collected from 143 CPP patients who finished GnRHa therapy in Children Hospital 2, Vietnam. Anthropometry and sexual maturity rating were assessed after 6 months and each year of the therapy. The Bayley-Pinneau method was used to estimate the predicted adult height (PAH). The mean calendar age and bone age at the start of the treatment were 8.0 ± 0.7 years and 10.5 ± 0.1 years, respectively. The mean treatment period was 2.4 ± 0.6 years. GnRHa led to the regression of pubertal symptoms after treatment. The pre-treatment PAH was 157.8 ± 0.6 cm (girls) and 172.3 ± 2.4 cm (boys). The PAH at treatment discontinuation (162.0 ± 0.5 cm in girls and 176.7 ± 2.3 cm in boys) was higher than the initial PAH (p<0.05). For girls with treatment before 6 years old, GnRHa results in a predicted average gain in adult height of 10.2 ± 3.2 cm, whereas the predicted height advancement in the 6-8 age group was 5.3 ± 0.7 cm. The predicted average height gain of girls aged over 8 years was 3.2 ± 0.6 cm. GnRHa therapy was effective for CPP treatment with the improvement of predicted final height. Predicted height advancement was still documented in females who started the treatment after 8 years old.

Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

ObjectiveGonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP.MethodsEighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sexual maturity rating, and predicted adult height (PAH) were assessed every 6 months. Furthermore, 20 boys were followed up after treatment discontinuation until achievement of the final adult height (FAH).ResultsThe mean chronological age (CA) and bone age (BA) of the patients with CPP at treatment initiation were 9.5 ± 0.5 years and 11.7 ± 0.9 years, respectively. The mean duration of treatment was 2.87 ± 0.63 years. The PAH at treatment initiation was 172.1 cm (-0.23 ± 1.05 PAH standard deviation score). The PAH at treatment discontinuation (176.2 ± 6.6 cm) was significantly higher than the pretreatment PAH. In addition, the mean final adult height in the 20 boys who were followed up after discontinuation of treatment was 173.4 ± 5.8 cm, which was significantly higher than the initial PAH (170.1 ± 4.5 cm; p = 0.006). In multivariate analysis, the height gain (the difference between the FAH and PAH at treatment initiation) significantly correlated with the target height.ConclusionLong-term GnRHa treatment significantly improved the growth potential and FAH in boys with CPP.

Histrelin Implantation and Growth Outcomes in Children With Congenital Adrenal Hyperplasia: An Institutional Experience.

BackgroundChildren with congenital adrenal hyperplasia (CAH) because of 21 hydroxylase deficiency (21OHD) are at risk for early or precocious puberty and a short adult height compared to population means and midparental height. The effect of histrelin in suppressing puberty and improving growth in these children has not been reported.MethodsRetrospective cohort analysis of all patients (age ≤ 20) at our institution who underwent histrelin implantation between 2008 and 2017. Treated patients with CAH (classic and nonclassic forms of 21OHD) were identified and their growth data analyzed.ResultsFifteen children with CAH were treated with histrelin for a median of 3 years (range 2–5; age at first implantation 7.7 ± 1.5 years). Bone age (BA) to chronologic age (CA) decreased from 1.57 ± 0.4 to 1.25 ± 0.25 (P < .01), while predicted adult height (PAH) increased by 7.1 ± 6.6 cm (P < .01). A subgroup of 10 children reached adult height. Similar changes in BA/CA and PAH were observed with therapy (P = .02). Adult height z improved compared to pretreatment PAH z (–1.42 ± 0.9 vs. –1.96 ± 1.1 respectively, P < .01), but remained lower than midparental height z (P = .01).ConclusionIn this retrospective cohort study of children with CAH due to 21OHD and early or precocious puberty, histrelin implantation resulted in a decrease in BA progression compared to CA and an improvement in PAH. In the subgroup who completed growth, adult height remained significantly lower than midparental. These results need to be confirmed with prospective controlled studies.

The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

Background. Data on adult height outcomes of the use of Anastrozole and Growth Hormone (GH) in pubertal males with Growth hormone deficiency (GHD) and Idiopathic short stature (ISS) are limited. Objective. We examined the effect of Anastrozole and GH therapy on near adult height (NAH) with pubertal males with GHD or ISS. Methods. Retrospective review of 419 charts from 2008 to 2015. The primary outcomes are NAH compared to mid-parental target height (MPTH) and predicted adult height (PAH). Results. We identified 23 patients (5 SGA/IUGR, 1 Noonan syndrome, 6 GHD, and 11 ISS). Six patients (4 GHD; 2 ISS) achieved NAH. Prior to Anastrozole treatment, the mean chronological age was 13.9±0.2 years (range 13.7–14.4), bone age was 13.6±0.6 years (range 12.5–14), mean height SDS was -1.5±0.5 (range −0.8 to −2.3), and mean PAH was 162.6±5.9 cm (range 153.5–168.6). MPTH was 173.6 cm ± 7 (range 161.8–181.6). Patients received Anastrozole for an average of 30.5 months (range 19–36 months). At NAH, the mean chronological age was 16.7±0.8 years (range 15.9–18.1 years) and height was 170±1.8 cm (range 168.5–173.4 cm). The mean height SDS improved to +0.81±0.6 (range +0.08 to +1.92, p=0.002). Net height gain was 7.3 cm compared to pretreatment PAH (p&lt;0.01) and overall the mean adult height remained 3.5 cm below MPTH. Conclusion. Anastrozole and GH therapy can be effective in augmenting adult height without significant side effects. However, the long-term safety and efficacy of aromatase inhibitor use in pediatrics remain limited.

Adult height, body mass index and time of menarche of girls with idiopathic central precocious puberty after gonadotropin-releasing hormone analogue treatment

Background. Long-term outcome data of central precocious puberty (CPP) girls treated with gonadotropin-releasing hormone analogue (GnRHa) are conflicting.Aim. To assess long-term outcome of girls with idiopathic CPP (iCPP) treated with GnRHaMethods. We compared adult height (AH), body mass index (BMI) and time of menarche in GnRHa-treated (n = 47) and untreated (n = 11) girls with iCPP.Results. There were no differences in age, bone age, height, weight and BMI z-scores, predicted adult height (PAH) at the time of diagnosis and target height between the two groups. Mean (SD) age of GnRHa-treated girls was 8.5 (1.0) years at the start of treatment. Mean (SD) AH of the treated group was greater [158.6 (5.2) vs. 154.8 (5.6) cm], p < 0.05. AH gain over pre-treatment PAH in the treated group was 4.7 cm. BMI z-score of treated girls was 1.26 (0.95) before the treatment initiated and returned to normal [0.16 (1.0)] at the time of AH reached. Menstruation occurred at 0.9 (0.5) years following GnRHa discontinuation with regular pattern.Conclusions. Long-term GnRHa therapy has a modest beneficial effect on adult height gain in girls with iCPP. No detrimental effects on increasing BMI and hypothalamic–pituitary–gonadal axis reactivation are demonstrated.

Long-Term Observation of 87 Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogs: Impact on Adult Height, Body Mass Index, Bone Mineral Content, and Reproductive Function

We assessed in a retrospective unicenter study the impact of treatment with GnRH analogs (GnRHa) on adult height (AH), body mass index (BMI), bone mineral density (BMD), and reproductive function in girls with idiopathic central precocious puberty (ICPP). Eighty-seven ICPP patients were treated with GnRHa for 4.2 +/- 1.6 yr (range 3-7.9) and observed for 9.9 +/- 2.0 yr (range 4-10.6 yr) after discontinuation of treatment; to estimate the efficacy better, 32 comparable ICPP untreated girls were analyzed. AH was 159.8 +/- 5.3 cm, significantly higher than pretreatment predicted AH (PAH) either for accelerated or for average tables of Bayley and Pinneau. The gain in centimeters between pretreatment PAH and AH was 5.1 +/- 4.5 and 9.5 +/- 4.6 cm, respectively. Hormonal values and ovarian and uterine dimensions, reduced during treatment, increased to normal after 1 yr without therapy. Age of menarche was 13.6 +/- 1.1 yr with an interval of 0.9 +/- 0.4 yr after therapy. Menstrual pattern was normal. Six girls became pregnant and delivered normal offspring. BMI sd score for chronological age increased, but not significantly, before, during, and after therapy. BMD at discontinuation of treatment was significantly lower and increased to control values after gonadal activity resumption. GnRHa treatment in ICPP is safe for the reproductive system, BMD, and BMI and helpful in reaching AH close to target height; however, the variability of individual responses suggests that one choose more parameters than increment in height, especially in girls with pubertal onset over 8 yr of age.

Final Height in Girls With Central Idiopathic Precocious Puberty Treated With Gonadotropin-Releasing Hormone Analog and Oxandrolone

Central precocious puberty (CPP), the onset of sexual development before age 8 in girls, reflects early activation of the hypothalamic-pituitary-gonadal axis and currently is treated with a gonadotropin-releasing hormone analog (GnRHa). One of the goals of such treatment is to slow bone maturation and thereby increase final adult height. Some patients, however, grow at a less than optimal rate and become short-statured as a result. This open-label study was carried out in 20 girls with CPP who experienced marked growth deceleration (height velocity below the 25th centile for age) during GnRHa treatment. All of them continued to receive 3.75 mg Leuprorelina intramuscularly at monthly intervals. Ten girls (group 1) also received, by mouth, 0.06 mg/kg daily of the androgen oxandrolone (Ox). The remaining 10 girls (group 2) continued to receive only the GnRHa. The groups were matched for chronologic age, bone age, the duration of GnRH analog treatment (averaging 5 years), and the degree of growth deceleration. In both groups, plasma concentrations of luteinizing hormone and follicle-stimulating hormone remained suppressed, rising to appropriate levels within 18 months of the time that GnRHa treatment stopped. Menarche occurred an average of 16 and 18 months after treatment stopped in groups 1 and 2, respectively. Bone age progressed regularly in both groups. When GnRHa treatment began, predicted adult height (PAH) in patients in group 1 did not differ significantly from that recorded at the time Ox was added. At the end of combined treatment, PAH was significantly higher than at the time of diagnosis and at the start of GnRHa therapy. Final height significantly exceeded target height in patients in group 1, was similar to the PAH at the end of treatment, and was significantly higher than when GnRHa treatment began. In patients in group 2, PAH at the start of treatment did not differ significantly from that at the time GnRHA therapy ended. Their final height was similar to the PAH at both the beginning of treatment and its end. Target height was not reached and it significantly exceeded final height. The gap between pretreatment PAH and final height in patients in group 1 differed significantly from that in patients in group 2 (7.8 vs -3.8 cm). The same was the case for the difference between final height and target height (4.6 vs -4.2 cm). No adverse effects were noted in either treatment group. Treatment did not alter circulating levels of insulin-like growth factor I. Adding oxandrolone to GnRHa treatment in girls with idiopathic CPP whose growth has markedly decelerated improves final height without causing significant side effects. In the present study, combined treatment permitted the girls to reach a final height greater than the target height. This was not the case for girls who continued to receive only GnRHa whose final height was lower than target height.

Combined therapy with GnRH analog plus growth hormone in central precocious puberty.

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and therefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA), ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa treatment who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of the addition of GH. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters obtained calculated between pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRH analogue while in patients treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. In conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies the addition of GH for 2-3 yr to conventional treatment with GnRH analogues in patients with central precocious puberty, and with a decrease in growth velocity so marked as to impair predicted adult height to below the third percentile.

Increase in Near-Final Height in Short Non-Growth Hormone Deficient Children Treated with Growth Hormone

The Genentech Study Group has treated patients with severe short stature (height <-2 SD score (SDS) not due to classically defined GH deficiency with up to seven years of GH treatment (0.3mg/kg/wk). Of the initial 121 patients, 33 have achieved near final height, with bone age (BA) ≥16 years for boys and ≥14 years for girls. At this bone age greater than 98% of adult height has been achieved. The mean difference between the first available pretreatment predicted adult height (PAH) and the PAH at near final height (Δ PAH) was 4.0cm for the boys and 8.1cm for the girls. We compared these changes in PAH achieved with GH treatment of these short non-GH deficient patients with the changes seen in 33 untreated normal children from the Fels Longitudinal Growth Study whose height was below -1 SDS for age, and to 19 historical controls followed in our clinics whose height was below -2 SDS for age at presentations who were not treated with GH. The differences in Δ PAH achieved by the GH treated patients compared to the -1 SDS controls were 5.7cm for boys and 4.5cm for girls. When compared to the <-2 SDS controls the differences in PAH were 8.2cm for boys and 7.7cm for girls. We conclude that GH treatment of patients with marked short stature does result in an increase in their mean final height. However, these patients did not achieve their mean mid-parental target height.

Growth hormone treatment of idiopathic short stature.

Considerable controversy exists about the use of growth hormone (GH) treatment in short children without classical GH deficiency (idiopathic short stature or ISS). ISS is a multifactorial disorder with many potential causes rather than a single diagnostic entity, and it is in essence a diagnosis of exclusion. A careful investigation of the components of the GH/insulin-like growth factor (IGF) axis and other potential causes of short stature must be carried out in patients with significant short stature before they are categorized as having the ISS syndrome. As a group, most patients with ISS can be expected to attain an adult stature within the normal range. The ISS patients who will not do so are generally those who have a poor initial predicted adult height (PAH) and present at a younger age. Those ISS patients with a shorter midparental height are also less likely to achieve a normal adult height. In addition, several studies have shown that, as a group, males with ISS do not attain their initial PAH. Most studies on the GH treatment of patients with ISS have shown a short-term increase in growth rate and relative height. However, the long-term outcome of GH treatment of ISS has been variously reported to be no significant change, a slight increase, or a significant increase. One of the largest and most optimistic experiences with GH treatment of ISS is the collaborative US study sponsored by Genentech. This group has treated 121 patients with ISS not due to classically defined GH deficiency for up to 9 years with GH (0.3 mg/kg per week). A total of 51 of these patients has now reached near final height, with bone age (BA) > or = 16 years for boys and > or = 14 years for girls. The mean difference between the first available pretreatment PAH and the PAH at near-final height (delta PAH) was 5.7 cm for the boys and 6.5 cm for the girls. The strongest predictors of response to treatment available before the start of GH treatment were bone age and pretreatment PAH. The increase in height seen with GH treatment of ISS was not enough to increase the mean expected final height to the midparental target height, or to completely correct a low pretreatment PAH. Whether this increase in expected final height in ISS patients with GH treatment is due to a correction of a subtle abnormality of GH secretion or action, or to the pharmacological effects of GH is unclear. The decision to use GH treatment in ISS is a complex issue which must involve the accuracy of the diagnosis of GH deficiency or abnormality in the GH/IGF axis, the PAH and BA of the patient, the potential benefits, and economic issues for the medical care system. In general, GH treatment should only be considered in young ISS patients with poor initial PAH and height prognosis, and GH treatment of older patients who have a normal PAH is not justified.