Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution

Out of 35 girls with idiopathic central precocious puberty (CPP) treated with gonadotropin-releasing hormone agonist (GnRHa) (depot-triptorelin) at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 years whose growth velocity fell below the 25th percentile for chronological age (CA), 17 received growth hormone (GH) in addition at a dose of 0.3 mg/kg/week, s.c., 6 days per week, for 2-4 years. The other 18, matched for bone age (BA), CA and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, remained on GnRHa alone, and were used as a control group to evaluate GH efficacy. No patient was GH deficient. Both groups discontinued treatment at a comparable BA (mean +/- SD): BA 13.4 +/- 0.6 in GnRHa plus GH group vs 13.0 +/- 0.5 years in the GnRHa alone group. The 35 patients have reached adult height (i.e. growth during the preceding year was less than 1 cm, with a BA of over 15 years). Patients of the group treated with GH plus GnRHa showed an adult height (161.2 +/- 4.8 cm) significantly higher (p < 0.001) than pre-treatment predicted adult height (PAH) calculated according to tables either for accelerated girls (153.2 +/- 5.0 cm) or for average girls (148.6 +/- 4.3 cm). The adult height of the GnRH alone treated group (156.6 +/- 5.7) was not significantly higher than pre-treatment PAH if calculated on Bayley and Pinneau tables for accelerated girls (153.9 +/- 3.8 cm), whilst it remained significantly higher if calculated on tables for average girls (149.6 +/- 4.0 cm) (p < 0.001). The gain between pre-treatment PAH and final height was 8.2 +/- 4.8 cm according to tables for accelerated girls and 12.7 +/- 4.8 cm according to tables for average girls in patients treated with GH plus GnRHa; while in patients treated with GnRH alone the gain calculated between pre-treatment PAH for accelerated girls was just 2.3 +/- 2.9 cm and 7.1 +/- 2.7 cm greater than pre-treatment PAH for average girls. The difference between the gain obtained in the two groups (about 6 cm) remained the same, however PAH was calculated. The addition of GH to GnRHa in a larger cohort of patients with CPP with a longer follow-up confirms the safety of the combined treatment and the still significant but more variable gain in the group with the combined treatment, probably due to the larger number of patients analyzed. Caution is advised in using such an invasive and expensive treatment, and there is need for further studies before widespread clinical use outside a research setting.     

Use of growth hormone and gonadotropin releasing hormone agonist in addition to L-thyroxine to attain normal adult height in two patients with severe Hashimoto's thyroiditis

AIM: We report two patients with severe acquired juvenile hypothyroidism who presented with compromised predicted adult height (PAH), and the successful use of growth hormone (GH) and gonadotropin releasing hormone agonist (GnRHa) in addition to L-thyroxine to attain normal adult height. PATIENTS AND RESULTS: Patient 1: 13 year-old girl who presented with pubertal delay, short stature (height SDS -4), and marked bone age retardation (BA 8 yr). Serum T4 was undetectable and TSH level was 1,139 mIU/l. After 1 year of treatment with L-thyroxine, growth rate improved from 1.0 cm/yr to 9.8 cm/yr but puberty progressed (Tanner 3 breast) and BA accelerated by 4 years, compromising predicted adult height (PAH) (144 cm vs mid-parental target height [MTH] of 163 cm). Combined use of GH and GnRHa for one year slowed BA progression, and catch-up growth (10.4 cm/yr) continued to attain a final height (FH) of 155 cm. Patient 2: 14 year-old boy with undetectable T4, TSH of 811 mIU/l in mid-puberty with poor growth rate (1.0 cm/yr), without any bone age delay (BA 14 years) but compromised PAH (163.8 cm vs MTH 174 cm). Because of the advanced puberty and poor growth rate, treatment with GH and GnRHa was initiated. Treatment for 2 years led to improvement of growth velocity (10.6 cm/yr), slowed BA progression to attain a FH equal to MTH. CONCLUSION: Combined use of GH and GnRHa improved the FH of two patients, with Hashimoto's thyroiditis: one with pubertal and bone age delay and the other with normal onset of puberty and normal bone age.     

Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height

OBJECTIVE: This study was conducted to study the role of combination therapy of growth hormone and Gonadotropin-releasing hormone (GnRH) analogues in girls with idiopathic central precocious puberty (CPP) or idiopathic short stature (ISS). METHODS: Five girls with CPP (median age 9.1 y, pubertal stage 2-3) (3 of them previously treated with GnRH analogue (GnRHa) for 16.2 +/- 0.3 months) and 8 girls with ISS (median age 11.4 y, pubertal stage 2-3) (previously treated with GH for 10.95 +/- 1.42 months), were treated with recombinant human GH (0.33 mg/kg/week) and GnRHa (3.75 mg/28 days) for 22 months. RESULTS: Height of girls with CPP improved from - 1.3 to - 0.2 SDS and height for BA from - 2.1 to - 0.6 SDS (P = 0.042). Predicted adult height (PAH) improved from - 3.1 to - 0.6 SDS (P = 0.042). In girls with ISS only PAH improved from - 3.0 to - 1.5 SDS (P = 0.025). CONCLUSION: Combined treatment improves height and PAH in CPP. Height in ISS is also improved however not significantly.     

Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin suppressive effect and final height obtained with two different analogs

OBJECTIVES: To distinguish which children with precocious puberty (PP) and early puberty (EP) should be treated and which followed without therapy. To determine the effect of GnRH analog treatment on the final height of treated patients and compare the effect of two different analogs on gonadotropin suppression and final height. STUDY DESIGN: Sixteen females with PP or EP with a mean chronological age (CA) of 8.8 +/- 1.4 years and a mean bone age (BA) of 10.8 +/- 1.3 years were treated for a mean of 2.7 +/- 1.0 years with a GnRH analog (triptorelin or leuprolide acetate; group A), while 21 girls with a mean CA of 8.5 +/- 1.0 years, a mean BA of 9.7 +/- 1.4 years and a predicted adult height of >155 cm were followed without therapy (group B). Criteria for treatment were one of: a. predicted adult height (PAH) of <155 cm initially or at any time during follow up; b. PAH over 155 cm with a dramatic decrease in PAH over a 6-month follow-up period; c. advanced and rapidly progressing breast development for age (Tanner 3 before the age of 9 years). RESULTS: GnRHa therapy suppressed gonadotropins in group A, while gonadotropins increased gradually in group B. Height velocity (HV) decreased in group A, while it remained accelerated in group B; BA increased a mean of 1.7 +/- 0.5 years in group A and 3.2 +/- 0.3 years in group B. This resulted in a height increase in group A from a baseline PAH of 153.7 +/- 1.2 cm to a final height (FH) of 160.9 +/- 4.0 cm (p <0.001), clearly above their target height (TH) of 157.7 +/- 4.2 cm. The height of group B children did not change over time (164.1 +/- 4.1 cm before therapy and 166.0 +/- 6.0 cm at FH), both above their TH. The mean leuprolide acetate dose utilized in this study decreased during treatment, while both the initial and final triptorelin dose remained unchanged. Adequate gonadotropin suppression (peak level of LH and FSH of <2 IU/l after i.v. GnRH stimulation) was noted with both leuprolide acetate and triptorelin, although LH suppression was slightly more pronounced with triptorelin. BA advanced 1.8 +/- 0.4 years during leuprolide acetate treatment and 1.5 +/- 0.3 years with triptorelin, so that FH increased a mean of 5.5 +/- 1.3 cm with leuprolide acetate and 8.7 +/- 2.2 cm with triptorelin. CONCLUSIONS: PAH of <155 cm before or during therapy, PAH of >155 cm with a dramatic decrease in predicted height over a 6-month follow-up period and/or advanced and rapidly progressing breast development in girls with PP or EP were useful parameters in deciding which patients to treat. GnRHa therapy suppressed gonadotropins, HV and bone maturation in children with an accelerated form of PP or EP, resulting in a significant height increase. Final height remained stable over time in untreated patients. Adequate gonadotropin suppression was noted with both analogs, although with the doses of analog used in our study, LH and BA suppression were more pronounced with triptorelin, resulting in a larger height gain.     

Treatment of central precocious puberty: lessons from a 15 years prospective trial. German Decapeptyl Study Group

There is still controversy about the auxological outcome of GnRH agonist treatment in patients with CPP and about the favorable age and auxological characteristics at start of treatment for achieving a normal final height (FH) or for preserving height potential. We analyzed the FH data of 52 young women from a prospective multicentric trial which was started in 1985. The aim of this analysis was to determine factors that may predict a favorable FH or a good height gain. Chronological age (CA) was 5.2 +/- 2.1 yr (+/- SD) at start of puberty, 6.2 +/- 2.0 yr at start of triptorelin depot treatment, 11.1 +/- 1.1 yr at end of treatment, and 16.7 +/- 2.6 yr at FH evaluation. After 4.8 +/- 2.2 yr (1.1-9.9 yr) of treatment duration, FH was 160.6 +/- 8.0 cm (vs 154.9 +/- 9.6 cm of initial height prediction [PAH], p<0.05). A FH within TH range or in excess of mean TH was achieved by 78% or 41% of patients. FH was above the 3rd percentile of the normal German population in 29% of patients (63% had an initial PAH < 156 cm). The group of patients with start of puberty at age < or = 6 yr (Group 1) showed a significantly higher height gain (FH - initial PAH) and lower height deficit compared to TH than older patients (Group 2). Furthermore, the percentage of patients from Group 1 reaching TH range or mean TH showed a significant increase with GnRH agonist treatment whereas this was not the case in Group 2. Stepwise regression analysis showed that height SDS at end of treatment, age at menarche, bone age (BA) at start of treatment, and BA advancement at end of treatment were determinants of FH (r2=0.923). Initial BA advancement and treatment duration were the factors that explained 68% of the variability of height gain. Although BA advancement at initiation of treatment was negatively associated with FH it was a positive predictor of height gain. In addition, height gain correlated significantly with CA and BA at start of treatment (r= -0.430, p=0.004 and r=0.359, p=0.018). Growth after interruption of treatment had no significant predictive effect on FH. It is concluded that a higher percentage of patients below 6 yr of age at start of puberty do profit from GnRH agonist treatment with respect to achieving a normal FH. BA, BA advancement, and height SDS at treatment start are important factors for determining outcome.     

Catch-up growth in severe juvenile hypothyroidism: treatment with a GnRH analog

Anecdotal reports suggest that the addition of a gonadotropin releasing hormone (GnRH) analog (GnRHa) in addition to L-thyroxine (LT4) replacement may increase adult stature in children with severe longstanding hypothyroidism by prolonging the pubertal growth period. This retrospective chart review compares the height outcome and body mass index in 33 children (21 treated with LT4 alone and 12 treated with LT4 + GnRHa) with severe longstanding hypothyroidism and bone age delay. Seventeen controls and six GnRHa-treated patients were followed to adult height (BA >14 yr [F]/16 yr [M] and/or growth velocity < 2 cm/yr). At diagnosis, GnRHa-treated patients were 1) older and shorter for chronological age, and 2) more advanced in puberty and bone age. Despite these differences, at adult height, both groups had similar improvements in height Z scores, similar height deficits, and comparable adult heights. Changes in BMI Z score were similar for both groups. Our study suggests that the addition of GnRHa to LT4 may improve interval growth without imposing a risk of obesity in children with longstanding severe hypothyroidism.     

GnRHa治疗中枢性性早熟女童对终身高的影响

目的：观察促性腺激素释放激素类似物（GnRHa）对治疗中枢性性早熟（central precocious puberty,CPP）女童终身高的作用及相关因素。方法：对26例CPP女童应用GnRHa治疗前后预测身高、骨龄的标准差分值［HtSDS(BA)］、终身高、体重指数（BMI）、初潮情况等进行评价,分析它们与终身高的相关性。结果：治疗前预测身高为151.5±5.7 cm;停药时预测身高为158.4±5.2 cm;终身高为158.0±4.0 cm,高于靶身高155.3±4.4 cm (P<0.01)。终身高与初始身高、预测身高、HtSDS(BA)正相关。治疗前BMI为17.1±2.1、治疗后BMI为19.9±3.2,两者呈正相关。停药后平均13.2±6.1个月后初潮,平均初潮年龄为12.2±0.7岁。结论：GnRHa治疗CPP可有效地改善终身高,终身高与治疗前身高及预测身高等密切相关,停药后患儿青春发育与正常儿童相似。［中国当代儿科杂志,2009,11（5）：374-376］     

Long-term treatment with GHRH [1-44] amide in prepubertal children with classical growth hormone deficiency.

A cohort of 20 GH deficient prepubertal patients were treated with GHRH [1-44] 10 micrograms/kg or 20 micrograms/kg twice daily for up to four years (5 patients). GHRH treatment resulted in sustained improvement in height velocity. The mean prepubertal height velocity was 3.57 +/- 1.05 cm/yr pretreatment; 8.49 +/- 1.45 cm/yr at year 1; 6.86 +/- 1.45 cm/yr at year 2; 6.22 +/- 0.74 cm/yr at year 3; and 6.16 +/- 0.97 cm/yr at year 4. IGF-I levels increased and remained within normal range. The difference between the children's and the parents' Ht SD scores significantly diminished from a pretreatment difference of -2.43 to -0.48 after four years of treatment. No adverse effects were noted during treatment. We conclude that twice-daily GHRH [1-44] treatment in a small group of prepubertal GH deficient children resulted in sustained improvement in height and growth velocity, and achieved height SDS approaching closely those of their parents.     

Factors influencing final/near-final height in 12 boys with central precocious puberty treated with gonadotrophin-releasing hormone agonists. Italian Study Group of Physiopathology of Puberty

Gonadotrophin-releasing hormone agonists (GnRHa) have been demonstrated as the therapy of choice for central precocious puberty (CPP). Few studies have provided male patients' adult height data. In our multicenter study we evaluated long-term effects of different GnRHa preparations and final/near-final height (FH) in 12 boys with CPP and analyzed the factors influencing FH. Patients' mean chronological age at the time of diagnosis was 7.6 +/- 0.9 yr. Three patients were treated only with triptorelin at a mean dose of 90 microg/kg i.m. every 28 days. Nine patients initially received buserelin (at a mean initial dose of 53.4 microg/kg/day i.n. divided into 3-6 equal doses) or buserelin (at a mean dose of 36.7 microg/kg/day s.c.) and were subsequently switched to triptorelin. The GnRHa therapy was continued for 4.1 +/- 0.6 yr (range 2.9-5.4). The mean predicted adult height increased from 169.9 +/- 4.2 cm at diagnosis to 180.7 +/- 6.0 cm at the end of treatment. Mean FH was 176.1 +/- 6.1 cm (170.1-190.7), corresponding to mean SDS(CA) 0.4 +/- 0.8 (-0.6/2.5), mean SDSBA 0.2 +/- 0.9 (-0.6/2.4) and mean corrected SDS for target height of 0.4 +/- 0.6 (-0.8/1.2). Multiple regression analysis revealed that FH was mainly influenced by target height and height at discontinuation of GnRHa therapy. The present data indicate that GnRHa therapy significantly improves growth prognosis in boys with CPP and fully restores genetic height potential.     

Near final height after GnRH agonist treatment in central precocious puberty

The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.     

When to stop GnRH analog therapy: the experience of the Italian Study Group for Physiopathology of Puberty

Data reported in this study have been recently published elsewhere. The authors retrospectively analyzed the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP), who had been treated with the same therapy protocol (Decapeptyl Depot at the dose of 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0 +/- 1.3 yr) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: A) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, p<0.01); B) a striking deceleration of BA, revealed by the subnormal deltaBA:deltaCA ratio (0.2 +/- 0.1); C) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, p<0.0005). Treatment interruption was followed by notable catchdown growth, with FH (158.4 +/- 5.8 cm) lower (p < 0.025) with respect to that predicted at the end of therapy. However FH fell within the population norm and the target range in 87.3% and 90% of patients, respectively. The tallest FH was recorded in the patients who discontinued treatment at a BA of 12.0-12.5 years. We conclude that: 1) Most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; 2) The height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; 3) The most favorable height prognosis with respect to target height (TH) is generally observed in the patients with the tallest H2 and the lowest BA2:CA2 ratio, due to the notable deterioration of height prognosis which frequently follows therapy interruption; 4) In order to strengthen the weak therapeutic effect of GnRH agonists in CTPP, this treatment should be discontinued at a BA of 12-12.5 years.     

Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone.

We evaluated height prognosis and therapeutic efficacy of long-term, combination therapy with gonadotropin releasing-hormone agonist and growth hormone (GH) in five children (three girls) with coexistent precocious puberty and GH deficiency. Their clinical characteristics and growth response were compared with those of 12 girls with idiopathic true precocious puberty and eight prepubertal GH-deficient children (one girl). Precocious GH-deficient subjects were older than the precocious GH-sufficient children (9.5 +/- 1.8 years vs 6.5 +/- 1.3 years; mean +/- SD), but bone ages were comparable (12 +/- 3.7 years vs 10 +/- 0.9 years); their chronologic age was similar to that of the prepubertal GH-deficient children (9.6 +/- 2.1 years), but bone age was significantly more advanced (6.9 +/- 2.3 years). The mean height velocity of the prepubertal GH-deficient children (3.8 +/- 1.5 cm/yr) was lower than that of the precocious GH-deficient subjects (6.7 +/- 1.6 cm/yr) and the precocious GH-sufficient children (9.5 +/- 2.9 cm/yr). Baseline adult height prediction z scores were significantly lower in the precocious GH-deficient children (-3.7 +/- 1.0) than in either the precocious GH-sufficient children (-2.2 +/- 1.0) or the prepubertal GH-deficient subjects (-1.5 +/- 0.8). During therapy with gonadotropin releasing-hormone agonist, growth rates slowed to an average of 3.7 cm/yr in the precocious GH-deficient children but increased after the addition of GH to 7.4 cm during the first year of combination therapy. After 2 to 3 years of combination therapy, height predictions increased an average of 10 cm, compared with an increase of 2.8 cm in the precocious GH-sufficient group treated with gonadotropin releasing-hormone agonist alone. We conclude that combination treatment with gonadotropin releasing-hormone agonist and GH improves the height prognosis of children with coexistent true precocious puberty and GH deficiency, but falls short of achieving normal adult height potential.     

The effect of growth hormone treatment on stature in Aarskog syndrome.

We describe 19 males with Aarskog syndrome who were treated with growth hormone (GH) and enrolled in the National Cooperative Growth Study (NCGS). There was a significant increase in both growth rate (3.9 +/- 1.9 cm/yr vs 8.9 +/- 1.7 cm/yr, p < 0.001) and height SD score (change in HtSDS = 1.0 +/- 0.8). The increase in HtSDS was dependent on treatment duration, frequency of injections, weight-for-height SDS, and HtSDS at enrollment. The results of our study suggest a positive effect of GH treatment on growth and adult height in Aarskog syndrome patients.     

Gonadotrophin-Releasing Hormone Agonist Treatment of Central Precocious Puberty: an Analysis of Growth Data in a Developmental Context

ABSTRACT. Growth and skeletal maturation was assessed in 83 girls with central precocious puberty (CPP) during pituitary—gonadal suppression induced by treatment with a gonadotrophin-releasing hormone agonist (GnRHa). The mean pretreatment chronological age (CA) was 6.3 years and the mean bone age (BA) was 10.6 years. During the suppression of gonadal sex steroid secretion, mean height velocity (HV) decreased from a pretreatment value of 10.8 cm/year to 5.9 (year 1, n = 83), 4.9 (year 2, n = 72), 4.2 (year 3, n = 49, and 4.4 (year 4, n = 23) cm/year. During each interval, there was a negative correlation between HV and the pretreatment BA. In addition, the rate of skeletal maturation was reduced during GnRHa treatment (ΔBA/ΔCA = 0.6 ± 0.1 over 3 years, n = 45). The rate of skeletal maturation during therapy was also negatively correlated with pretreatment BA. Predicted adult stature, based upon z -scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, ΔBA/ΔCA, and the change in height SDS for BA (ΔHT SDS for BA) during pituitary—gonadal suppression all correlated with the initial degree of skeletal maturation, the effect of GnRHa therapy on Final adult height in children with CPP will be best understood if growth data are assessed within a developmental framework.     

Effect of GnRH analogue on height potential in patients with severe growth hormone insensitivity syndrome treated with IGF-I

Children with growth hormone insensitivity syndrome (GHIS) who receive insulin-like growth factor 1 (IGF-1) treatment and enter puberty with inadequate height gain are unlikely to reach adult height within the normal range. Final height standard deviation score (SDS) in most treated children is < or = -5. Combining IGF-1 with gonadotrophin-releasing hormone analogue (GnRHa) therapy may help to improve their final height. Three patients on IGF-1 treatment, two with primary GHI and one with secondary GHI, were started on GnRHa therapy at the onset of puberty. Their ages ranged from 6.4 years to 12.9 years at the start of IGF-1 therapy (120 microg/kg twice daily by subcutaneous injection). Gains in height/bone age SDSs under GnRHa therapy ranged from 0 to 0.9. Growth velocity on GnRHa therapy ranged from 4 cm/year to 4.8 cm/year. Bone maturation (measured as change in bone age divided by change in chronological age, deltaBA/deltaCA) decreased after the start of GnRHa therapy. Predicted adult height (PAH) improved in two patients and was maintained in one. Bone mineral density showed gradual improvement from baseline. Treatment with GnRHa resulted in a gain in PAH. Final height results will provide the definite answer on the effectiveness of this combined treatment.     

Third-generation Aromatase Inhibitor Improved Adult Height in a Japanese Boy with Testotoxicosis

In this study, we report a Japanese boy with testotoxicosis due to a heterozygous mutation [p. A572V] in the LH/CGR gene, who was the first boy treated with a third-generation aromatase inhibitor (AI) and reached his adult height in Japan. He showed accelerated growth and rapid penile growth from 3 yr of age and was diagnosed as having testotoxicosis. Combined treatment with anastrozole and spironolactone was started when he was 7 yr old and 145.8 cm (+4.45 SD) tall, at which point his bone age (BA) was 13.5 yr. His predicted adult height (PAH) was estimated to be 158.3 cm. The combined treatment was continued until he was 13 yr old and 166.5 cm tall, with his BA being 15.5 yr. He reached his adult height of 166.9 cm at 15 yr of age. Combined treatment with anastrozole and spironolactone successfully decelerated BA advancement, prolonged pubertal period and improved adult height.     

Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty: the Dutch experience

Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for central precocious puberty were studied. In girls mean FH exceeded initial height prediction by 7.4 (5.7) cm (p < 0.001); FH was significantly lower than target height, but still in the genetic target range. When treatment started < 6 years of age, height gain was significantly higher than when started > 8 years of age. Bone age (BA) and chronological age (CA) at start of treatment, as well as BA advance at cessation of treatment, were the most important variables influencing height gain in multiple regression analysis. BA advance at start of treatment was most important in simple correlation. In girls, GnRHa treatment seems to restore FH into the target range. A younger age and advanced bone age at start of treatment are associated with more height gain from GnRHa treatment.     

Improved final height in Turner's syndrome following growth-promoting treatment at a single centre

AIMS: To examine the final height (FH) outcome of girls with Turner's syndrome (TS) treated at a single Scottish centre (Glasgow group), to compare it with an earlier national analysis (Scottish group) and to suggest reasons for any change. METHODS: Retrospective growth and treatment data for 29 Glasgow patients were compared with those of 26 Scottish patients. RESULTS: Age at GH start (mean +/- SD) was 10.1 +/- 2.6 vs 12.1 +/- 1.7 y (p < 0.01) in the Glasgow versus Scottish groups, with overall duration of treatment 6.2 +/- 2.4 vs 3.7 +/- 1.1 y (p < 0.001) and years of GH treatment before pubertal induction 2.7 +/- 2.8 vs 0.3 +/- 0.8 y (p < 0.001), respectively. Pubertal induction was at a similar age: 12.7 +/- 1.8 vs 12.8 +/- 1.8 y (ns). FH was 151.1 +/- 4.6 cm in the Glasgow group compared with 142.6 +/- 5.6 cm in the Scottish group (p < 0.001), with FH - projected adult height (PAH) 5.7 +/- 4.6 cm vs 0.6 +/- 3.6 cm (p < 0.001), respectively. Univariate analysis of the Glasgow group's FH - PAH with a number of growth and treatment variables identified no statistically significant relationships. CONCLUSION: This group's improved FH and FH - PAH, relative to an earlier sample, are attributed to the introduction of GH treatment from a younger age and for longer, overall and before pubertal induction. In addition, the authors believe that compliance with treatment has been enhanced by this single centre's dedicated Turner clinic and the efforts of its established "growth team". These data demonstrate that a favourable FH can be achieved using a safe and financially viable dose of GH, while inducing puberty at a "normal" age.     

Adult height in advanced puberty with or without gonadotropin hormone releasing hormone analog treatment

Advanced puberty is defined as the onset of puberty in girls at 8-10 years of age and in boys at 9-11 years. This study analyzes adult height in 57 children with advanced puberty to evaluate the results of treating children (9 girls and 8 boys) with gonadotropin hormone releasing hormone (GnRH) analog and the impact of advanced puberty on adult height in untreated children (31 girls and 9 boys). For treated girls, adult height predicted at the onset of treatment (151.9+/-1.7 cm) was similar to the final adult height (155.3+/-1.4 cm), but lower than target height (157.2+/-1.6 cm, p = 0.04). For untreated girls, adult height predicted at the initial evaluation (156.7+/-1 cm) was also similar to adult height (157+/-1 cm), but lower than the target height (157.6+/-1 cm, p = 0.03). The adult heights of both treated and untreated girls were similar to their target heights. For treated boys, adult height predicted at the onset of treatment (173.2+/-3.1 cm) was greater than the final adult height (164.1+/-2.1 cm, p = 0.01), which was lower than target height (170.4+/-1.2 cm, p = 0.01). For untreated boys, adult height predicted at the initial evaluation (170.8+/-2.7 cm) was similar to both the adult height (169.1+/-1.9 cm) and target height (170.2+/-1.2 cm). Height gains between the onset of puberty and adult height were similar in treated (29.9+/-2.3 cm in girls and 29.8+/-1.7 cm in boys) and untreated (28.6+/-1 and 33.1+/-2 cm) children. When expressed as SD, the adult height was significantly shorter than that at 4 years in treated girls (difference 1 SD, p = 0.03), in untreated girls (difference 0.9 SD, p = 0.0002) and in treated boys (difference 0.9 SD, p = 0.02), but it was similar to that in untreated boys. Adult height was below target height by >5 cm in seven girls (two of them treated) and five boys (four of them treated). In conclusion, treating advanced puberty did not change the adult height reached by girls, and was associated with reduced growth potential in boys. The adult heights of untreated children were similar to those predicted at the initial evaluation and to target heights, but in girls they were 1 SD lower than the height at 4 years. These data suggest that advanced puberty decreases the growth potential by about 5 cm, and that GnRH analog treatment does not prevent this.     

下丘脑-垂体-性腺轴抑制程度对中枢性性早熟女童成年预测身高的影响

目的 研究促性腺激素释放激素类似物(GnRHa)治疗过程中下丘脑-垂体-性腺轴(HPGA)抑制程度与中枢性性早熟(CPP)女童成年预测身高(PAH)的关系,以指导临床个体化调节GnRHa 治疗剂量。方法 收集75 例CPP 女童的临床资料,记录GnRHa 治疗的不同时间点身高、骨龄(BA)、子宫卵巢容积及LH、FSH 峰值、E2 水平,计算各时间点PAH,分析PAH 改善(ΔPAH=PAH-靶身高)的情况及其与HPGA 抑制的关系,并采用阈值效应分析寻找ΔPAH 的最佳HPGA 抑制范围。结果 GnRHa 治疗后PAH 较治疗初期有明显改善。ΔPAH 与ΔBA 呈负相关;治疗24 月时ΔPAH 与LH 呈负相关。将子宫容积控制在2.3~3.0 mL 之间,LH 控制在0.8 IU/L 以下,FSH 控制在2.4 IU/L 以下对延缓BA 的增长及改善PAH 有利。结论 GnRHa 治疗能改善CPP 女童的PAH。选择合适的GnRHa 治疗剂量,将子宫容积、LH、FSH 控制在一定范围内,有利于延缓BA 及改善PAH。