trelstar and Growth-Disorders

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.. 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).. 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.. 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.

Topics: Body Height; Bone Development; Child; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Gonadotropins; Growth Disorders; Humans; Leuprolide; Puberty; Puberty, Precocious; Severity of Illness Index; Statistics, Nonparametric; Triptorelin Pamoate

Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist increases adult height in children with LHRH-dependent precocious puberty and is prescribed by some practitioners to augment height in short adolescents. We performed a randomized clinical trial to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty.. Fifty short adolescents (18 boys and 32 girls) with low predicted adult height (mean [+/-SD], 3.3+/-1.2 SD below the population mean) received either placebo (24 subjects) or an LHRH agonist (26 subjects). The mean (+/-SD) duration of treatment was 3.5+/-0.9 years in the LHRH-agonist group and 2.1+/-1.2 years in the placebo group (P<0.001). Adult height was measured when bone age exceeded 16 years in girls and 17 years in boys and when the rate of growth was less than 1.5 cm per year.. Forty-seven adolescents (94 percent) were followed until they attained adult height. At the time adult height was achieved, the subjects who had been treated with an LHRH agonist were older than those who had received placebo (20.5+/-2.1 years vs. 18.0+/-2.5 years, P=0.01) and were taller (standard-deviation score, -2.2+/-1.1 vs. -3.0+/-1.2; P=0.01). Analysis of covariance showed that LHRH-agonist treatment resulted in an increase of 0.6 (95 percent confidence interval, 0.2 to 0.9) in the standard-deviation score for height, or an increase of 4.2 cm (95 percent confidence interval, 1.7 to 6.7), over the initially predicted adult height (P=0.01). Treatment with an LHRH agonist resulted in significantly greater adult height than did placebo in boys and girls, in adolescents with idiopathic short stature, and in those who had a growth-limiting syndrome. The principal adverse event in the LHRH-agonist group was decreased accretion of bone mineral density (mean lumbar vertebral bone mineral density at the time adult height was achieved, 1.6+/-1.2 SD below the population mean, vs. 0.3+/-1.2 SD below the population mean in the placebo group; P<0.001).. Treatment with an LHRH agonist for 3.5 years increases adult height by 0.6 SD in adolescents with very short stature but substantially decreases bone mineral density. Such treatment cannot be routinely recommended to augment height in adolescents with normally timed puberty.

Topics: Adolescent; Body Height; Bone Density; Child; Double-Blind Method; Enzyme Inhibitors; Female; Follicle Stimulating Hormone; Growth; Growth Disorders; Humans; Luteinizing Hormone; Male; Puberty; Triptorelin Pamoate

To study the effectiveness of luteinising hormone releasing hormone (LHRH) analogues in improving final height in girls affected by early puberty.. Forty six consecutive girls with onset of puberty aged 7.5-8.5 years randomly divided into two groups: one treated with 3.75 mg triptorelin intramuscularly every four weeks (group 1); and the other with no treatment (group 2).. Mean (SD) chronological age at onset of menarche was significantly higher in group 1 than in group 2 (11.9 (1.0) v 10.8 (0.7) years). However, mean (SD) height at menarche (152.7 (7.2) v 152.5 (5.7) cm) and mean (SD) growth after menarche (4.9 (3.0) v 5.4 (2.2) cm) were similar in both groups. The mean (SD) final height was similar in the two groups (group 1, 158.1 (6.2) cm; group 2, 158. 6 (6.0) cm) and not significantly different from target height. Fourteen of 20 patients in group 1 and 12 of 18 patients in group 2 showed final height equal to or higher than target height. Final heights of girls with poor initial height prognosis were significantly lower than those of girls with good prognosis, but in patients with the same initial height prognosis, both groups showed final heights similar and not significantly different from their target heights.. LHRH analogue has no apparent effect on final height in subjects with onset of puberty between 7.5 and 8.5 years.

Topics: Analysis of Variance; Body Height; Child; Female; Follow-Up Studies; Growth Disorders; Humans; Injections, Intramuscular; Luteolytic Agents; Puberty, Precocious; Regression Analysis; Triptorelin Pamoate

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 +/- 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone Bn-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values stimulated levodopa GH peaks (pathological values (< 10.0 micrograms/l) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH-nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 +/- 0.9 cm/year; 6 months 6.4 +/- 1.9 cm/year, p < 0.001 versus baseline; 12 months 6.0 +/- 1.3 cm/year, p < 0.0001 versus baseline). There was a significant increase in height SDS for bone age (baseline -1.6 +/- 0.5 SDS; 12 months -1.04 +/- 0.6 SDS; p < 0.002) and in predicted adult height (baseline 152.0 +/- 3.6 cm; 12 months 155.9 +/- 3.4 cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.

Topics: Age Determination by Skeleton; Body Height; Child; Drug Therapy, Combination; Female; Growth; Growth Disorders; Growth Hormone; Humans; Insulin-Like Growth Factor I; Prognosis; Puberty, Precocious; Triptorelin Pamoate

We studied 30 girls (age 6.36 +/- 1.21 years, range 4.6-8.8) affected by idiopathic precocious puberty with significant reduction of height velocity (below the 25th centile) at the end of 1 year of Gn-RHa (triptorelin intramuscular depot) treatment, to evaluate GH-IGF-I axis activity and the effects of combined Gn-RHa plus hGH therapy. After 12 months, 15 patients continued Gn-RHa and started hGH therapy for 12 months, while 15 continued treatment with Gn-RHa alone (control group). We evaluated height velocity, bone age, urinary GH, serum IGF-I and IGFBP-3 levels throughout the study; plasma GHBP levels were determined only in the first 12 months of Gn-RHa treatment. Height velocity decreased significantly during Gn-RHa treatment; it increased significantly and became higher than the control group after 12 months of Gn-RHa plus hGH treatment. During Gn-RHa therapy alone, bone age progressed less than chronological age, while in the 12 months of Gn-RHa plus hGH treatment there was a slight nonsignificant increase in bone age progression in comparison to controls. Serum IGF-I and IGFBP-3 levels decreased significantly at 12 months of Gn-RHa therapy and increased significantly after Gn-RHa plus hGH treatment. Urinary GH levels showed the same behavior. Plasma GH binding to peak II-BP, slightly lower than the prepubertal normal range before treatment, significantly increased after 12 months of Gn-RHa treatment. Therefore, in these girls, during Gn-RHa treatment alone, we have a reduction in GH-IGF-I axis activity. During Gn-RHa plus hGH therapy there was a significant increase in height velocity, in urinary GH levels, in serum IGF-I and IGFBP-3 levels. Bone age did not seem to advance faster than chronological age and this may imply a better prediction in adult height. In our opinion, only in a small percentage of patients affected by precocious puberty (with a very low predicted adult height or an important reduction of growth velocity during Gn-RHa treatment) may an association with hGH therapy be useful.

Topics: Body Height; Child; Child, Preschool; Delayed-Action Preparations; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Hormone; Humans; Injections, Intramuscular; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Luteinizing Hormone; Luteolytic Agents; Puberty, Precocious; Recombinant Proteins; Triptorelin Pamoate

GH, 0.1 IU/kg/day 6 days/week, was given to 30 early pubertal short patients for 3 years. There were 16 males, aged 14.4 +/- 0.8 years, and 14 females, aged 12.2 +/- 1.2 years, at pubertal stage 2 or 3 with slow growth (4.2 +/- 1.2 cm/year) and no detected GH insufficiency or other cause for short stature. They were randomized in 2 groups: group A with GH alone, and group B with GH and a gonadotropin-releasing hormone agonist during the first 2 years. 28 of the 30 patients completed 3 years of treatment. The annual growth rate increased during the 1st year in both groups and sexes, the increase being significant (p < 0.01) in group A only. Patients of group A kept an improved growth velocity in the 2nd year, then returned to pretreatment growth rate in the 3rd year, while completing their sexual development and bone maturation. Their height, expressed as standard deviation score (SDS) for bone age, improved in the first 2 years, but decreased thereafter. Group B patients returned to pretreatment growth velocity in the 2nd year, and had no significant improvement in growth rate in the 3rd year with GH alone. Their bone maturation, slow when on the GnRH agonist, accelerated when sexual development resumed. At the end of the 3 years, height, expressed as SDS for age, improved in group A from -2.5 +/- 0.6 to -1.5 +/- 0.4 in males (p < 0.05) and from -2.8 +/- 0.5 to -2.1 +/- 0.9 in females (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Age Determination by Skeleton; Body Height; Child; Female; Growth; Growth Disorders; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Puberty; Testosterone; Time Factors; Triptorelin Pamoate

A group of 17 endocrinologically normal short stature adolescent (9 females aged 11.8 +/- 1.5 years and 8 males aged 13.2 +/- 1.1 years) referred at a pubertal stage II-III according to Tanner with a height prediction below -2.5 SD according to Bayley and Pinneau, were treated with long-acting D-Trp6-luteinizing hormone-releasing hormone (3.75 mg i.m. monthly for 24 months) and observed for a period of 13.4 +/- 5.8 months. Pubertal progression was suppressed during the 2 years of analogue therapy, then resumed shortly after the end of treatment. Annual growth rate remained in the prepubertal range during the treatment period and did not increase with the resumption of sexual development. A reduced rate of bone maturation was observed during the 2 years of analogue treatment without clear-cut improvement of the height to bone age relationship at the end of the treatment nor after the post-treatment observation period. Thus, after approximately 3 years of study, no significant improvement of predicted adult stature was obtained. There were no side-effects, but psychological problems mainly related to the failure to increase height. Though methods for predicting adult height are not accurate, these data suggest that use of luteinizing hormone-releasing hormone analogue in endocrinologically normal short subjects entering puberty at normal age with a poor height prognosis does not offer enough possible advantages on growth to offset the possible psychological drawbacks, and cannot be considered as routine treatment in this situation.

Topics: Adolescent; Age Determination by Skeleton; Body Height; Child; Delayed-Action Preparations; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Growth Disorders; Humans; Male; Prognosis; Puberty; Treatment Failure; Triptorelin Pamoate

The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function.. Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated).. FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02).. Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.

Topics: Adolescent; Adult; Child; Cohort Studies; Drug Combinations; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Growth Disorders; Human Growth Hormone; Humans; Luteolytic Agents; Puberty, Precocious; Time Factors; Treatment Outcome; Triptorelin Pamoate; Young Adult

Patients with GHRH receptor (GHRH-R) mutations present with familial isolated GH deficiency, which untreated leads to a severely compromised adult height. Few data are available about the efficacy of treatment with GH in combination with a GnRH analog (GnRHa) in adolescence.. The objective of the study was to describe the evolution of growth and skeletal age of a brother and sister of Moroccan descent with a homozygous GHRH-R mutation who presented at an advanced age (16 and 14.9 yr, respectively) and pubertal stage (Tanner stage G4 and B3, respectively) with a height of -5.1 sd score and -7.3 sd score on treatment with a combination of GH and GnRHa for 2.5 and 3 yr followed by GH alone.. GH was given in a dosage of 0.7 mg/m2.d (25 microg/kg.d) sc and triptorelin in a dosage of 3.75 mg per 4 wk im. Height and pubertal stage were measured three-monthly, bone age yearly.. Combined GH and GnRHa treatment resulted in a height gain of 24 and 28.2 cm, respectively, compared with the initial predicted adult height by the method of Bayley and Pinneau. Adult height was within the population range and well within the target range.. Our patients demonstrate that, in case of isolated GH deficiency caused by a GHRH-R mutation, combined treatment of GH and GnRHa can be very effective in increasing final height, even at an advanced bone age and pubertal stage.

Topics: Adult; Body Height; Female; Growth Disorders; Human Growth Hormone; Humans; Male; Morocco; Netherlands; Point Mutation; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Triptorelin Pamoate

Combined therapy with gonadotropin-releasing hormone (GnRH) analogue and growth hormone (GH) has been used to increase the height of adolescents who are not GH deficient and who have normally timed puberty. Its use, however, is still controversial. For 2 years simultaneously, we treated eight healthy girls with very low predicted adult height (PAH < 145 cm) who were entering into normally timed puberty. The GnRH analogue triptorelin pamoate (Decapeptyl, 100 microg/kg intramuscularly every 4 weeks) and GH (0.1 IU/kg/day subcutaneously, 6 days/week) were administered. The mean chronologic age (CA) of our patients was 11.01 +/- 0.95 years, and mean bone age (BA) was 12.25 +/- 1.13 years. With a height of 131.50 +/- 5.83 cm (-2.37 +/- 0.35 SD below the mean) and PAH of 140.87 +/- 3.53 cm, they were all in Tanner stage 2-3 of puberty (except one patient in stage 4). In all cases, GH and thyroid hormone deficiency were ruled out before the study began. Height and BA were measured immediately after discontinuation of therapy. PAH was determined before and at the end of therapy. Combined treatment resulted in a 4.13 +/- 1.19 cm increase in PAH (p < 0.01). Height increased significantly to 142.66 +/- 3.54 cm at the end of treatment (p < 0.01). Height standard deviation score for CA increased from -2.37 +/- 0.35 to -2.32 +/- 0.67, showing no significant improvement (p = 0.5). Height age (HA)/BA ratio and BA/CA ratio both demonstrated significant growth during the treatment (p < 0.03 and p < 0.01, respectively), whereas HA/CA ratio did not improve significantly (p < 0.32). During treatment, puberty was completely suppressed in all cases. Combination therapy with GnRH analogue and GH resulted in significant improvement in height and PAH during therapy. Additional, and perhaps more long-term, studies are required to show whether this kind of treatment is effective in improving final adult height. The cost-benefit of such therapies should also be taken into account.

Topics: Body Height; Child; Drug Therapy, Combination; Female; Growth Disorders; Growth Hormone; Humans; Triptorelin Pamoate

In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.

Topics: Age Determination by Skeleton; Body Height; Child; Child, Preschool; Estrogens; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Plate; Humans; Puberty; Puberty, Precocious; Regression Analysis; Time Factors; Triptorelin Pamoate

Topics: Adolescent; Body Height; Bone Density; Child; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Growth Disorders; Humans; Puberty; Triptorelin Pamoate

Topics: Adolescent; Bone Density; Growth Disorders; Humans; Triptorelin Pamoate

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean age at start 7.4 years) and group B (n=11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2-L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above -1 in both groups (group A: BUA Z-score -0.21, SOS Z-score -0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score -0.93, SOS Z-score -0.40, BMD Z-score -0.86, BMDvol Z-score -0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero (P=0.03 and P=0.02 respectively). Mean Z-score BMDvol was not significantly different from zero (P=0.05), we found no significant difference between the groups for BMDvol (P=0.13).. Although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.

Topics: Absorptiometry, Photon; Adolescent; Body Height; Bone Density; Calcaneus; Child; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Growth Disorders; Humans; Probability; Prospective Studies; Puberty, Precocious; Risk Assessment; Sensitivity and Specificity; Treatment Outcome; Triptorelin Pamoate; Ultrasonography, Doppler