Height SDS For Bone Age Research Articles

Development and validation of a model for predicting the adult height of girls with idiopathic central precocious puberty.

A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. •Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. •This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study.

GROWTH HORMONE THERAPY;

Objective: To detect growth hormone deficiency in short stature children and to observe the response of growth hormonereplacement therapy in isolated GH deficient. Design: An interventional descriptive study. Place and Duration of Study: The study wascarried out in the Department of Pediatrics at Military Hospital Rawalpindi in collaboration with Armed Forces Institute of PathologyRawalpindi over a period of two years from Jan 2007 to Dec 2008. Patients and Methods: Thirty short children between three to fourteenyears of age having isolated growth hormone deficiency confirmed by laboratory investigation were included in the study prospectivelyand retrospectively. Growth hormone replacement therapy with recombinant GH was given to all children at the dose of 0.14iu/kg, sixdays a week subcutaneously. Each patient was assessed and evaluated after every three months. Results: The mean chronologic agewas 8.05 +/- 2.74 years with a height age of 4.02 years. The male to female ratio was 1.72:1. They were treated with recombinant GH in adose of 0.14iu/kg, six days a week, subcutaneously at evening. Response to GH was excellent and the mean growth speed had gone upfrom 2.53 +/- 0.87 cm per year before the treatment to 8.94 +/- 3.18 cm / year in the first twelve months of treatment and 6.8 +/- 1.6cm / year during the second year of treatment. During the first twenty four months of treatment, height standard deviation score increasedby 1.0 +/- 0.4 SD (p < 0.0001) The height velocity increased, the bone age / chronological age ratio and height SDS for chronologicalage decreased, while height SDS for bone age increased. There were no adverse reactions. Conclusion: Short stature with classic growthhormone deficiency is not uncommon. Early diagnosis and prompt treatment with growth hormone replacement has a very goodoutcome and the child attains a reasonable height.

Effects of gonadotropin-releasing hormone analogs on height in girls with idiopathic central precocious puberty

Objective The purpose of this study was to evaluate effects of gonadotropin-releasing hormone analogs (GnRHa) on improvement of predicted adult height (PAH) in girls with idiopathic central precocious puberty (ICPP) initiating treatment at age of eight years or over and analyze its related factors.Methods Forty-nine girls with ICPP aged eight years and over were treated with GnRHa for ( 17.4 ±5.6) months initiating at age of (9.3 ± 0.6) years during 2005 and 2008.They were followed-up every three to six months to evaluate its effects on growth velocity (GV), height standard deviation score for chronological age (HtSDS-CA), height SDS for bone age (HtSDS-BA), PAH, and so on, as well as their related factors.Results PAH increased after GnRHa treatment, from ( 157.7 ± 4.5) cm six months after treatment to ( 159.2 ±4.4) cm 12 months after treatment, and to ( 160.8 ±5.0) cm by the end of treatment from ( 155.5 ±5.1 ) cm at its initiation (P ＜0.01 ).There was significant difference in PAH by the end of treatment and target height (TH) [( 157.6 ±3.4) cm].HtSDS-BA increased since six months after GnRHa treatment, from ( -0.64 ±0.68) six months to ( -0.52 ±0.70) 12 months after it and ( -0.36 ±0.68)by the its end, all significantly different from ( - 0.94 ± 0.68 ) that at the initiation of treatment ( P ＜0.01 ).There was no significant difference in HtSDS-CA before and after treatment.GV decreased from the initiation (6.3 ± 1.3) cm/yr to (4.8 ± 1.5) cm/yr by the end of treatment ( P ＜ 0.01 ).No significant association between PAH and age of the initiation of treatment and between PAH and age by the end of treatment were found (P ＞ 0.05 ).But, PAH reversely correlated with bone age, and positively correlated with HtSDS-CA, HtSDS-BA, GV, TH and length of treatment ( P ＜ 0.01 ).Conclusions GnRHa can remarkably improves PAH in girl with ICPP.PAH mainly correlates with HtSDS-BA, TH and GV at the initiation and the end of treatment. Key words: Puberty, precocious; Body height; Gonadotropin-releasing hormone analogs

High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature

Background: Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3–9 cm, which may not...

Management and outcome of central precocious puberty

Management and outcome of central precocious puberty

Effect of treatment on growth in congenital adrenal hyperplasia.

In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect.

Growth hormone treatment of short children born small for gestational age: reappraisal of the rate of bone maturation over 2 years and metanalysis of height gain over 4 years

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.

Combined GH and LHRH analog treatment in short children.

It has been reported that the final height in short children is strongly related to the height at the onset of pubertal development, and pubertal height gain in GH-treated children is not exceed the gain in normal children. Therefore, it is now the consensus that insufficient height at the onset of puberty leads to short final height. We have already demonstrated that the final height in GH-deficient children with spontaneous puberty with gonadal suppression therapy by medroxyprogesterone or cyproterone acetate was significantly taller than GHD with spontaneous puberty without gonadal suppression therapy. In this study, we treated short boys who started puberty at height shorter than 130 cm with combined GH and LHRH analog. Final height was predicted by the height SD score for bone age. Although pubertal growth spurt was not recognized in short children on combination treatment, bone age maturation over 11.5 years decelerated significantly to the rate of one year in three or four years. Even during this slow bone maturation period, growth velocity remained at 4 cm/year due to GH treatment. Therefore, height SDS for bone age was improved in combination with the elongation of treatment period by the slow bone maturation. Some investigators recommend not to delay induction if puberty much beyond the normal age to avoid psychological problems and ennuchoid proportion in these children. When we explained to our Japanese patients the chance of increasing the final height with gonadal suppression treatment and the risk of delaying the pubertal development, almost all children preferred taller final height to pubertal development and they did not experience much psychological trouble. The differences in social and cultural circumstances do, however, influence patients' preferences.

Changes in serum levels of IGF-I and IGFBP-3 in children with chronic renal failure.

The significance of serum insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in uremia is still controversial. In this study we measured serum IGF-I by immunoradiometric assay (IRMA) and IGFBP-3 levels by specific radioimmunoassay (RIA) in 28 children (aged 3-16 years) with end-stage (n = 14, on hemodialysis) and pre-terminal renal failure (n = 14) and in 15 age-matched healthy children. Thyroid function of the patients was also investigated and GH-stimulation tests with L-Dopa and insulin were performed. Neither IGF-I nor IGFBP-3 levels significantly correlated with mean height SDS for bone age or for chronological age in either non dialysis patients or pubertal (n = 10) or prepubertal patients (n = 18). These data was consistent with the concept that growth in CRF was not related to abnormalities in serum IGF-I or IGFBP-3 levels.

Long‐term treatment with growth hormone in Noonan's syndrome

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of ‐2.1 (range ‐4.1 to ‐ 0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from ‐3.3(range ‐4.2 to ‐2.2)to ‐2.4(range ‐3.3 to ‐ 1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was ‐2.1) (range ‐3.1 to ‐ 1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from ‐1.8 (range ‐ 2.8 to ‐ 09) to ‐1.2 (range ‐ 1.6 to ‐0.6).

Long-term treatment with growth hormone in Noonan's syndrome.

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of -2.1 (range -4.1 to -0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from -3.3 (range -4.2 to -2.2) to -2.4 (range -3.3 to -1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was -2.1) (range -3.1 to -1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from -1.8 (range -2.8 to -0.9) to -1.2 (range -1.6 to -0.6).

EFFECT OF A LONG ACTING LHRH ANALOGUE AND GH ON THE SUPPRESSION OF SECONDARY SEXUAL DEVELOPMENT AND FINAL HEIGHT

LHRH analogue therapy has been estimated as useful for suppressing secondary sexual development in cases of precocious puberty and is expected to improve final height. We studied changes in the pituitary and gonadal functions after cessation of LHRHa in patients exhibiting precocious puberty. Furthermore, we studied the effects of a combination therapy of LHRHa and growth hormone in short patients.<Patients and method> Group A; Five girls who had been diagnosed as exhibiting precocious puberty and had been treated with LHRHa(TAP-144-SR) during a period of 1.5 to 3.4years, and who were no loonger being treated. Group B; Six girls and a boy who underwent pubertal development and exhibited acceleration of bone maturation during a GH supplement for GH deficiency or short stature without GHD, were treated with LHRHa. GH was injected subcutaneously 4-6 times a week at a dosage of 0.5-0.6U/kg/w. A and B; LHRHa, 30-60 μg/ml, was administered via a subcutaneous injection every 4 weeks. Changes in secondary sexual characteristics, height velocity, bone age, height SDS for bone age, serum estradiol, serum gonadotropins and IGF-1 were observed in all patients, and serum GH was measured in group A. Height velocity/ΔBA and ΔBA/ΔCA were calculated in group B.<Results> A; After cessation of LHRHa treatment, secondary sexual characteristics began to progress within 6 months, and E2 and peak LH were elevated to the pubertal level within one year. Improvement of height SDS for BA and increase of height velocity continued at least 6 months after the off-therapy. B; After LHRHa treatment, secondary sexual characteristics were attenuated, acceleration of bone maturation was suppressed and hormonal parameters decreased to the prepubertal range in all cases. Height SDS for BA, growth velocity/ΔBA and ΔBA/ΔCA were all improved by LHRHa treatment.<Conclusion> The suppression of pubertal bone maturation by LHRHa was significant. On the other hand, secondary sexual characteristics developed promptly after the cessation of LHRHa treatment. This data suggests the possibility of improving final height without any side effects by a combination therapy consisting of GH and LHRHa.

The long-term effect of cyproterone acetate on growth in girls with idiopathic precocious puberty. Androcur Study Group in Japan.

To define the effect of cyproterone acetate (CPA) on statural growth, 25 girls with idiopathic precocious puberty who had been treated with CPA were studied retrospectively. The final height SDS was -1.12 +/- 1.16 (mean +/- SD). The daily CPA dose was negatively related to the final height SDS. We divided our subjects into two groups according to the daily CPA dose [low dose, 84.9 +/- 15.4 mg/m2 (n = 19) vs high dose, 135.8 +/- 17.1 mg/m2 (n = 6)]. In the low dose group, the difference of the final height SDS minus height SDS for bone age at the initiation of CPA treatment was 0.55 +/- 1.16 and final height SDS was -0.82 +/- 1.05. The final height was not significantly different from the target height in the low dose group subjects whose target heights were obtained. Since the increment of height age to the increment of bone age during the treatment was significantly less in the group needing and treated with high dose CPA, high doses of CPA may reduce growth velocity more than its suppressive effect on bone maturation. These results suggest that CPA has an effect on statural growth in girls whose clinical symptoms can be controlled with a low dose of CPA, although they have not been compared with final height in untreated Japanese girls.

Gonadotropin Releasing Hormone Analogue and Growth Hormone Therapy in Precocious and Premature Puberty following Cranial Irradiation for Acute Lymphoblastic Leukaemia

Ten girls with early puberty secondary to cranial irradiation as a part of the treatment for acute lymphoblastic leukaemia (ALL) were treated with either gonadotropin-releasing hormone analogue (GnRHa) and human growth hormone (GH) (8 girls) or with GnRHa alone (2 girls). After 4 years of treatment, height SDS for bone age was improved in the group who received combined treatment (from -0.97 to +0.07, p < 0.001), in contrast to the 2 patients who received GnRHa alone in whom height standard deviation scores for bone age decreased (from -1.10 to -1.33). Sitting height in all patients was relatively shorter than leg length, and there was no significant alteration during the 4 years of treatment.

Treatment of Growth Hormone Deficient Patients with Recombinant Somatropin for 1 year: Results of a Chinese Multicentre Trial

Fifty-nine patients with idiopathic growth hormone deficiency were included in a Chinese multicentre trial of recombinant somatropin, 0.5-0.7 IU/kg/week s.c. given in six or seven divided doses. The height velocity increased from 2.8 +/- 1.0 cm/year to 13.1 +/- 2.5 cm/year during 1 year of treatment, and typical catch-up growth was observed. The increase in height SDS for chronological age was significant, but the increase in height SDS for bone age was not statistically significant. No adverse reactions to the treatment were recorded. Recombinant somatropin was shown to be very effective and safe during the first year of therapy in patients with growth hormone deficiency.

Precocious or early puberty and growth failure in girls treated for acute lymphoblastic leukaemia.

We have studied 41 children with early or precocious puberty who have been treated for acute lymphoblastic leukaemia with prophylactic cranial irradiation (1,800-2,400 cGy) accompanied by intrathecal methotrexate and systemic chemotherapy. Mean age at radiotherapy was 3.9 years (range 1.7-7.7) in the girls and 4.8 years (range 2.6-7.8) in the boys. Mean age at the onset of puberty was 8.6 years (range 6.7-9.7) in the girls and 9.3 years (range 7.8-10.3) in the boys. Of the 41 children with early puberty (greater than 1.4 SD from the mean) 36 were females and 5 were males. 21 of the 36 girls had an absent or inadequate growth acceleration of puberty. 7 of 12 girls who had a pharmacological test of growth hormone (GH) secretion had GH insufficiency (peak level less than 20 mU/l). Early or precocious puberty combined with GH insufficiency may produce severe growth failure and we have used a treatment regimen of a gonadotrophin-releasing hormone analogue, in order to reduce the rate of epiphyseal maturation, combined with biosynthetic GH to increase or sustain growth rate. We have treated 4 girls in this manner. During a mean treatment period of 0.86 years, height SDS for bone age rose from a mean of -1.06 to -0.59. Longer treatment periods will be required to assess the effect on final height.

The effect of cyproterone acetate on the growth of children with central precocious puberty.

We have examined the growth and skeletal maturation of 19 children (6 male, 13 female) with central precocious puberty. The aetiology in nine patients (5 male, 4 female) was secondary to a hypothalamic hamartoma. Six children (2 male, 4 female) received no treatment whereas 13 children (4 male, 9 female) were treated with cyproterone acetate in a mean dose of 68 mg/m2 per day (range, 34-260) for a mean duration of 4.5 years (range, 0.8-7.9). There was no significant difference between height SDS for bone age at the beginning and end of observation in either treated or untreated groups. No significant relationship between the mean dose of cyproterone acetate used and change in height SDS for bone age could be determined. We conclude that cyproterone acetate has no beneficial effect on the growth prognosis of children with central precocious puberty.