Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin^®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.     

Efficacy and Safety of Up to 8 Years of Long-term Growth Hormone Treatment in Short Children Born Small for Gestational Age in Japan: Analysis of the Subpopulation According to the Japanese Guideline

The efficacy and safety of 8 yr of GH treatment was assessed in 44 Japanese children with small for gestational age (SGA) short stature who met the criteria for GH treatment initiation (height SD score (SDS) <–2.5 SD) of the Japanese guidelines. Height SDS in subjects improved throughout the study period, and average height SDS improved from –3.5 to –1.6 and from –3.4 to –1.9 in the 0.033/0.067 mg and 0.067/0.067 mg groups, respectively, after 8 yr of GH treatment. Delta height SD was approximately +2 after 4 yr of treatment, and ∆ IGF-1 showed a significant positive correlation with ∆ height SD after both 1 and 2 yr (r = 0.415 and 0.488, respectively) of treatment. There was no correlation between the age at the start of treatment and age at onset of puberty, and the median age at the onset of puberty in the subjects was almost the same as that in healthy children. In conclusion, clinically significant improvements in the height SDS was confirmed in short children born SGA after 8 yr of GH treatment without any safety problems.     

When and how to combine growth hormone with a luteinizing hormone-releasing hormone analogue

The effect of combined treatment with growth hormone (GH) and a luteinizing hormone-releasing hormone (LHRH) analogue, or GH alone, on pubertal height gain was assessed in an uncontrolled study in 15 boys and 10 girls with GH deficiency (GHD). Seven boys and six girls were treated with GH alone (group 1), and eight boys and four girls were treated with a combination of GH and an LHRH analogue during puberty (group 2). Mean ages (+/- SD) at the start of GH treatment and at the onset of puberty were significantly lower in group 2 (8.0 +/- 3.3 years and 11.2 +/- 0.8 years, respectively, in boys, and 6.3 +/- 1.6 years and 10.8 +/- 0.7 years in girls) than in group 1 (12.8 +/- 1.9 years and 13.7 +/- 1.4 years in boys, and 11.2 +/- 1.0 years and 12.5 +/- 1.2 years in girls). Height at the onset of puberty was less in group 2 than in group 1, but the difference was significant only for the boys. Combination treatment was started at a mean age of 11.7 +/- 1.2 years in boys and 11.5 +/- 1.0 years in girls. The duration of the combination treatment was 5.1 +/- 1.5 years in boys and 2.3 +/- 0.7 years in girls. The duration of the period between the onset of puberty and the end of GH treatment was significantly longer in group 2 (6.8 +/- 1.2 years in boys and 5.5 +/- 1.0 years in girls) than in group 1 (4.3 +/- 1.6 years in boys and 3.6 +/- 1.4 years in girls). The pubertal height gain was also significantly greater in group 2 (36.7 +/- 6.5 cm in boys and 29.0 +/- 8.3 cm in girls) than in group 1 (21.9 +/- 4.1 cm in boys and 18.6 +/- 4.1 cm in girls). Final height was significantly greater in group 2 than in group 1 in boys. Although there was no significant difference in final height between groups in the girls, the change in height SDS from the start of GH treatment until final height was significantly greater in group 2 (2.7 +/- 1.6 in boys and 4.5 +/- 0.5 SD in girls) than in group 1 (1.0 +/- 0.8 in boys and 1.8 +/- 0.9 SD in girls), in both boys and girls. In conclusion, it appears that combination of an LHRH analogue and GH may increase the pubertal height gain and the final height of children with GHD. The improvement is attributed to the prolongation of the treatment period, permitting slow bone maturation, and to the maintenance of height velocity. This combination treatment appears to be more effective in boys than girls. To fully assess this therapeutic approach, prospective controlled studies are needed.     

Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS

Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after >4 y GH treatment (including >1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH.     

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.     

Patterns of growth and body proportions after total-body irradiation and hematopoietic stem cell transplantation during childhood

Patterns of growth and body proportions were studied in 75 children receiving total-body irradiation (TBI) and hematopoietic stem cell transplantation (SCT) before onset of puberty. Of the 19 patients receiving GH, only data obtained before onset of GH were included. Thirty-two patients reached final height (FH). Median change in height SD score (SDS) between SCT and FH was -1.7 in boys and -1.1 in girls. Peak height velocity (PHV) was decreased in the majority of the patients (median PHV 5.7 cm/y in boys and 5.3 cm/y in girls), even though it occurred at appropriate ages. Changes in body proportions were analyzed by linear mixed-effects models. Decrease in sitting height SDS did not differ between boys and girls. In boys, decrease in leg length SDS was of comparable magnitude, whereas, in girls, decrease in leg length was less pronounced, leading to a significant decrease in SDS for sitting height/height ratio in girls only. The sex-specific effects of several variables on height SDS were analyzed by linear mixed-effects modeling, showing a slightly faster decrease in younger children and a more pronounced decrease during puberty in boys compared with girls. We conclude that 1) younger children are more susceptible to growth retardation after TBI and SCT, 2) pubertal growth is more compromised in boys, and 3) leg growth is relatively less affected in girls, possibly due to a high incidence of gonadal failure in girls.     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

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 justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period. AIMS: To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset. METHODS: Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment). RESULTS: In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls. CONCLUSIONS: High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.     

Outcome of premature thelarche: relation to puberty and final height

BACKGROUND—There is a debate about the possible progression of idiopathic premature thelarche towards precocious or early puberty.
OBJECTIVE—To evaluate height and age at onset of puberty in a group of girls with a history of idiopathic premature thelarche.
STUDY DESIGN—The height and age at onset of puberty of 42 girls now over 10 years of age who were diagnosed with isolated premature thelarche before the age of 3 years were evaluated.
RESULTS—Menarche was reached before or at 11 years of age in 13.5% of this group of girls. This percentage of early menarche was higher than would be expected from historical controls in the general population, but was consistent with maternal age of menarche. The mean (SD) height of the girls (n = 15) who achieved adult height was 162.9 (6.3) cm, which was slightly higher than the mean (SD) relative midparental height (160.7 (6.7) cm).
CONCLUSIONS—Isolated premature thelarche with onset before 3 years of age progresses towards precocious puberty, although this was consistent with the maternal age of menarche. Furthermore, adult height was normal when compared with population norms in all patients.

     

Subnormal Growth During Puberty in Children Treated for Acute Lymphoblastic Leukemia

Growth was studied longitudinally in 19 children who were long-term survivors after acute lymphoblastic leukemia (ALL). Of the children, 13 were girls; 6 were boys. They had all undergone a 3-year cytostatic treatment period which included vincristine, adriamycin, asparaginase, methotrexate, purinethol, and prednisone. Prophylactic cerebral irradiation (20-24 Gy) had been given to all children; 4 of them had also been given irradiation to the spine (10 Gy). The pattern of growth was nearly identical in girls and boys. Growth in relation to the therapy was almost normal, whereas growth during puberty was subnormal and final height was 1.3 SD less than expected at onset of disease. The growth pattern was the same for children with cerebrospinal irradiation as for those with cerebral irradiation. In view of the present results and previous studies on growth hormone (GH) secretion after cerebral irradiation, we suggest that treatment with luteinizing hormone releasing hormone (LHRH) or GH could be considered at puberty for children who have been treated for ALL, including cerebral irradiation, and who have a poor prognosis for final height.     

Anabolic steroid and gonadotropin releasing hormone analog combined treatment increased pubertal height gain and adult height in two children who entered puberty with short stature

We studied the effect of gonadal suppression treatment in combination with anabolic steroid on pubertal height gain and adult height in two children who entered puberty with short stature. Patient 1 was a female with idiopathic short stature. She received combined treatment with an anabolic steroid (stanozolol) and a gonadotropin releasing hormone analog (leuprorelin acetate). Her pubertal height gain was 28.5 cm, which is greater than that in normal height girls (20-25 cm). Patient 2 was a male with Aarskog syndrome. Although his growth hormone (GH) secretion was normal, he received GH treatment. Since GH administration did not accelerate his growth, he received combined treatment with stanozolol and leuprorelin acetate. His pubertal height gain was 27.0 cm, which is greater than that observed in GH deficient boys treated with GH alone (21.9 cm). Combined treatment with stanozolol and leuprorelin acetate appears to be effective in increasing pubertal height gain and adult height in children who enter puberty with short stature.     

Constitutional delay of growth and puberty: from presentation to final height

This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP.     

Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency

In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD score (SDS) increased throughout the three-year GH treatment period. The overall mean height SDS increased from –3.5 at baseline to –2.5 after 3 yr of treatment. The mean change in height SDS during these 3 yr was 1.1. In addition, height assessment of SD score based on Down syndrome-specific growth data in the Japanese population revealed that the height SDS (Down syndrome) also increased across the 3-yr GH treatment period. The mean change in height SDS (Down syndrome) during these three years was 1.3. GH therapy was effective for Down syndrome short stature accompanied by GHD, and no new safety concerns were found in this study.     

M-mode echocardiographic evaluation of systolic function, LV volume and mass in children on growth hormone therapy

Since abnormal endogenous growth hormone (GH) secretion in adults is associated with cardiac dysfunction, it is important to ensure that GH therapy in children and adolescents does not cause similar effects. Forty-two growth hormone-deficient children (Group 1) (19 girls, 23 boys) were evaluated. Six girls and seven boys were prepubertal with a mean age of 6.65 yr (range 4.37-9.73 yr). Twenty-nine were pubertal (13 girls, 16 boys), mean age 13.57 yr (range 10.08-16.76 yr). The patients had been on long-term GH therapy for 34.97 +/- 18.78 months with an average weekly dose of 17.61 IU/m2/wk. The mean height SDS was -2.85 +/- 1.22 for boys and -2.5 +/- 0.64 for girls at the onset of therapy, and at the time of examination -1.8 +/- 1.32 for the boys and 1.87 +/- 0.94 for the girls. Thirty-four normal control subjects (Group 2) matched for age, sex and body size were also studied. Left ventricular volume (LV), mass and systolic function [shortening fraction (FS)] were evaluated by two-dimensional guided M-mode echocardiography. Blood pressure was also measured. No differences in blood pressure were observed between patients and controls. There was no correlation of GH dose and duration of therapy with LV measurements. No significant differences were found between Group 1 and Group 2. These observations suggest that long term administration of GH does not produce adverse cardiac effects in GH deficient children. Nevertheless, longer follow-up studies are still needed to confirm the safety of long-term rhGH treatment.     

Management of Growth Hormone Deficiency Through Puberty

ABSTRACT. As a model of the growth hormone (GH) dependence of growth in prepuberty and puberty, the growth of 182 children (93 boys, 89 girls) who survived in first remission for treatment of acute lymphoblastic leukaemia was examined. Chemotherapy regimens, including intrathecal methotrexate, were similar in all patients, but CNS treatment differed, in that one group received 2400 cGy cranial irradiation, while the other received 1800 cGy. There was a significant decrease in height SDS during prepuberty, which was equivalent in both sexes, whereas there was a much greater decrease in pubertal growth in girls than in boys. Girls treated with the lower dose regimen of cranial irradiation had their onset of pubertal maturation significantly advanced, to a mean of 9.9 years ( p < 0.001). Previous studies have indicated that the duration of puberty is shortened by GH treatment in patients with idiopathic multiple pituitary hormone deficiency or isolated GH deficiency (GHD). To determine whether an increase in the dose of GH administered during the adolescent growth spurt would improve final height, a prospective randomized trial was performed in 32 children (25 boys, 7 girls) with isolated GHD treated with a GH dose regimen of 15 IU/m²/week as daily s.c. injections. At the onset of the pubertal growth spurt, the patients were randomized either to an unchanged dose or to 30 IU/m²/week. There was no significant change in height velocity with the doubled dose of GH, but there was a trend in the advancement of pubertal maturation which was considered to be dose related. It is suggested that these findings are of relevance to the treatment of GHD in puberty, especially in girls with early or precocious puberty occurring as a consequence of low-dose cranial irradiation. It is concluded that optimum final heights may not be achieved in these patients without the therapeutic manipulation of the onset and/or duration of puberty.     

Final height in girls with Turner's syndrome treated with once or twice daily growth hormone injections

OBJECTIVES—To study final height in girls with Turner''s syndrome treated with once or twice daily injections of growth hormone (GH) in combination with low dose ethinyl oestradiol.
DESIGN—Until final height was reached, the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m²/day. Twice daily injections were given as one third in the morning and two thirds at bedtime. All girls concurrently received low dose oestradiol (0.05 µg ethinyl oestradiol/kg/day, increased to 0.10 µg/kg/day after 2.25years).
PATIENTS—Nineteen girls with Turner''s syndrome aged ⩾ 11 years (mean (SD) 13.6 (1.7) years).
MEASUREMENTS—To determine final height gain, we assessed the difference between the attained final height and the final height predictions at the start of treatment. These final height predictions were calculated using the Bayley-Pinneau (BP) prediction method, the modified projected adult height (mPAH), the modified index of potential height (mIPH_RUS), and the Turner''s specific prediction method (PTS_RUS).
RESULTS—The gain in final height (mean (SD)) was not significantly different between the once daily and the twice daily regimens (7.6(2.3) v 5.1 (3.2) cm). All girls exceeded their adult height prediction (range, 1.6-12.3 cm). Thirteen of the 19 girls had a final height gain > 5.0 cm. Mean (SD) attained final height was 155.5 (5.4) cm. A "younger bone age" at baseline and a higher increase in height standard deviation score for chronological age (Dutch-Swedish-Danish references) in the first year of GH treatment predicted a higher final height gain after GH treatment.
CONCLUSIONS—Division of the total daily GH dose (6 IU/m²/day) into two thirds in the evening and one third in the morning is not advantageous over the once daily GH regimen with respect to final height gain. Treatment with a GH dose of 6 IU/m²/day in combination with low dose oestrogens can result in a significant increase in adult height in girls with Turner''s syndrome, even if they start GH treatment at a relatively late age.

     

Growth response, pubertal growth and final height in Greek children with growth hormone (GH) deficiency on long-term GH therapy and factors affecting outcome

The growth data of 156 children (100 boys, 56 girls) with growth hormone deficiency (GHD), treated with human growth hormone (GH) for 5.7+/-3.7 years, from 1970-1997, were retrospectively analyzed to assess the efficacy of GH treatment and the factors involved. 62.2% of the studied population had idiopathic GHD (IGHD) and 35.2% had organic GHD (OGHD). At initiation of treatment, chronological age (CA) was 10.1+/-4.0 years in children with IGHD and 9.7+/-4.0 years in those with OGHD, while bone age (BA) was 7.0+/-3.7 and 7.7+/-3.2 years, respectively. The SDS of the growth velocity during the first year of therapy (GV1) was negatively related to CA at start of therapy (r = -0.53, p = 0.01). 109 children have reached final height (FH): 67 boys (FH = 165.3+/-6.3 cm) and 42 girls (FH = 153.9+/-5.4 cm). FH SDS was not significantly different from target height (TH) SDS. In the total group, FH SDS was positively related to height SDS for CA and BA at start of therapy (p = 0.01, p = 0.001, respectively), to TH SDS (r = 0.40, p = 0.001), and to GV1 (r = 0.33, p = 0.001). TH SDS was not different between the IGHD and OGHD groups (-1.02+/-0.8 vs. -0.94+/-6.9). The height gain at puberty did not differ between the groups with induced or spontaneous puberty in boys (23.7+/-8.6 vs. 25.4+/-6.9, not significant), while in girls it was higher in the group with spontaneous puberty (12.7+/-7.3 vs. 20.0+/-9.0, p = 0.008). The age and height at start of puberty was higher in girls and boys with induced puberty. In the total group, the FH SDS of children with induced puberty was higher in comparison with those with spontaneous puberty (-1.0+/-0.8 vs. -1.7+/-0.9, p = 0.001) and it was positively related to the height at start of puberty. When the two sexes were analyzed separately, the difference reached significance only in boys. In conclusion, children with GHD on GH treatment achieved a final height which was comparable to their genetic potential. The FH of children with OGHD was not different from those with IGHD. The age and height at start of puberty were the most significant determining factors for FH. Hence, a better FH might be expected by delaying or arresting puberty.     

Spontaneous growth in idiopathic short stature. European Study Group

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.     

Spontaneous growth in idiopathic short stature. European Study Group.

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.     

Long-Term Results with a Slow-Release Gonadotrophin-Releasing Hormone Agonist in Central Precocious Puberty

ABSTRACT. As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean ± SD) increased from 158.9 ± 6.8 to 164.9 ± 6.6 cm in girls (n = 14, p < 0.01), and from 174.4 ± 18.5 to 184.3 ± 17.1 cm in boys (n = 4, p < 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 ± 0.5 years, menses started 9.8 ± 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 ± 0.1 to 5.4 ± 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2–3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height. It is concluded that triptorelin therapy improves predicted adult height. In children with CPP and genetic short stature, with a markedly decreased height velocity during triptorelin therapy, concomitant administration of a GnRH agonist and GH may have advantages. Further extensive studies are required.