Randomised trial of LHRH analogue treatment on final height in girls with onset of puberty aged 7.5-8.5 years

OBJECTIVE—To study the effectiveness of luteinising hormone releasing hormone (LHRH) analogues in improving final height in girls affected by early puberty.PATIENTS—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).RESULTS—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.CONCLUSIONS—LHRH analogue has no apparent effect on final height in subjects with onset of puberty between 7.5 and 8.5years.     

Onset of puberty at eight years of age in girls determines a specific tempo of puberty but does not affect adult height

AIMS: To analyse the effect of early puberty (onset between 7.5 and 8.5 y) on pubertal growth and adult height in girls, and the implications of this effect for the age limit for normal onset of puberty. METHODS: Longitudinal study in Reus (Spain) of 32 girls with early puberty until they reached adult height. Data from these girls were compared with longitudinal data from girls (116) from the same population with normal onset at 10 (n = 37), 11 (n = 47), 12 (n = 19) and 13 (n = 13)y. We analysed height, target height, adult height, pubertal height increase, duration of pubertal growth, age at menarche and time to menarche. RESULTS: The adult height of girls with early puberty (160.9 +/- 5.4cm) was similar to that of girls with onset at later ages (p = not significant). In these girls, puberty lasted 5.4 +/- 0.7 y and the mean growth during puberty was 31.1 +/- 3.5 cm. As the age of onset of puberty increases, the duration of puberty and mean growth during puberty progressively decreased (p < 0.001). Girls with early puberty reached menarche at a mean age of 10.9 +/- 1.0 y, 3.2 +/- 0.9 y after onset of puberty, and this time span was greater than in the other groups. CONCLUSION: Girls with onset of puberty at 8 y show all the compensatory phenomena related to height at onset, pubertal duration and height increase during puberty. These phenomena cause their adult height to be similar to that of girls who begin puberty at the age of 10 to 13 y.     

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.     

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.     

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］     

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.

     

Growth prognosis and growth after menarche in primary hypothyroidism.

The long term growth of 20 girls and nine boys with juvenile primary hypothyroidism was studied until they reached final height. At diagnosis the girls had a mean age of 8.8 years (range 3.0-13.0); mean bone age was 5.4 years. The mean age of the boys at diagnosis was 9.5 years (range 3.7-14.2); mean bone age was 6.3 years. The patients were treated with thyroxine 100 micrograms/m2/day and serum thyroxine concentrations were maintained in the normal range. During treatment the rate of skeletal maturation exceeded the change in chronological age. Initial mean height SD score for bone age before treatment in the girls was +0.59 and after 11 years of treatment fell to -0.55 Mean height SD score for bone age in the boys decreased from +1.6 to -0.87 during treatment. In the girls the onset of puberty was 1.2 years later than the normal population but the duration of puberty was reduced. Mean age (SD) of menarche was 13.8 (1.7) years. The pattern of growth in girls with treated hypothyroidism was abnormal as growth continued after menarche, at a time when normal girls have almost stopped growing. During the second year after menarche our patients still had a mean growth velocity of 4.1 cm/year. Our data suggest that juvenile primary hypothyroidism results in a permanent height deficit. In addition, there is a loss of the normal harmony between growth and sexual maturation in girls, despite adequate treatment, in that growth continues for much longer after menarche than in normal girls.     

Preserving adult height potential in girls with idiopathic true precocious puberty

We designed a prospective study of height potential in girls with idiopathic precocious puberty, comparing the presenting features of girls with and without evidence of reduced adult height potential. The 14 girls with impaired adult height prognoses (group 1) were reexamined after treatment with a gonadotropin releasing hormone agonist, nafarelin. The seven girls with the prognosis of unimpaired height (group 2) were followed without therapy. We found that the group could be distinguished at initial examination by the greater bone age/height age ratio of group 1 (mean +/- SEM: 1.4 +/- 0.06 vs 1.0 +/- 0.05; p less than 0.005) and by the greater difference between predicted height and target height in group 1. The mean predicted height in group 1 was significantly less than the mean target height (150.7 +/- 2.1 vs 165.4 +/- 3.0 cm; p less than 0.005), whereas the mean predicted and target heights in group 2 were similar (165.4 +/- 3.0 vs 164.3 +/- 2.1 cm). Initial estradiol levels were also greater in group 1 than in group 2 (21.6 vs 10.6 pg/ml; p less than 0.05), although this difference was not sustained during follow-up. In group 1, nafarelin therapy suppressed the pituitary-gonadal axis, and although there was a transient reduction in height potential in girls with the youngest bone ages during the first 6 months of therapy, 2 years of treatment slightly improved predicted heights from 150.7 +/- 2.1 to 152.7 +/- 2.0 cm (p less than 0.05). Height predictions also increased without therapy during the 2-year observation period in group 2, from 165.4 +/- 3.0 to 168.7 +/- 4.1 cm (p less than 0.05). Our data indicate that gonadotropin releasing hormone agonist therapy preserves height potential in girls with an initially impaired height prognosis, and that height potential is preserved without therapy in those with a good initial height prognosis.     

Disturbed pubertal growth in girls treated for acute lymphoblastic leukemia

Pubertal growth was studied in 10 girls previously treated for acute lymphoblastic leukemia. The average age at menarche was 12.2 years, which is significantly lower (p less than 0.01) than the expected 13.1 years. Compared with normal girls, these girls showed a subnormal (p less than 0.05) peak height velocity during the second year before menarche. The remaining growth before menarche as well as the total postmenarchal growth was close to the normal average. The average final standing height was 1 SD less than what would be expected from their height 1 year after the cessation of therapy. A relative growth hormone deficiency in combination with early onset of puberty could account for this loss in final height.     

Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty

The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration >2 years, 3.1±0.3 years, mean ±SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152±1.8 cm before therapy to 162.2±1.2 cm (P<0.01) at the last evaluation performed 4.5±0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2±1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r=0.66,P<0.02), predicted final height at the onset of therapy (r=–0.76,P<0.001), and the difference between the target height and the predicted height at onset of therapy (r=0.76,P<0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis.This work was presented in part at the international symposium on GnRH analogues in cancer and human reproduction, Geneva, November 1990. Abstract, Gynecol Endocrinol 4 [Suppl 2]:101 (1990)     

Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment?

OBJECTIVE: To evaluate prospectively pubertal and predicted adult height progression until final height (FH) or near FH in girls with apparent idiopathic precocious puberty who were not treated. STUDY DESIGN: The decision not to treat at the time of initial evaluation was based on evidence of slowly progressive puberty as shown by bone age (BA) advancement <2 years above the chronologic age, whatever the hypothalamic pituitary ovarian axis activation, or no evidence of hypothalamic pituitary ovarian axis activation, whatever the BA advancement. During follow-up, patients who showed a significant decrease in predicted FH were treated with gonadotropin-releasing hormone agonist. RESULTS: Twenty-six girls with idiopathic precocious puberty were studied at a mean chronologic age of 7.4 +/- 0.9 years during a follow-up period of 6.6 +/- 2.2 years until FH or near FH. During the first 2 years of follow-up, most of the patients (group 1, n = 17; 65% of the cases) showed no substantial changes in predicted FH. They never required treatment, and menarche occurred at a mean chronologic age of 11.9 +/- 0.6 years. Their mean FH (or near FH) at 160.7 +/- 5.7 cm was close to their target height (161.3 +/- 4.7 cm). On the other hand, after a mean follow-up period of 1.4 +/- 0.8 years, 9 patients (group 2) had acceleration of bone maturation and deterioration of their predicted FH (from 162.1 +/- 6. 2 cm to 155.3 +/- 5.6 cm; P <.01), which was at that time significantly lower than their target height (P <.05) (mean target height = 159.8 +/- 4.6 cm). They received a gonadotropin-releasing hormone agonist for 2.1 +/- 0.7 years, resulting in a restoration of growth prognosis (mean FH or near FH = 160.2 +/- 6.7 cm). CONCLUSIONS: This study demonstrates that not all patients with apparent idiopathic precocious puberty require medical treatment, notably when there is no evidence of hypothalamo-pituitary ovarian activation or no significantly advanced BA to impair height potential. Most show a slowly progressing puberty. However, careful follow-up of these patients is necessary up to at least 9 years of age, because until then height prediction may deteriorate, necessitating gonadotropin-releasing hormone agonist treatment in one third of the cases.     

基于初潮时骨龄预测女童初潮后身高剩余生长潜力的横断面调查

背景 初潮是女童进入青春发育后期的重要标志,也是身高干预的最后一个机会窗口期,且初潮受多种因素影响、个体差异很大。正确认识和掌握女童初潮后的生长规律和特点,可为临床实践中不同初潮年龄女童的终身高评估和干预决策的制定提供参考依据。目的 通过分析女童初潮时年龄、骨龄和体格发育特征,探讨初潮后预测终身高(PAH)的临床评估方法。设计 横断面调查。方法 回顾性收集2008至2018年于首都儿科研究所附属儿童医院(我院)生长发育门诊就诊、有女童月经初潮时间、体格测量数据、骨龄X片的病例。排除初潮时间与就诊时间间隔≥3个月的病例、病历诊断中有明确的影响儿童生长发育的疾病、病历诊断中有明确病因引起的继发性中枢性性早熟或外周性性早熟和既往使用过生长激素或促性腺激素释放激素抑制剂药物的病例。按事先定义的方法计算实际年龄、骨龄、身高的标准差分值(HtSDS)、PAH和预测生长潜力、骨龄HtSDS(HtSDS_BA)和女童遗传身高,3名儿童保健科医生从纸质或电子病历中按照纳入和排除标准筛选病历、提取数据和判断,单人录入至Epidata数据库。以初潮年龄每1岁为段分组,以初潮时骨龄每0.5岁为段分组。主要结局指标 初潮骨龄、PAH和预测生长潜力。结果 ① 694例女童的初潮年龄8.5~13.2(10.7±1.1)岁,初潮时骨龄12.4~12.8(12.4±0.6)岁。②初潮年龄越小的女童,骨龄提前越多,HtSDS也越高。例如,8~岁组骨龄提前(3.8±0.5)岁,HtSDS为2.6±1.3;13~岁组骨龄落后(0.7±0.7)岁,HtSDS为-1.05±0.59。骨龄校正后不同初潮年龄组的平均HtSDS_BA为-1.17~-0.68,组间差异较小。③初潮后的预测生长潜力为(7.3±2.6)cm,生长潜力仅与初潮时的骨龄高度负相关(r=-0.960,P<0.001),骨龄从11.0~岁组到13.0~岁组,平均生长潜力从12.7 cm降至4.0 cm(F=1 194.393,P<0.001)。④本研究获得PAH计算公式[0.868×身高(cm)-3.754×骨龄(岁)+73.677],拟合优度R²=0.992,据此计算预期达到不同终身高的女童初潮时身高应达到的临界值。例如,女童初潮时骨龄为12岁,PAH达到150 cm则初潮时身高应＞139.8 cm,PAH达到160 cm初潮时身高应＞151.3 cm。结论 女童初潮时骨龄相对稳定,骨龄是反映身体成熟度和预测月经来潮的可靠指标,也是预测初潮后生长潜力的关键指标。     

Disturbed Pubertal Growth in Girls after Acute Leukaemia: a Relative Growth Hormone Insufficiency with Late Presentation

Long-term follow-up of growth and development after acute lymphoblastic leukaemia (ALL) in childhood has previously been limited to the prepubertal period. This study describes pubertal growth, final height and the spontaneous secretion of GH in girls treated for ALL, including CNS irradiation with 24 Gy. Ten girls, treated earlier for ALL, experienced the menarche at a mean age of 12.2 years. This is significantly earlier than the mean for Swedish girls. Prepubertal growth was near normal after the end of therapy for leukaemia. Mean final height was -1.7 SD, which is 1.5 SD less than at onset and 1.0 SD less than 1 year after the end of treatment. Thirteen other girls had a blunted spontaneous secretion of GH, several years after treatment for ALL: there was no increase in GH secretion during puberty. These results suggest that girls who have been treated for ALL, including CNS irradiation, have a relative GH insufficiency. This insufficiency becomes obvious only when the girls cannot respond to the increased need for GH during the pubertal spurt.     

Final height and body disproportion in thalassaemic boys and girls with spontaneous or induced puberty

The aim of the study was to evaluate whether sex hormone replacement therapy adversely affected final height and body disproportion in thalassaemic boys and girls. Thirty-six patients with spontaneous (SP) or induced puberty (IP) were studied in order to define the pattern of height growth through three observations: the first (A) at the age of 7-9; the second (B) at onset of spontaneous or induced puberty; and the third (C) when final height was reached. We examined 14 females with SP (f-SP) and 8 with IP (f-IP); 7 males with SP (m-SP) and 7 with IP (m-IP). Girls with IP reached the same final height of girls with SP (f-IP 153.8 (4.3) versus f-SP 154.4 (5.5) cm); p > 0.05) close to target height (f-IP 155.9 (5.2) cm versus f-SP 155.5 (3.6) cm). Girls with IP reached the final height at older chronological age (CA) (17.0 (0.6) y) than girls with SP (CA of 15.3 (0.7) y), but at the same bone age (BA) (f-IP 15.1 (0.9) y versus f-SP 14.8 (0.6) y). There was no difference between the two groups for pubertal growth (f-SP 16.2 (7.7) cm versus f-IP 12.2 (7.4) cm (p > 0.05)) that was negatively correlated with both prepubertal growth and BA at onset of puberty in both groups. Values of sitting height (sds) with respect to BA (SHsdsBA) were not significantly different between the two groups, and showed a worsening from the first observation to final height, reaching values around -2 SD, in both groups. Values of subischial leg length (sds) with respect to BA (SLLsdsBA) were in the normal range at both observations in all girls. High serum ferritin levels were observed in both groups (f-SP 3189 (2296) ng/ml and f-IP 3998 (2545) ng/ml; p > 0.05). Also boys with induced puberty reached the same final height of those with spontaneous one (m-IP 160.9 (5.5) cm versus m-SP 161.8 (2.4) cm; p > 0.05), but it was lower than target height in both groups (m-IP 168.1 (4.1) cm versus m-SP 169.6 (3.2) cm). Boys with IP reached final height at CA of 18.6 (1.1) y slightly older than boys with SP (CA 17.2 (0.9) y), but at the same BA (m-IP 15.9 (1.5) y versus m-SP 16.3 (0.8) y). Pubertal growth values were significantly different between boys with SP 18.9 (5.3) cm and those with IP 13.8 (4.9) cm (p < 0.05), but they were negatively correlated with prepubertal growth values in both groups (m-SP r = -0.91; p < 0.002 and m-IP r = -0.51; p < 0.05). SHsdsBA showed a worsening from the first observation to final height, reaching values around -3 SD in both groups, while SLLsdsBA were always in the normal range in all patients. Serum ferritin levels were higher in boys with IP (3400 (1179) ng/ml) than in those with SP (2020 (496) ng/ml). Conclusions: Our data showed that: (a) patients of both sexes with induced puberty reached the same final height of patients with spontaneous puberty; (b) all patients showed a body disproportion with truncal shortening and normal leg length that was more severe in boys of both groups at final height; (c) body disproportion was independent of pubertal or prepubertal period of greater height gain, suggesting that sexual steroids replacement therapy did not adversely affect either final height or body disproportion. Further studies, focused on the pathogenesis of the truncal shortening, are necessary in order to acquire more insight into the causes of this impairment.     

Growth and sexual maturation in children after kidney transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving daily or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during puberty. Height at transplantation was greater than 2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (greater than 4.8 cm/yr). Onset of puberty was recorded at a chronologic age of 14.6 +/- 1.9 years in boys and 13.3 +/- 1.9 years in girls. Height at onset of puberty related to chronologic age was -2.4 +/- 1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In girls, menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained an adult height greater than 2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great influence on adult height, the loss of growth potential during pubertal development seems even more important.     

Menarcheal age and growth pattern of Indian girls adopted in Sweden. II. Catch-up growth and final height

Adopted girls (n=107) previously studied regarding menarcheal age in relation to age at arrival, were analysed as to growth pattern and final height related to nutritional status at arrival and menarcheal age. It was found that most girls had catch-up growth regarding height and half of them regarding weight. Faster catch-up and later arrival age in Sweden were associated with earlier menarche. The catch-up growth was, however, incomplete, and lower the initial height for age, lower was the height for age at the succeeding measurements, and the final height. The mean final height was 154 cm, but 8% of the girls were 145 cm or shorter. The data suggest that linear growth and final height is influenced by the preadoptive nutritional condition, as well as by the degree and timing of subsequent catch-up growth, and the timing of puberty. Pubertal onset is related to the degree and timing of catch-up growth.     

Impaired pubertal growth in acute lymphoblastic leukaemia.

The growth of 182 patients who were long term survivors of childhood acute lymphoblastic leukaemia was retrospectively analysed. All remained in first remission and were treated with either 1800 or 2400 cGy of cranial irradiation. None had been treated with either testicular or spinal irradiation. Ninety three (51 boys, 42 girls) were treated with 2400 cGy and 89 (42 boys, 47 girls) were treated with 1800 cGy cranial irradiation. All patients were treated with standard chemotherapy including intrathecal methotrexate in similar dose regimens in either group. Mean age (SD) at diagnosis in the group treated with 2400 cGy was 4.8 (2.6) years and mean age in the group treated with 1800 cGy was 6.5 (3.3) years. Mean height SD score at diagnosis in the 2400 cGy group was +0.29 and final height achieved was -0.63. Mean height SD score at the start of treatment in the group treated with 1800 cGy was +0.40 and mean final height was -0.53. There was a similar reduction in height SD score in both groups during the pubertal growth spurt. The decrement in height SD score was greater when treatment was administered at less than 7 years of age in either dose regimen, both in prepubertal and pubertal growth. However, the decrease in height SD score was found to be greater in girls than boys. There was a trend in both sexes for the onset of puberty to be at a younger age with a lower treatment dose of radiotherapy. However, in girls treated with the lower dose regimen there was a significant reduction in the mean age of onset of puberty which was 9.9 years. Our data suggest that girls treated at less than 7 years of age have a severe impairment of pubertal growth, which is probably a combination of the dual endocrinopathy of premature puberty and growth hormone insufficiency.     

Constitutional delay of growth: expected versus final adult height

Constitutional delay of growth and puberty is believed to represent a variation of normal growth, and it is expected that children with this condition will grow for a longer duration than average and reach a height that is normal for their genetic potential. The records of children with constitutional delay of growth and puberty who were initially seen in the Pediatric Endocrine Clinic at the Oregon Health Sciences University between 1975 and 1983 were retrospectively reviewed. Criteria for study included a height more than 2 SD below the mean, a significantly delayed bone age, and a normal growth velocity on follow-up. Forty-two subjects were located and final adult height measurements were obtained. AT contact, the 29 male subjects (mean age = 23.9 years) were 169.5 +/- 4.5 cm tall (mean +/- SD), and the 13 female subjects (mean age = 20.5 years) were 156 +/- 3.8 cm tall. Adult height predictions during follow-up, using either the Bayley-Pinneau or Roche-Wainer-Thissen method, were close to final adult heights. The males were 1.2 SD and the females 1.3 SD below the 50th percentile as adults. This finding was not fully explained by genetic short stature; the males fell 5.1 cm and the females 5.3 cm below target heights based on midparental heights. It is concluded that this discrepancy is most likely explained by a selection bias of the shortest children referred to and observed in a subspecialty clinic, although a defect in human growth hormone secretion or function in children at the far end of the spectrum of constitutional delay of growth and puberty cannot be excluded.     

Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction

To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height.     

Response to Growth Hormone Treatment and Final Height after Cranial or Craniospinal Irradiation

ABSTRACT. Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children (61 boys and 39 girls) given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n=27) and the other with normal GH secretion (n= 17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n=10) and - 1.2 SD in the craniospinal (n = 18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4 SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age (10.6±0.3 yr in girls and 11.0± 0.3 yr in boys) and bone age (9.6 ± 0.4 yr in girls and 12.6 ± 0.3 in boys) than the idiopathic GHD patients. These data suggest that the results of hGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs.