Effect of Oxandrolone on Growth and Final Height in Turner's Syndrome

ABSTRACT. Thirty-two girls with Turner's syndrome aged 11.5-16.7 years were treated with oxandrolone (0.125 mg/kg/day). The treatment period was scheduled to 2 years. Height velocity (HV) was expressed in Standard Deviation Scores (SDS), calculated by growth standards for untreated Danish Turner-girls. For girls with initial bone age below 13 years HV increased significantly from a mean pretreatment value of -0.2 SDS (3.1 cm/year) to + 3.5 SDS (5.6 cm/year) in the 1st year of treatment and + 2.1 SDS (4.1 cm/year) in the 2nd year. Mean bone age velocity during treatment was 0.9 year/year. Twenty-two girls have reached final height. Predictions of their final height were made by three different methods and compared to observed final height. A significant ( p <0.001) improvement in the order of 3-4 cm was found for girls with initial bone age below 13 years, while girls with higher initial bone age had no height gain ( p >0.3). Side effects were seen in 16% of the girls.     

Oxandrolone in Girls with Turner's Syndrome

Twenty-six one-year treatment periods on oxandrolone (0.1 mg/kg/day) were studied in 20 patients with Turner's syndrome. Control patients with Turner's syndrome were matched by using the following criteria: difference in bone age being not greater than 0.S years and difference in the Bayley-Pinneau height prediction not greater than 3 cm. Height and height velocity were compared with standards of girls with Turner's syndrome (10) and expressed in standard deviation scores (SDS). On oxandrolone height velocity increased significantly from −0.3 SDS to +3.0 SDS. The increase in height velocity was negatively correlated to the bone age at onset of treatment ( r = 0.62, p<0.01). Height SDS improved by 0.45 SDS in the treated patients whereas it did not change in the control patients. The bone age velocity during the treatment period (including a six-month period after treatment) was 0.75 year/year in the treated, compared to 0.66 year/year in the control patients (NS). 15 of the 20 patients have reached final height. The difference in final height minus predicted height (Bayley-Pinneau) at onset of treatment was taken as a measure of "gain in final height". Seven of those (mean bone age 12.1 years at onset of treatment) were treated for one year only and had–compared to the matched controls–a mean net gain in final height of 2.5 cm (NS). Eight patients (mean bone age 10.1 years at onset of treatment) were treated for two one-year periods and had a significant mean net gain in final height of 5.2 cm. Height predictions calculated by the method of Lenko (14) gave an identical mean net gain in final height (5.1 cm)     

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

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

Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study

Demographic and auxological data were analysed from 818 girls with Turner's syndrome treated with recombinant human growth hormone (GH) and entered into the Kabi Pharmacia International Growth Study. Size at birth was low and correlated with the heights of both parents. The median age at start of GH treatment was 11.4 years and the parents had a median height SDS of -2.9. Height SDS at the start of treatment correlated with parental heights. Height velocities conformed to Turner-specific standards. The weight-for-height index increased sharply above 9 years of age. The frequency of spontaneous appearance of Tanner breast stage 2 was high (34.1% of girls > 10 years of age). Bone age (Greulich and Pyle) data were described by the equation: bone age = 1.61 (chronological age) -0.04(chronological age)² - 3.61. This equation was used to correct adult height predictions. The median initial dose of GH was 0.8 IUkglweek and was maintained during the first 3 years of treatment. The median frequency of injections was six/week. Height velocity increased from 4.1 to 6.8 cm/year in the first year, and height velocity SDS for chronological age remained positive for 4 years. The height prediction corrected for bone age increased over the first 2 years only. Differences in demography and auxology were described according to karyotype and country of origin. A greater height velocity SDS was observed at higher GH doses and when oxandrolone was used concomitantly.     

Changes with growth hormone treatment in growth hormone deficient children

A total of 54 previously untreated patients (15 girls, 39 boys) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated with human growth hormone (hGH), continuously up to 4 years. All of the patients had a peak hGH level which was below 10 ng/mL after at least two pharmacological tests and/or blunted physiologic hGH secretion, and their height was below ?2.5 s.d. for age and gender. After the 1st year of therapy, height velocity (HV) increased significantly when compared with baseline (from 3.18 ±0.76 cm/year to 9.17±1.03 cm/year; P <0.001), declined during the 2nd year and then remained significantly higher than pretreatment HV. When considering improvement in height expressed by height standard deviation score (SDS), during the therapy all of the patients showed a significant gain ± 1.72±1.09 (from ?4.11±0.61 to ?2.21±0.48). The height values were significantly higher than pretreatment, but remained below ?2 s.d. after 4 years of hGH therapy in our patients. Increased height velocity has been sustained, but height improvement after therapy was inversely correlated to height SDS for chronological age of patients at the start of therapy. In conclusion post-treatment height has been shown to be related to height deficit at the beginning of therapy. Therapy was well tolerated with no local or systemic adverse effects or acceleration of bone age.     

TREATMENT OF GIRLS WITH EXCESSIVE HEIGHT PREDICTION: Follow-up of Forty Girls Treated with Intramuscular Estradiol and Progesterone

Abstract. Andersen, H., Brock Jacobsen, B., Kastrup, K. W., Krabbe, S., Peitersen, B., Petersen, K. E., Thamdrup, E. and Wichmann, R. (Endocrine Clinic, Children's Hospital Fuglebakken, University of Copenhagen). Treatment of girls with excessive height prediction. Follow-up of 40 girls treated with intramuscular estradiol and progesterone. Acta Pædiatr Scand, 69:293, 1980.—In a follow-up study of 40 tall girls treated with intramuscular estradiol and progesterone, the final height, bone age maturation, side effects and acceptance of treatment were evaluated. The mean duration of treatment was 18 months. During treatment, mean height increase was 6.5 cm (height velocity 3.7 cm/year), which is nearly 50 % reduction of normal growth rate. The mean increase in bone age was 2.7 years (bone age velocity 1.8 years/year), which approximates twice the normal maturation rate. The mean reduction in final height was 5.0 cm as evaluated by the method of Bayley-Pinneau (BP), 2.9 cm by the method of Tanner et al. (TW) and 3.0 cm by the method of Roche et al. (RWT). The reduction was greatest when treatment was started before menarche, according to all three prediction methods. When treatment was started after menarche the calculated height reduction was greatest according to the BP method. There was good agreement between the three prediction methods in girls with a bone age below 12 years before treatment. In girls with a bone age above 12 years the height reduction by the BP method was much greater than when measured by the other methods. Side effects evaluated at follow-up were minimal and first menstruation occurred within 3 months (mean) after cessation of treatment. The number of pregnancies was estimated to be normal for age. All but three accepted the treatment. It is concluded that this type of treatment must be restricted to girls with severe psychological problems due to excessive height prognosis and selection for treatment must be based on an individualized evaluation.     

Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation?

Twenty four children (five girls, 19 boys) who had intrauterine growth retardation were treated with daily subcutaneous biosynthetic human growth hormone, initially in a dose of either 15 or 30 U/m2/week for the first year and in the latter dose for the next two years. Six patients (one girl, five boys) had no dysmorphic signs and 18 (four girls, 14 boys) had signs of Russel-Silver syndrome. All had birth weights below the third centile when adjusted for gestation age and all the children were below the third height centile at the start of treatment. Mean age was 6.3 years (range 2.1-9.7) when growth hormone treatment was started. All had normal growth hormone secretion to either a pharmacological or physiological test. In the first year of treatment, height velocity SD score increased from -0.75 to +3.6 in the group treated with 30 U/m2/week, and from -0.77 to +1.4 in the lower dose group. After three years of treatment, mean height velocity SD score was +1.1, irrespective of which initial treatment dose had been administered during the first year. There was no difference in the growth response of children with or without dysmorphic features. However, despite the sustained increase in growth rate, there was no significant change in height for bone age SD score, pointing to an unaltered final height outcome.     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

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 (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 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 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; 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.     

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis.

BACKGROUND: Turner syndrome accounts for 15-20% of childhood usage of growth hormone (GH) in the UK but final height benefit remains uncertain. The most effective strategy for oestrogen replacement is also unclear. METHODS: Fifty eight girls who, at start of treatment, were of mean age 9.1 years and projected final height 142.2 cm were randomised to receive in year 1, either low dose ethinyloestradiol 50-75 ng/kg/day, GH 28 IU/m(2) surface area/week as a daily injection, or a combination of ethinyloestradiol and GH. After the first year, the ethinyloestradiol treated girls received combination treatment. After two years, girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development. RESULTS: Near final height was available for 49 girls at age 16.5 years, 146.8 cm, representing a gain of 4.6 cm, range -7.9 to +11.7 cm. Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years. Height gain was correlated with greater initial height deficit. Fifteen girls (31%) reached 150 cm or more compared to a predicted 10%. Early supplementation with ethinyloestradiol provided no final height advantage. CONCLUSIONS: Final height gain was modest at 4.6 cm. Younger, shorter girls gained greatest height advantage from GH. Low dosage ethinyloestradiol before planned induction of puberty was not beneficial.     

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.     

Reduction of body height in tall girls by estrogen treatment]

Twenty-six girls with constitutional tall stature were treated with 0.5 mg ethinyloestradiol daily po and 10 mg norethisteronacetate from day 21 to 25 of the cycle for 1.4 +/- 0.4 years. Height, weight, bone age according to Greulich-Pyle (GP) and Tanner (RUS), height predictions according to Bayley Pinneau (BP) and Tanner Whitehouse (TW) were recorded at the onset of therapy, at the end of treatment and 7.4 years later. The mean chronological age at start of treatment was 12.6 +/- 1.1 years, bone age (GP) 12.4 +/- 0.7 years, (RUS) 13.5 +/- 0.7 years. The initial height prediction according to BP was 186.2 +/- 4.1 cm, which was 3.5 cm higher than the prognosis according to Tanner Whitehouse. Depending on the method used for height prediction, the height reduction by treatment was 4.6 +/- 3.0 cm (BP) or 1.4 +/- 2.2 cm (TW), respectively. The reduction of predicted height was more pronounced in girls with a bone age (GP) < 12.5 years at the initiation of therapy (n = 13), than in girls with a bone age > or = 12.5 years (n = 13). Final height was measured 7.4 years after the end of treatment. Chronological age: 21.3 +/- 3.7 years, final height 181.8 +/- 3.7 cm. Mean final height after therapy was 7.7 cm above target height, or, after allowance for the secular trend, 3.8 cm above target height. Body weight, recorded in centiles of body mass index, increased from the 38.5 +/- 26 to the 58.1 +/- 22 centile, weight gain was more pronounced in younger girls. At follow up investigation 18/19 girls, who answered a questionnaire, had a positive view of the previous treatment.     

Cerebral gigantism (Sotos syndrome). Compiled data of 22 cases

An in depth study on growth, bone age, cranial CT scans and plasma somatomedin activity (SM-act) was made of 22 children with Sotos syndrome. In addition to the known characteristics of the syndrome, thin and brittle nails were found in three adolescent patients. The mean body stature, expressed as standard deviation score, increased from 2.2–2.8 in the 1st year of life, followed by a fall to 2.0 in the 2nd year. Thereafter the SDS increased slowly to values of 3.0 at 10 years of age. At least two subjects have reached an exceptionally tall final stature. After the age of 2 years, SDS/year remained very stable (–0.1–0.2), concurring with growth velocities in the upper normal range. Bone age was advanced in all patients. Cranial CT scans showed ventricular widening, mid-line cava and Sylvian anomalies in nine, six, and three patients respectively. SM-act dropped from high or normal values in the 1st year, to below normal from 1–5 years, and returned thereafter to the lower half of normal or below the normal range.Abbreviations SM-act somatomedin activity - SM plasma somatomedin - SDS standard deviation score - CT computer tomography - HV SDS_CA height velocity standard deviation score for chronological age - HV SDS_BA height velocity standard deviation score for bone age     

Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age.

STUDY OBJECTIVE--To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome. DESIGN--Randomized study. SETTING--Referral-based pediatric endocrinology departments of seven university medical centers. PATIENTS--Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis. TREATMENT--Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen. RESULTS--The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects. CONCLUSIONS--Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

Growth hormone therapy in Silver Russell Syndrome: 5 years experience of the Australian and New Zealand Growth database (OZGROW)

Data were analysed on 33 children (22 males) with Silver Russell syndrome treated with growth hormone for periods up to 5 years. Baseline data (medians) at commencement of growth hormone (GH) therapy were age 6.7 years, bone age delay 1.7 years, height standard deviation score (SDS)-3.2, weight SDS –3.1, and growth velocity 5.7 cm/ year. All were prepubertal. Median birth weight SDS for gestational age was –3.2. GH was commenced at 14 IU/m² per week and subsequently adjusted according to response. Growth velocity and growth velocity SDS for chronological age (CA) improved over baseline and gains in height SDS for CA were 1.0, 1.5 and 1.8 SD over 3, 4 and 5 years respectively (P < 0.001). No significant increase in height SDS for bone age was observed. Increased GH doses were required after the 1st year to maintain growth rates. Mean bone age advancement was 3.1 years after 3 years of treatment, and 6.0 years after 5 years treatment. Younger age was a predictor of the growth response over the 1st year. Predictors of response after 3 years were catch-up growth, low weight SDS at birth and low height SDS for CA. Age at onset of puberty was normal, but height at onset of puberty was lower than normal means. Conclusion We have demonstrated significant improvement in growth in Silver Russell syndrome after 3 years of GH therapy, however data on estimated mature height and final height are insufficient to conclude final outcomes. Further follow up is required to assess the long-term benefit. Received: 19 July 1995 Accepted: 4 March 1996     

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis

BACKGROUND—Turner syndrome accounts for 15-20% of childhood usage of growth hormone (GH) in the UK but final height benefit remains uncertain. The most effective strategy for oestrogen replacement is also unclear.METHODS—Fifty eight girls who, at start of treatment, were of mean age 9.1 years and projected final height 142.2 cm were randomised to receive in year 1, either low dose ethinyloestradiol 50-75 ng/kg/day, GH 28 IU/m² surface area/week as a daily injection, or a combination of ethinyloestradiol and GH. After the first year, the ethinyloestradiol treated girls received combination treatment. After two years, girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development.RESULTS—Near final height was available for 49 girls at age 16.5 years, 146.8 cm, representing a gain of 4.6 cm, range ?7.9 to +11.7 cm. Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years. Height gain was correlated with greater initial height deficit. Fifteen girls (31%) reached 150 cm or more compared to a predicted 10%. Early supplementation with ethinyloestradiol provided no final height advantage.CONCLUSIONS—Final height gain was modest at 4.6 cm. Younger, shorter girls gained greatest height advantage from GH. Low dosage ethinyloestradiol before planned induction of puberty was not beneficial.     

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.     

Standards for growth and final height in Turner's syndrome

Data on birth, growth and final height were collected retrospectively for 78 women with Turner's syndrome born 1955-66. Seventy-one had received estrogen treatment from a mean age of 17.7 years (SD = 2.0 years), while 7 were spontaneously menstruating. At birth Turner girls were 440 g lighter (p less than 0.001) and 1.4 cm shorter (p less than 0.001) than 46,XX girls. Standards for untreated growth were established for the age period 6.5-17.5 years, while growth after 17.5 years was described in both untreated and estrogen treated women. Analysis of growth pattern showed that though no pubertal growth spurt was present, the steady decrease of height velocity (HV) was interrupted at the age of 9 years. HV was then constant until 12 years of age, whereafter it slowly decreased. Mean final height (FH) was 146.8 cm (SD = 5.8 cm, n = 76) compared to 166.8 cm in the general female population. No difference was found between 45,X women and women with other karyotypes (p greater than 0.7). Correlations between FH and parental heights, birthweight and birthlength were similar to those reported for normal women (19). FH varied with age at diagnosis. Those diagnosed after 17 years of age had a mean FH = 151.3 cm, while those diagnosed before had a mean FH = 145.8 cm (p less than 0.001).     

Effects of 5 years growth hormone treatment in patients with Prader-Willi syndrome

BACKGROUND: Short-term studies showed favorable effects of growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS). AIMS: To evaluate the long-term effects of GH therapy in patients with PWS retrospectively. PATIENTS AND METHODS: Effects of GH treatment (0.5 IU/kg/w s.c.) for a period of 1 to 5 years were assessed for 37 Japanese patients with PWS aged 3-(9/12) to 21-(3/12) years. Height and weight were expressed as standard deviation scores (SDSs) of Japanese PWS patients. Height velocity, final height, body mass index (BMI) and Rohrer index were also evaluated. RESULTS: After 1 year of treatment, the mean height velocity improved significantly from 4.32 to 8.69 cm per year (p < 00001). After 5 years of treatment, mean height SDS increased from -0.99 to +0.88 (p = 0.003). Mean final height of treated patients was 158.0 cm in males and 147.7 cm in females. Mean Rohrer index improved from 182 to 164 (p < 0.0001) after 1 year of treatment and stayed stable thereafter. CONCLUSIONS: Long-term treatment with GH in patients with PWS improved height velocity, height SDS, final height, and the degree of obesity. These data encourage the long-term use of GH in these patients.     

Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth

Most children born small for gestational age (SGA) experience extensive catch-up growth during the first months of life (87%) and by the age of 2 years only 13% are below -2 SDS for height. The long-term outcome, including pubertal growth spurt, of the subset of children born SGA without postnatal catch-up (SGAWPC) has been evaluated in very few surveys, and in none of them was the landmarks of puberty well described. Thus, a longitudinal study was conducted in these children throughout puberty since this is the only reliable way to accurately evaluate the pubertal growth spurt. In an observational, retrospective and multicenter collaborative study, from an initial group of 553 SGA children, a subset of 15 boys (BW = 2,070 +/- 379.6 g) and 16 girls (BW = 2,244 +/- 331.1 g) SGAWPC whose data were recorded regularly during puberty were selected. Growth standards for growth and maturity during puberty were Tanner and Whitehouse and Spanish Hernandez and Sobradillo charts. In pubertal growth spurt, 'take-off' occurred later than in the reference populations with a height SDS deficiency of -2.3 and -2.2 for boys and -2.0 and -1.9 for girls, compared with Spanish and Tanner references, respectively. Peak height velocity was normal in chronology and intensity, but the total pubertal gain was smaller. However, considering their growth from the same chronological age at which the reference populations took off until adulthood, the total gain was not significantly different in the three cohorts (32.5 +/- 5.4 cm vs 30.9 +/- 4.4 in boys, and 23.3 +/- 4.1 vs 25.7 +/- 5.4 cm in girls - Spanish reference - and 27.2 +/- 6.3 vs 27.6 +/- 3.5 cm in boys - Tanner charts), except in the case of girls (21.1 +/- 3.9 vs 25.3 +/- 4.1 cm, p <0.005 - Tanner charts). Adult height was significantly reduced (161.9 +/- 3.9 cm in males and 147.0 +/- 2.6 cm in females). Therefore, although the pubertal growth was smaller in these children, puberty probably did not modify their short final height.