Mean Height Velocity Research Articles

Suppression of the Pituitary-Gonadal Axis in Children with Central Precocious Puberty: Effects on Growth, Growth Hormone, Insulin-Like Growth Factor-I, and Prolactin Secretion*

To assess further the relationship between gonadal sex steroids and PRL, GH, and insulin-like growth factor-I (IGF-I) secretion and to help clarify the mechanism underlying the pubertal growth spurt, we studied 11 children (10 girls) with central precocious puberty before and during gonadal suppression with the GnRH agonist (GnRH-a) leuprolide acetate. Nocturnal sampling for plasma levels of GH and PRL, GH response to GH-releasing factor-(1-44), and plasma IGF-I levels were determined before and 3-6 months after pituitary-gonadal suppression. Treatment caused a significant decrease in the LH and FSH responses to GnRH (P less than 0.01) and the plasma concentration of estradiol (P less than 0.05). The patients' mean height velocity SD score for chronological age, initially 3.8 +/- 1.9, decreased significantly to 0.9 +/- 0.9 with treatment (P less than 0.005). Nocturnal GH secretion (mean GH concentration, sum of GH pulse areas, sum of GH pulse amplitudes, and GH pulse frequency) and mean IGF-I levels (1.38 +/- 0.6 vs. 1.72 +/- 0.34 U/mL) were not significantly altered by treatment. However, the mean peak GH response to GH-releasing factor-(1-44) was 29.2 +/- 6.8 micrograms/L before treatment and declined significantly to 17.7 +/- 3.4 micrograms/L after gonadal suppression (P less than 0.05). PRL secretion was similar before and after GnRH-a-induced suppression. These results indicate that the decrease in height velocity noted during GnRH-a treatment occurred independently of changes in nocturnal GH secretion and IGF-I levels. These data are consistent with the premise that sex steroids can modulate growth by a direct action on skeletal growth.

Growth‐Promoting Effect of Human Growth Hormone on Patients with Achondroplasia

To evaluate the effect of human growth hormone (hGH) on the growth of children with achondroplasia, three patients with achondroplasia and one patient with hypochondroplasia were treated with 0.5 IU/kg/W of pituitary-extracted hGH for 6-12 months. Mean height velocity was significantly increased from 4.0 +/- 0.4 to 7.5 +/- 0.7 cm/year (P less than 0.05) by hGH. The tibial index, defined as the length/width ratio of left tibia, did not change during the treatment, indicating that hGH promotes growth without exaggeration of tubular bone deformity. Case 2, who had atlantoaxial dislocation, developed sleep apnea and neurological deficits during the second hGH treatment, but these were cured by operation. Thus, hGH therapy is effective in promoting growth in patients with achondroplasia, but the complication of atlantoaxial dislocation should be explored and corrected before the treatment.

Factors influencing postoperative recurrence of Crohn's disease in childhood.

We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn's disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). The mean height velocity of patients with growth potential increased from 2.4 (2.3) cm per year preoperatively to 8.1 (3.4) cm per year in the first postoperative year (p=0.0001). These results support an early approach to surgery in the management of ileal Crohn's disease with or without caecal or right colonic involvement, especially when complicated by persistent growth failure. The higher recurrence rates in more diffuse ileocolonic disease emphasise the need for alternative treatment strategies in these children.

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF‐I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.

Effectiveness of Growth-Promoting Therapies

The ability of growth hormone, clonidine, and levodopa to stimulate growth was compared in short and slowly growing children randomly assigned to different treatment regimens for 6 months. There were 10 children in each group, and 10 additional subjects served as controls. Growth hormone improved mean height velocity, height velocity SD score, and height SD score. The mean height velocity and height velocity SD score were significantly increased by clonidine, while levodopa only enhanced the mean height velocity SD score of the treated children. Moreover, in nine patients (90%) receiving growth hormone, two (20%) receiving clonidine, and one (10%) receiving levodopa, the height velocity was raised by more than 2 cm/y. The increments in height velocity and height SD score were greatest in the growth hormone group. Clonidine induced an increase in height velocity significantly different from that in control children only. In the control group, there was a significant reduction of height SD score with time.

Longitudinal growth in children with non‐Hodgkin's lymphoma and children with acute lymphoblastic leukemia: Comparison between unirradiated and irradiated patients

Longitudinal growth was studied in children treated for non-Hodgkin's lymphoma (NHL). The aim of the study was to compare these children's growth velocity with findings in a previous study we performed on age-matched children with acute lymphoblastic leukemia (ALL) who received cranial irradiation. Nine children with NHL with an onset time of treatment between 4 and 9 years of age (mean 6.5 years) were studied with annual body measurements taken from the time of the diagnosis and thereafter annually during the following 4 years. None of the children received cranial irradiation. During the first treatment year a significantly low mean height velocity was observed (-1.4 standard deviation score [SDS]) for the NHL group. The consecutive two 1 year periods showed a normalization of the mean height velocity. For the group of children with ALL, there was a more prominent negative effect on height during the first 2 years of treatment than for the NHL group in the present study. After the cessation of therapy, the children with NHL showed a reduced catch-up growth compared with the children with ALL. The explanation offered is that cranial irradiation has a heavier impact on growth than chemotherapy during the first 2 years of treatment, but an intense chemotherapy during the maintenance period could have a considerable impact in blunting growth.

Gonadotrophin‐Releasing Hormone Analogues as Therapeutic Probes in Human Growth and Development: Evidence from Children with Central Precocious Puberty

Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (delta BA/delta CA = 0.6 +/- 0.1 over 3 years, mean +/- SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective.

The Pubertal Growth Spurt in Eight Patients with True Precocious Puberty and Growth Hormone Deficiency: Evidence for a Direct Role of Sex Steroids*

The relative contributions of GH, insulin-like growth factor-I (IGF-I), estradiol, and testosterone to the pubertal growth spurt are incompletely understood. We studied 8 patients (5 girls and 3 boys) with true precocious puberty and GH deficiency due to CNS lesions to assess the role of sex steroids in pubertal growth independent of an increase in circulating GH. Included is 1 patient with an unusual hypothalamic lesion due to head trauma. A control group of 17 GH-sufficient patients with true precocious puberty (13 girls and 4 boys) was matched for chronological age. The GH-deficient girls grew at a mean velocity of 9.2 cm/yr (range, 7.2-14.4), and the boy's mean height velocity was 7.9 cm/yr (6.1-9.9). Mean bone age was advanced in the GH-deficient group (girls, +2.7 SD; boys, +2.6 SD), but not as much as the GH-sufficient controls (girls, +5.4 SD; boys, +4.3 SD). The mean concentration of plasma IGF-I was lower in the GH-deficient group than in the control group, but was greater than the mean concentration in age-matched prepubertal GH-deficient patients. Four GH-deficient patients were treated with a potent agonist of LRF. This caused suppression of gonadal sex steroid concentrations and a fall in mean height velocity from 9.1 to 4.3 cm/yr after 1 yr of therapy; however, circulating GH and IGF-I values were not uniformly altered. We conclude that a substantial pubertal growth spurt can occur in patients with true precocious puberty and GH deficiency that is dependent on gonadal sex steroids yet unaccompanied by normal pubertal levels of circulating GH or IGF-I. Reversal of this growth acceleration is possible with sex steroid suppression. The results, in light of previous in vivo and in vitro studies, suggest that the normal pubertal growth spurt is mediated in part by direct effects of sex steroids at the growth plate.

Two‐Year Results of Treatment with Methionyl Human Growth Hormone in Children with Turner Syndrome

Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m2 body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 microgram/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.

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

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 = 45), 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 (delta BA/delta CA = 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 zeta-scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, delta BA/delta CA, and the change in height SDS for BA (delta HT 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.

Biosynthetic Human Growth Hormone in the Treatment of Growth Hormone Deficiency

A total of 309 previously untreated children with growth hormone deficiency (GHD) (219 boys, 90 girls; mean age 8.4 +/- 3.9 years, range 1.5-19 years) were treated for up to 3 years in an ongoing trial designed to examine the long-term efficacy and safety of biosynthetic somatropin (rhGH). The children were treated with rhGH, 0.06 mg/kg (0.16 IU/kg) three times weekly. In the prepubertal children, the mean height velocity increased during the first year from 3.8 +/- 1.8 cm/year to 8.9 +/- 2.2 cm/year (n = 188). During the second and third years, their height velocities were 7.1 +/- 1.1 (n = 147) and 6.3 +/- 1.2 cm/year (n = 64), respectively. The height velocity SDS increased from -2.5 +/- 1.9 before treatment to 3.1 +/- 2.6 during the first year of treatment in the prepubertal children. The mean pretreatment height velocity in those with idiopathic GHD (3.8 +/- 1.6 cm/year) did not differ from that in children with organic GHD (3.8 +/- 2.3 cm/year). In addition, the height velocities during the first year of therapy did not differ significantly with respect to the aetiology of GHD. For the children who entered puberty during the study, the mean height velocity increased from 3.0 +/- 1.7 cm/year before treatment to 8.4 +/- 2.3 cm/year during the first year of rhGH therapy. In the first year, the height velocity of children with a bone age of less than 5 years (9.4 +/- 2.3 cm/year) was significantly greater than that in children with a bone age of 5-10 years (8.4 +/- 1.8 cm/year) or greater than 10 years (7.8 +/- 2.2 cm/year: p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Short‐Term Growth Hormone Therapy in Short Children without Growth Hormone Deficiency

Evaluation of 24-hour endogenous growth hormone (GH) secretion was carried out in 62 children, aged 7-16 years, who did not have classic GH deficiency (GHD). The mean 24-hour GH concentration, determined at 20-minute intervals over 24 hours, was variable, ranging from 1.28 to 11.39 micrograms/l with a mean of 4.95 +/- 2.55 micrograms/l (+/- SD). There was a positive correlation between mean 24-hour GH concentration and plasma insulin-like growth factor I (IGF-I) values (r = 0.54; p less than 0.01). Recombinant human GH, 0.1 IU/kg/day was administered to 30 of the 62 children for 6 months followed by 6 months' observation without treatment. Thereafter, GH was administered at the same dose for a further 6 months to 16 children. The mean height velocities before, during, and after the first treatment period were 4.3 +/- 0.9, 7.3 +/- 1.9 and 4.9 +/- 2.0 cm/year (mean +/- SD), respectively. The height velocity during treatment was greater than pre- and post-treatment values (p less than 0.001). The height velocity increased again during the second treatment period to a mean of 8.5 +/- 2.0 cm/year (p less than 0.001). Nine other children were treated continuously in a similar manner for 1 year and their height velocity increased significantly from 4.1 +/- 1.4 to 6.0 +/- 1.9 cm/year (p less than 0.001). According to our criteria, 29 of the 39 children (74.4%) who were treated for 6-12 months showed a GH-dependent height increase during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth-Promoting Effect of Growth Hormone and Low Dose Ethinyl Estradiol in Girls with Turner's Syndrome*

Forty patients with Turner's syndrome, aged 5.0-16.6 yr, were randomly allocated to receive daily sc injections of recombinant human GH (hGH) at a dose of 1 IU/kg.week alone (group I) or in combination with 25 ng/kg.day ethinyl estradiol (E2; group II). The mean pretreatment height velocity was 3.8 cm/yr for both groups. During the first year of treatment height velocity increased significantly (P less than 0.001) in both groups, to 7.5 +/- 1.3 and 8.1 +/- 1.6 cm/yr, respectively. The difference between the two groups was not significant. The mean (+/- SD) height velocity expressed as the SD score for chronological age (Turner references) was 0.0 +/- 1.2 for group I and 0.2 +/- 1.4 for group II and increased significantly (P less than 0.001) during the first year of treatment to +4.3 +/- 1.1 in group I and +5.4 +/- 1.2 in group II. The difference between both groups was statistically significant (P less than 0.01). Height SD score for chronological age (Turner references) increased from -0.2 +/- 0.9 to +0.6 +/- 1.0 in group I and from -0.2 +/- 1.0 to +0.7 +/- 1.1 in group II. Mean bone age progressed similarly in both treatment groups (1.1 +/- 0.6 yr during 1 yr of treatment). However, bone age maturation accelerated more rapidly in younger patients. Twelve girls (three in group I and nine in group II) had minor breast development. No major adverse effects were reported. We conclude that daily sc therapy with hGH stimulates height velocity in Turner's syndrome. The beneficial effect on height velocity increment of E2 addition was small. Furthermore, even very low doses of E2 may induce breast development at an early age and accelerate bone maturation. For these reasons, the addition of E2 to hGH is not warranted in young patients with Turner's syndrome.

Oxandrolone in constitutionally delayed growth, a longitudinal study up to final height.

Twenty-seven prepubertal boys and 9 prepubertal girls with constitutionally delayed growth were treated with the anabolic steroid oxandrolone for 12 months and followed until they reached final height. Sixteen boys were treated with a mean dose of 0.12 mg/kg.day [low dose (LD)] and 11 boys with a mean dose of 0.22 mg/kg.day [high dose (HD)]. The girls were treated with a mean dose of 0.1 mg/kg.day. Thirteen boys and 9 girls served as controls. On oxandrolone the mean height velocity increased from 4.0 to 8.6 (boys, LD), from 4.3 to 8.9 (boys, HD), and from 4.3 to 8.3 cm/yr (girls). The immediate posttreatment height velocity was significantly higher than the pretreatment height velocity (P less than 0.05), regardless of whether the patients had entered puberty. On oxandrolone the mean ratios of change in bone age/change in chronological age were 2.0 (boys, LD), 2.3 (boys, HD), and 2.0 yr/yr (girls) and continued to be accelerated during the 6 months after treatment. Height predictions at the onset of treatment and after 6 months off treatment were calculated by three different methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner Mark II (T II). In the boys (LD) mean height predictions increased significantly by the methods of BP (3.3 cm) and RWT (2.9 cm), but not by the method of T II (0.6 cm). In the boys (HD) no significant change in height predictions was noted. In the girls mean height predictions remained unchanged by BP and RWT, but decreased significantly by T II (-2.5 cm). The difference between final height and initial height prediction was taken as a measure of the influence of the treatment on adult height. In all three treatment groups the difference between final height and initial height prediction, calculated with all three methods, did not differ from the control group. We conclude that oxandrolone treatment for 1 yr has no effect on adult height. In spite of this, the use of an anabolic steroid such as oxandrolone may still have value, as an increase in height velocity and an earlier onset of puberty may benefit short children suffering from psychological problems due to delay of growth and development.

Effects of two years of methionyl growth hormone therapy in two dosage regimens in prepubertal children with short stature, subnormal growth rate, and normal growth hormone response to secretagogues

Thirty short, slowly growing children with normal plasma growth hormone response to standard provocation tests were randomly assigned to a group (n = 20) undergoing therapy with methionyl growth hormone, 2 IU/m2 subcutaneously once daily, (group 1) or a control group (n = 10, group 2). The mean (+/- SD) height velocity increment in group 1 was 3.0 +/- 1.9 cm/yr in the first year, compared with -0.2 +/- 0.7 cm/yr in group 2. Of the 18 children who completed the first year of treatment, 12 had a height velocity increment of more than 2 cm/yr and 11 of them continued treatment for a second year (group 1A). The remaining six children also reached height velocities greater than the mean for bone age, but because of a low height velocity increment they were termed nonresponders and their growth hormone dosage was increased to 4 IU/m2/day (group 1B). Of the 10 children in the control group, seven received authentic biosynthetic growth hormone in the second year of the study (group 2); the remaining three received no therapy (group 3). The mean height velocities (measured in centimeters per year) before and during the first and second years of therapy were 3.6, 7.6, and 6.1 in group 1A; 5.7, 6.9, and 7.3 in group 1B; 4.2, 4.0, and 6.7 in group 2; and 5.0, 4.9, and 5.2 in group 3. The effect of doubling the dosage was a further increase of 1.9 cm/yr. Bone age advance paralleled growth acceleration, resulting in an unchanged height standard deviation score for bone age and ambiguous results on final height prediction. Growth hormone therapy in such short children appears to be safe and efficacious in increasing growth velocity for 2 years, but its efficacy in terms of increasing final height is uncertain.

Criteria for recognition of the growth-inefficient child who may respond to treatment with growth hormone.

In this study three groups of short children composed of 104 subjects (61 boys, 43 girls) were evaluated for spontaneous secretion of growth hormone (GH). Group 1 consisted of 10 subjects (6 boys, 4 girls) with "classic" GH deficiency. Group 2 consisted of 31 subjects (17 boys, 14 girls) with "nonclassic" GH deficiency. Group 3 consisted of 63 subjects (38 boys, 25 girls) with short normal stature. Blood samples were drawn every 20 minutes over 24 hours, and the mean GH concentration, nocturnal GH concentration, diurnal GH concentration, pulse amplitude, and number of pulses with a GH peak above 5 micrograms/L were determined. The values for mean height, height velocity, bone age to chronological age ratio, somatomedin C concentration, GH concentration, nocturnal GH concentration, diurnal GH concentration, pulse amplitude, and number of pulses with a GH peak over 5 micrograms/L were significantly greater in group 3 than in group 2, and these same values, except for the mean diurnal GH concentration, were greater in group 2 than in group 1. The mean GH concentration correlated with the mean nocturnal GH concentration. Subjects in groups 1 and 2 were treated with GH for 1.23 +/- 0.53 years (mean +/- SD). All the group 1 subjects and 27 (87%) of the group 2 subjects responded with an increase in height velocity greater than 2 SDs per year of therapy. In conclusion, 87% of subjects with a normal GH response to provocative stimuli testing who had a mean height velocity of less than 4 cm/y, mean height lower than the third percentile, mean bone age to chronological age ratio of less than 0.8, and mean GH concentration less than 3 micrograms/L responded to GH therapy.

The Wessex Growth Study: first report.

The Wessex Growth Study is a community-based longitudinal survey of short children recruited from two Health Districts in Wessex during 1985-86 (cohort I) and 1986-87 (cohort II). Screening of new school entrants during 1985-86 identified only 1.3% who were at or below the 3rd centile for height as defined by Tanner and Whitehouse, suggesting a strong secular trend and an urgent need for updated height charts. After exclusion of the small number of children with underlying organic pathology and those from ethnic minorities, there were 84 children in cohort I on whom this report is based. These apparently normal, short children were sex- and age-matched with normal controls (10th-90th centile) from the same school class. Forty-two per cent of cohort I had a delayed bone age, and 34% lay above the 3rd centile after correction for parental height. Forty-four per cent were of low birth weight. The correlation between two successive height velocities measured at 6 and 12 months was only -0.14 for cohort I and -0.15 for their controls. Twelve-month mean height velocity SD scores (SDS) were -0.45 and +0.25, respectively, corresponding to the 33rd and 60th centiles, and rather higher than the 25th and 50th centiles expected in view of the heights of these children. Thirty-eight per cent of cohort I had a 12-month height velocity below the 25th centile, and in 16% height velocity was below the 10th centile. As a group, the children in cohort I grew more slowly than their controls, but the height velocity in 88% of cases lay within the control range.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological Growth Hormone Secretion and Response to Growth Hormone Treatment in Children with Short Stature and Intrauterine Growth Retardation

Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of less than 20 mU/l during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m2/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from -0.61 to +1.09, and the group treated with 30 U/m2/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.

Testosterone Treatment in Adolescent Boys with Constitutional Delay in Growth and Development

The administration of androgens to adolescent boys with constitutional delay in growth has been highly controversial because of the possibility of premature epiphyseal closure and reduced final height. We have treated 15 such boys with a mean (+/- SD) age of 14.1 +/- 1.0 years and a mean initial height of 142.2 +/- 8.6 cm (range, 127.1 to 156.2). The boys received monthly intramuscular injections of testosterone enanthate (50 mg) for 1.2 +/- 0.3 years. The mean height velocity rose from the 3rd percentile for mean skeletal age to above the 90th percentile, where it remained throughout treatment. Although skeletal maturation accelerated initially in the seven boys with a skeletal age under the pretreatment group mean of 11.3 years, it advanced normally in the others. The concomitant increase in stature was sufficient to offset the advancement in skeletal age in most boys, so that the mean predicted adult height was essentially unaffected. Sexual maturation also progressed; testicular volume increased from 5.9 +/- 2.7 to 11.3 +/- 2.7 ml. After treatment, the skeletal age advanced normally and sexual development continued. Eight of the boys are now 18.1 +/- 0.5 years of age and have stopped growing; their present mean height (167.6 +/- 4.7 cm) is very close to their pretreatment predicted height of 168.0 +/- 5.6 cm. We conclude that low-dose testosterone treatment is effective in adolescent boys with delayed growth and development and that it does not appear to compromise final adult height.

137 IMPORTANCE OF BONE AGE (BA) FOR SUBSEQUENT RESPONSE TO BUSERELIN THERAPY INCENTRAL PRECOCIOUS PUBERTY (CPP)

In patients with CPP, we lack criteria to determine optimal age when GnRH agonist therapy should be stopped. In 18 patients with CPP (16 girls, 2 boys) treated with buserelin intranasally (1.2 to 1.8 mg/day) for 1 to 3 yrs (mean: 2.3 yrs), we examined whether BA affected the subsequent rates of growth and of bone maturation. During therapy, pubertal development showed regression in 10 patients and arrest in 8, while mean (± ISD) height velocity (pretreatment, 10.7 ± 3.6 cm/yr) decreased to 6.5 ± 1.5, 4.6 ± 1.4 and 3.6 ± 1.2 cm/yr after 1, 2 and 3 yrs of treatment, respectively. In order to evaluate the growth rates vs the rates of bone maturation, SD Scores (SDS) of height for BA (TW2, RUS) were calculated before and during the 1st, 2nd and 3rd yrs of therapy. The difference in SDS of height for BA observed during therapy (range: -1.2 to +1.2 SD) were directly related (r = +0.51) to BA (range: 10,1 to 13.7 yrs). This was because increase in BA resulted in a reduced ΔBA/ΔCA (range: 1.9 to 0.1, r = -0.58). Thus, although height velocity is decreasing with age and duration of buserelin therapy, the concomitant reduction in BA velocity results in an apparent growth saving effect occurring with advancement in BA. Therefore, study of BA does not provide arguments for stopping GnRH agonist therapy. Possible criteria related to the capacity af achieving a residual growth spurt after stopping treatment warrant further evaluation.