Growth of anorexic adolescents

Growth and puberty were studied in 19 children with anorexia nervosa (15 girls and 4 boys), the onset being before puberty or in its early stages. Growth retardation reached 2.04 +/- 1.39 SD, with important individual changes and for some patients a prolonged interruption of growth. Seventeen of 19 patients presented delayed puberty, and in some, hypogonadism persisted after recovery from anorexia nervosa. Endocrine investigations concerning the pituitary somatotropic (GH) and gonadotropic (FSH, LH) secretions, as well as gonadal steroids showed highly variable changes from one patient to another and even variations in the same patient from one test to another. However, no correlation could be found between the hormonal abnormalities and the degree or length of undernutrition. Some patients recovered normal endocrine function when they reached an adequate weight, others kept a lasting deficiency. The endocrine impairment in anorexia, well known in adults, is probably more severe in adolescents.     

Management of puberty in growth hormone deficient children

The pubertal growth spurt accounts for approximately one-eighth of adult height and is regulated by complex hormonal interactions involving the somatotropic and gonadal axes. The observation that children with growth hormone deficiency (GHD) may fail to achieve an appropriate pubertal growth spurt led to the development of strategies to optimize GH therapy during puberty. In one strategy the dosage of GH is increased during puberty to support pubertal growth and in keeping with the physiological increase in serum levels of the hormone seen at that age. A different approach is to combine a GnRH analog (GnRHa) to GH to stop pubertal development, delaying epiphyseal fusion and prolonging peripubertal growth. Both strategies require caution. As regards the first strategy, too high doses of GH may shorten the pubertal time for growth; we found a small, nonsignificant, improvement in final height by increasing the dose by less than half. Preliminary results on the second strategy are more encouraging. However, manipulation of puberty should be limited to selected patients who show a statural height SDS for bone age unfavorable in terms of height prognosis.     

Response to growth hormone treatment and final height after cranial or craniospinal irradiation

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.     

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.     

Induction of puberty in hypogonadal children

Puberty is the transitional period between childhood and adulthood when physical, sexual, and psychosocial maturation occurs. The onset of puberty is controlled by the gonadotropin-releasing hormone (GnRH) neuron and is triggered when inhibition of the neuron is lifted. Subsequently, GnRH induces secretion of other hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate the gonads. Concurrently, increases in estrogen levels in both boys and girls stimulate growth hormone (GH) and insulin-like growth factor-I (IGF-I) secretion, which are responsible for the pubertal growth spurt. In hypogonadal children, however, hypothalamic/pituitary defects or gonadal diseases preclude the production of these hormones, preventing the onset of puberty. Hormone replacement therapy with either estrogen or testosterone is a viable treatment option for hypogonadal children. These should be administered with consideration of sexual maturation rates, statural and bone growth rates, and occurrence of adverse effects. The merits and disadvantages of various hormone replacement therapies for girls and for boys are discussed.     

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.     

Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure

The pubertal growth spurt has been associated with changes of physiologic pulsatile growth hormone (GH) secretion, and abnormalities of the central regulation of GH release have been found by pharmacologic testing in patients with chronic renal failure. To assess the characteristics of GH pulsatility in chronic renal failure and their relationship to pubertal growth, we studied spontaneous nighttime GH plasma profiles in 80 patients (61 boys) aged 10 to 20 years receiving conservative treatment (n = 29) or dialysis (n = 18) or after renal transplantation (n = 33). Tanner genital stages 1 to 4 in boys and breast stages 1 to 3 in girls were represented. Growth hormone pulse analysis was performed by the PULSAR algorithm. Growth hormone concentration profiles were pulsatile in each patient. Growth hormone mean and baseline levels and pulse amplitudes were higher in patients receiving conservative or dialysis treatment than in patients who had undergone renal transplantation. Peak frequency was similar in all treatment groups in boys but higher in girls who had undergone transplantation than in girls receiving conservative or dialysis treatment. Growth hormone peak amplitude and mean levels were lowest in patients in late puberty. The physiologic elevation of GH amplitudes around midpuberty was observed in boys receiving conservative and dialysis treatment but not after transplantation. Growth hormone mean and baseline levels were positively correlated with plasma androgen levels in boys. Growth hormone peak amplitude was correlated with 6-month height velocity after transplantation but not in patients receiving conservative treatment or dialysis. A strong inverse relationship was observed between GH peak amplitude and corticosteroid dosage in patients undergoing transplantation. The lack of relationship between circulating GH levels and growth in patients receiving conservative or dialysis treatment is compatible with end-organ hyporesponsiveness to GH. Pubertal growth failure despite successful transplantation appears to be related to steroid-induced GH hyposecretion.     

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.     

Subnormal Growth During Puberty in Children Treated for Acute Lymphoblastic Leukemia

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

Management of Growth Hormone Deficiency Through Puberty

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

Cerebral irradiation causes blunted pubertal growth in girls treated for acute leukemia

The improved treatment of childhood leukemia is a major achievement. The late effects of the treatment need further investigation. Growth inhibition has been demonstrated in earlier studies. Growth and the timing of puberty were studied in 179 girls who had been treated for acute lymphoblastic leukemia (ALL) in Denmark, Finland, Norway, and Sweden. The patients were divided into two groups according to mode of CNS prophylaxis: with or without cerebral irradiation. Longitudinal analysis of 103 patients showed no difference in prepubertal growth in irradiated and nonirradiated girls. Growth during puberty was normal in girls without irradiation and below normal in irradiated girls. There was no difference in growth between girls after 24 Gy or 20 Gy of cerebral irradiation. Irradiated girls had a final height which was one SD less than expected before puberty and menarche occurred one year earlier than in the nonirradiated girls. Prophylactic cerebral irradiation is the most important factor for subnormal growth after treatment for ALL. There is no short-term influence on growth but the effects of irradiation become apparent several years after therapy when girls enter puberty somewhat early and have a subnormal pubertal growth. Growth and growth hormone (GH) levels should be evaluated several years after CNS irradiation, and treatment with GH and/or luteinizing hormone releasing hormone (LHRH) analogues may be considered. © 1994 Wiley-Liss, Inc.     

Effects of human growth hormone on very short children with intermediate responses to somatotropic stimulation tests

The effects of treatment with human growth hormone (hGH) were studied in 29 patients aged 2 to 16 years with growth retardation between 2.2 and 6 standard deviations and insufficient growth velocity in whom repeated pharmacologic somatotropic stimulation tests had shown discordant responses either above 7 ng/ml, or lower than 6 ng/ml. An important acceleration of growth was obtained in 10 of 16 patients before puberty and in all the 13 cases treated at the beginning of puberty. No correlation was observed between the GH levels observed during the stimulation tests and the clinical results of treatment. These data lead to discuss partial GH deficiency and to propose a trial of treatment in very short children with low and/or dissociated responses to repeated tests of pituitary somatotropic secretion.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Gender does not influence prepubertal growth velocity during standard growth hormone therapy--analysis of United States KIGS data

BACKGROUND: Gender is an important determinant that affects the ultimate dose of growth hormone (GH) used for replacement in adult GH deficiency (GHD). Women require larger doses of GH per body weight to achieve comparable age-adjusted serum IGF-I concentrations than do men. OBJECTIVE: To test whether this is entirely a sex steroid effect or biologically inherent in gender. PATIENTS AND METHODS: We examined growth response to GH (0.25-0.35 mg/kg/week) during the first 2 years of therapy in 147 children (44 girls), and in the first 3 years of therapy in 83 of these children (23 girls). Children were aged 3-8 years at onset of therapy, had peak stimulated GH <10 microg/l, and were reported to be prepubertal during the period of analysis. RESULTS: In the relative absence of sex steroid, there was no gender difference in growth velocity SDS or gain in height SDS during 2 or 3 years of GH therapy. CONCLUSIONS: Inherent gender differences in linear growth response to GH prior to puberty may exist, but are not evident in the first years of GH therapy at this GH dose.     

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

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

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

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

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

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

Priming with testosterone enhances stimulated growth hormone secretion in boys with delayed puberty

BACKGROUND AND OBJECTIVE: Tests for growth hormone (GH) deficiency are not always helpful in the differential diagnosis of physiological delay of growth and puberty and GH deficiency. PATIENTS AND METHODS: To enhance diagnostic specificity, we used a single dose testosterone priming before repeating the arginine stimulation test in 26 boys with short stature and only early signs of puberty who failed to show an adequate response of serum GH in the first test. RESULTS: 77% (20/26 patients) increased their serum GH peak to more than 10 ng/ml, whereas six patients were still below this concentration. CONCLUSION: We propose that testosterone priming is a useful tool to distinguish between physiological delay of growth and puberty and GH deficiency and should be included in the diagnostic procedure.     

A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong

Methodology: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major.
Results Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4±0.1 mU/mL vs 0.37±0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 ± 0.2 U/mL vs 0.56 ±0.14 U/mL, P= 0.26).
Conclusions Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major.     

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

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