Birth of a boy with isolated short stature after prenatal diagnosis of a Xp22.3 nullosomy due to an inherited t(X;15) (p22.3;p10) translocation.

KEY CLINICAL MESSAGE: Translocations between X and acrocentric chromosomes are rare. We report on the inheritance of a familial t(X;15)(p22.3;p10) translocation in a fetus referred for short long bones. Cytogenetic analysis revealed an unbalanced translocation combined with a three-gene nullosomy. After genetic counseling, a prognosis was established and a healthy boy was delivered.

Characterization and prevalence of severe primary IGF1 deficiency in a large cohort of French children with short stature.

OBJECTIVE: The prevalence of severe primary IGF1 deficiency (IGFD) is unclear. IGFD must be identified promptly as treatment with recombinant human IGF1 (rhIGF1) is now available. Our objective was to characterize and assess the prevalence of severe primary IGFD in a large cohort of patients evaluated for short stature at a pediatric endocrinology unit in France. DESIGN: Observational study in a prospective cohort. METHODS: Consecutive patients referred to our unit between 2004 and 2009 for suspected slow statural growth were included. Patients were classified into eight etiological categories. IGFD was defined by height ≤-3 SDS, serum IGF1 levels <2.5th percentile, GH sufficiency, and absence of causes of secondary IGFD. RESULTS: Out of 2546 patients included, 337 (13.5%) were born small for gestational age and 424 (16.9%) had idiopathic short stature. In these two categories, we identified 30 patients who met our criterion for IGFD (30/2546, 1.2%). In these 30 patients, we assessed the response to IGF1 generation test, time course of IGF1 levels, and efficiency of GH replacement therapy. The results indicated that only four of the 30 children were definite or possible candidates for rhIGF1 replacement therapy. CONCLUSION: The prevalence of severe primary IGFD defined using the standard criterion for rhIGF1 treatment was 1.2%, and only 0.2% of patients were eligible for rhIGF1 therapy.

[Integration to school of young children with type 1 diabetes on insulin pump therapy: parent's feed-back]. / Expérience des parents sur l'intégration des jeunes enfants diabétiques traités par pompe à insuline en crèche et à l'école : enquête en région Ile-de-France.

There is an increase in the incidence of type 1 diabetes (T1D) in children younger than 5 years of age and continuous subcutaneous insulin infusion (CSII) appears to be an increasingly popular therapeutic option in France. A retrospective self-evaluation questionnaire was distributed to parents of young children with T1D treated by CSII (42 children, age 4.8±1.0 years, 2.3±0.5 years at the onset of TD1, mean± SD). It focused on the quality of diabetes management in daycare centers or with nannies and at school. Parental satisfaction related to the management of their children was overall good (84% for all the parents, 70.5% for the parents of children at nursery-school, from 3 to 6 years. However 93% of the parents experienced and overcame serious difficulties: exclusion of the children on account of DT1 (school trips, daycare centers after school), use of the pump for lunch and snacks, realization of glycemic controls, participation in school trips, survey during school meals. In spite of these difficulties these young children had a normal and safe time at school. The management of the young children with DT1, treated by CSII, in alternate care centers and at school need to be improved; the experience was positive when daycare workers and teachers agreed to be instructed.

Variable outcome of growth hormone administration in respiratory chain deficiency.

Genetic defects of oxidative phosphorylation (OXPHOS) are known to account for a variety of neuromuscular and non-neuromuscular symptoms in childhood, including growth hormone (GH) deficiency. However GH administration for GH deficiency is controversial in OXPHOS deficiencies as GH is a mitosis-stimulator which may increase energy demand for cell proliferation. Here, we report the observation of four unrelated children with OXPHOS deficiency or bearing a mitochondrial DNA rearrangement and growth retardation, who required GH therapy. The first patient had no GH deficiency while the other three had low GH response to test stimulations. The condition of the first two patients quickly deteriorated under GH administration, GH was then stopped and subsequent clinical improvement was noted. In the other two patients, no adverse event was noted but various additional organs were involved following GH administration. In all patients, no benefit was observed concerning growth response as growth speed remained unchanged. These observations question the use of GH as a treatment of growth retardation for patients with OXPHOS deficiency.

Effects of growth hormone on growth factors after renal transplantation.

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4 +/- 1.1 years and a mean bone age (BA) of 7.3 +/- 0.9 years. Mean height was -3.9 +/- 0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9 +/- 0.6 and the mean inulin clearance was 36.5 +/- 4.9 ml/min/1.73 m2. Recombinant hGH was given at 4 IU/m2/day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P < 0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P < 0.01) by about 100% (mean values after GH therapy: 95.9 +/- 2.1 nM and 165 +/- 29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148 +/- 18 pM, P < 0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy.

Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement.

Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.

Effects of growth hormone in short children after renal transplantation. French Society of Pediatric Nephrology.

From 1991 to 1993, 90 children having received a kidney graft with a post-transplantation period of at least 12 months were included in a prospective study carried out in 18 French pediatric centers. After informed consent and randomization, children received recombinant human growth hormone (rhGH) (Genotonorm, Pharmacia peptide hormones) 30 U/m2 per week, either immediately on enrollment, for the treated group, or after 1 year of follow-up for the group serving as a control. After 1 year both groups were treated and we analyzed data during the subsequent years. Eighty-five children completed the 1-year study. Growth velocity was significantly increased by rhGH: 7.7 cm with a gain of +0.3 standard deviation score in the treated group versus 4.6 cm in the control group (P<0.0001) during the 1st year. Four factors predicted response to therapy: growth velocity prior to GH therapy, glomerular filtration rate (GFR) at the start, mode of corticosteroid administration, and degree of insulin resistance. After 1 year we observed a moderate, significant decrease in GFR in both groups. Biopsy-proven acute rejection episodes were not significantly more frequent during the 1st year in the group of patients who received rhGH: 9 in 44 versus 4 in 46 patients. The patients who rejected did not differ in terms of age, renal function at the start, and type of immunosuppression, but history of rejection before GH treatment was discriminatory: 6 of 17 children with two or more episodes had a new rejection versus 1 of 22 who had no or only one episode (P=0.01). Glucose tolerance was not modified after 1 year of GH therapy. During the subsequent years of treatment a decrease in growth velocity was noted: 5.9 cm at 2 years, 5.5 at 3 years, and 5.2 cm at 4 years. In conclusion, GH is efficient for improving growth velocity in short transplanted children, inducing clear-cut but limited catch-up growth. The risk of rejection was shown only in patients with a prior history of more than one rejection episode.

Recombinant human growth hormone treatment of children on hemodialysis. French Society of Pediatric Nephrology.

Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0 standard deviation score (SDS) for age, were selected to receive recombinant human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36 were prepubertal and 8 were in early puberty (testicular volume between 4 and 8 ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week by daily subcutaneous injection for 1-5 years. The year before rhGH therapy served as a control period. During the 1st year of treatment, mean growth velocity increased from 3.5 to 7.0 cm/year (P < 0.0001) and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years (P < 0.0001), but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity (P < 0.0001), with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year.

[Modalities of transition of diabetic adolescents from pediatrics to the adult care in the Paris-Ile-de-France region: an appeal to cooperative work for improving quality of care. Paris-Ile-de-France Section of DESG (Diabetes Education Study Group) in French language]. / Modalités du passage des adolescents diabétiques de la pédiatrie aux structures pour adultes dans la région Paris-Ile-de-France: un appel au travail collaboratif pour améliorer la qualité des soins. Section Paris-Ile-de-France du DESG (Diabetes Education Study Group) de langue française.

AIM: The purpose of this study was to evaluate the conditions in which diabetic adolescents are transferred from pediatric to adult health care, and to record the opinions of the physicians about this issue. METHODS: A questionnaire-based study was performed among all the pediatricians in the hospital setting and all the diabetologists from the Paris-Ile-de-France area. Questionnaires from 50 pediatricians and 51 diabetologists were completed (response rate: 68%). RESULTS: 1) Not enough information was transmitted: a quarter of the diabetologists were visiting for the first time without any information on the adolescent, and only half the pediatricians received feedback information from the internists after the first visit. And yet, when considered, it was important to be kept informed after the first visit and the following ones. 2) Medical relationships were poor: more than three out of four pediatricians and diabetologists had none or very few professional meetings, and two thirds of them were not aware of the way the others were working. 3) Eighty percent of pediatricians and diabetologists considered that the transfer of diabetic adolescents had to be organised in order to keep the coherence of medical follow-up, to minimise the psychological effects of the transition, and to avoid a complete break in the patient follow-up. 4) The expectations of the pediatricians were: the validation of their previous follow-up through the feedback information from diabetologists and the continuity of the medical follow-up; those of the diabetologists were: to gain the patient's confidence and to master the patient's previous history, in order to provide a better follow-up. 5) According to the opinion of both pediatricians and diabetologists, the main errors to avoid were, by the paediatricians, to miss the time and the preparation of the transfer and, by the diabetologists, to denigrate the previous pediatric management and to change the insulin regimen immediately. CONCLUSION: This study demonstrates a lack of communication between physicians of pediatric and adult health care centres. But it also underlines their recognition of the importance of the transition's stakes and their common motivations in order to improve it.

Human immunodeficiency virus type 2 infection in children.

Human immunodeficiency virus type 2 infection is rare in children. This virus can be acquired through transfusion and also by the maternofetal route, especially when the mother becomes infected during pregnancy. Diagnosis based on specific serologic tests is simple after the age of 18 months. In the perinatal period, however, viral isolation by culture or polymerase chain reaction DNA amplification or both appears to be less sensitive than in the case of human immunodeficiency virus type 1. Disease progression is far slower than with human immunodeficiency virus type 1, but severe immunodeficiency can occur.

A 5-year prospective study of growth hormone (GH)-deficient children treated with GH before the age of 3 years. French Serono Study Group.

The aim of the study was to assess the efficacy of GH therapy in GH-deficient children treated before the age of 3 yr. A noncomparative multicenter prospective study included 49 children (22 girls and 27 boys) with isolated GH deficiency (n = 19) or multiple pituitary hormone deficiency (n = 30) treated with daily s.c. injections (0.6 U/kg.week) for 3-5 yr. They were divided into two groups according to their height SD score for chronological age (CA) at the initiation of therapy: group A consisted of 8 patients presenting an initial height within the normal range (< 2 SD below the mean) followed for 2-5 yr, and group B consisted of 25 children followed for 5 yr among 41 patients with initial growth retardation. In group A, the mean height SD score increased from -1.1 +/- 0.6 to 0.35 +/- 1.0 SD (P < 0.001) in the first year and remained in the normal range throughout the following 4 yr. In group B after 4 yr of treatment, the mean height SD score for age had increased from -3.6 +/- 1.0 SD (time zero) to -0.9 +/- 1.2 SD. During the fourth year of therapy, the mean height gain of 0.2 +/- 0.2 SD was significant (P < 0.001). After 5 yr of treatment, a plateau was reached with a corresponding height SD score (CA) of -0.8 +/- 1.2 SD (95% confidence interval between -1.3 and -0.2 SD). This value remained significantly below normal for age (P < 0.001), indicating that catch-up growth was incomplete. Only four patients (16%) remained below -2SD for CA. The 5-yr height gain was negatively correlated with the height SD score at the start of treatment (r = -0.6; P < 0.005) and the first year height gain was the most predictive parameter. There was no significant influence of intrauterine growth retardation, body mass index and age at the start of treatment, or parental target height. Bone maturation was significantly retarded over CA by a mean value of 1.1 +/- 0.9 yr (P < 0.0001), with a mean bone age/CA ratio of 0.8 +/- 0.2 after a mean treatment duration of 5.1 +/- 1.1 yr. In conclusion, the rapid and almost complete return to normal height obtained in this study supports the need for GH treatment in early diagnosed GH-deficient children. The present dosage may be considered the minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for these children. In addition, it allowed growth at a rate normal for age in patients diagnosed before growth retardation.

Eating and emotional disorders in adolescent obese girls with insulin-dependent diabetes mellitus.

OBJECTIVE: To study eating and emotional disorders in adolescent insulin-dependent diabetic (IDDM) girls. METHODS: 98 adolescent girls, aged 13-19 years, were studied: 15 obese and 37 non-obese IDDM girls, 22 obese non-diabetic and 24 non-obese girls, DSM-III-R eating disorders (anorexia nervosa, bulimia nervosa, eating disorders NOS) and eating habits (snacking, sweet compulsions) were evaluated by a semi-structured diagnostic interview (Kiddie-SADS-E and Eating Habits Interview). Emotional disorders were assessed using self-questionnaires (State-Trait Anxiety Inventory for Children, Beck Depression Inventory, Coopersmith Self-Esteem Inventory). Psychological characteristics were correlated with BMI and, for IDDM girls, with HbA1C. RESULTS: IDDM and non-diabetic obese girls showed high rates of eating disorders NOS (sub-clinical bulimia: 60 and 41%, respectively) and they had more extra-snacks than non-obese girls, suggesting that obesity was the main risk factor for additional eating disorders. However, non-obese IDDM girls had more eating disorders NOS (sub-clinical bulimia: 27%) than did the normal girls (4%). Three IDDM girls had typical bulimia nervosa, while none of the non-diabetic did. The risk of depression was increased by both IDDM and obesity (16 and 18% dysthymia, respectively; 8% in normal girls); both factors cumulated in obese IDDM girls (47% dysthymia). Obesity was linked to marked changes in self-esteem scores and mild effects on anxiety. IDDM had little effect on anxiety and none on self-esteem; it even seemed to preserve the self-esteem of obese girls. Patients with bulimia nervosa had poorer metabolic control than other girls with IDDM. There was no correlation between HbA1C and eating or emotional disorders. CONCLUSIONS: Adolescent IDDM girls are at increased risk of eating and emotional disorders. Obesity appears to be an important factor for psychiatric complications; more obese IDDM girls suffered from eating disorders NOS sub-clinical bulimia), dysthymia, anxiety disorders, depression and low self-esteem (Family Satisfaction SEI sub-score) than did non-obese IDDM girls.

[Treatment with recombinant human growth hormone (rhGH) in children with chronic kidney failure or renal transplantation]. / Traitement par hormone de croissance recombinante humaine (rhGH) des enfants en insuffisance rénale chronique ou transplantés rénaux.

BACKGROUND: Administration of recombinant human growth hormone (rhGH) to children with chronic renal failure (CRF), on conservative treatment or kidney transplanted, may induce acceleration of growth. We report our experience of the first 3 years of treatment in such children. PATIENTS AND METHODS: Eight children with CRF on conservative treatment and six kidney transplanted children were included in a European multicentric trial. All children were given rhGH, 30 Ul/m2 body surface area/week, as daily subcutaneous injections, for 12-36 months. RESULTS: The mean growth velocity in children with CRF increased from 3.8 +/- 0.4 cm/yr before treatment to 9.0 +/- 0.4 (P < 0.001), 6.5 +/- 0.3 (P < 0.002) and 5.4 +/- 0.5 cm/yr, after 12, 24 and 36 months of treatment, respectively. The height gain after 2 years of treatment was 1.2 SD (P < 0.001) with bone age advancement not greater than the increase in chronological age. There was a significant decrease in the inulin clearance after 1 year of treatment. In transplanted children, the mean height gain was less important, increasing from 3.2 +/- 0.4 cm/yr before treatment to 6.2 +/- 0.6 cm/yr after 12 months of treatment (P < 0.001). There was no significant decrease in the mean inulin clearance, but two patients experienced rejection crisis. CONCLUSIONS: A short-term rhGH treatment may improve growth velocity of CRF or transplanted children. The possible role of GH on decrease in glomerular filtration in CRF and on incidence of acute kidney rejection after transplantation remains to be evaluated in a large cohort of patients.

[Laurence-Moon (Bardet-Biedl) syndrome with growth hormone deficiency]. / Syndrome de Laurence-Moon (Bardet-Biedl) avec déficit en hormone de croissance.

BACKGROUND: The features of Laurence-Moon syndrome vary widely from mental retardation, hypogenitalism to retinopathy; the dominant one is progressive neurological involvement, ataxia and spastic paraplegia. Like Bardet-Biedl syndrome, its inheritance is autosomal recessive. This paper describes the endocrine investigation of a new family of Laurence-Moon syndrome subjects. CASE REPORT: The 5 patients (3 girls, 2 boys) in this family of 12 sibs, all suffered from retinopathy, mental retardation and first metacarpal hypoplasia with proximal placement of thumb. All five had had spastic paraplegia since the age of 5-6 years, growth retardation and hypogonadism. Two had had seizures; only one was obese. RESULTS: Four patients (2 girls, 2 boys, aged 19, 15, 18 and 19 years) had low basal plasma FSH and LH levels. They had no FSH-LH response to gonadotropin-releasing hormone; their plasma testosterone and oestradiol concentrations were very low. The growth hormone peak in response to arginine-insulin were low in these 4 patients (1.5 ng/ml; 3.8 ng/ml; 5 ng/ml; 4.8 ng/ml). One boy and one girl were given sex steroids for a few months, with good effect on their sexual characters. Their growth hormone levels remained low (2.9 ng/ml, 6.5 ng/ml). One boy was given FSH and LH analogues with good effects on sexual characters and testicle growth. He was also given growth hormone, and had a growth spurt of 5.5 cm after 9 months treatment. CONCLUSION: The hypogonadism of Laurence-Moon patients seems to be of central origin. It is associated with growth hormone deficiency.

[Eating disorders in an adolescent population with insulin-dependent diabetes]. / Etude des troubles des conduites alimentaires dans une population d'adolescentes souffrant de diabète insulino-dépendant.

The existence of a relationship between Insulin-Dependent Diabetes and eating disorders has recently been observed, but its prevalence and impact on somatic functioning remain poorly understood. These dimensions were evaluated in a population of 52 insulin-dependent diabetic adolescent girls and compared with evaluations of matched subjects from the general population. Results showed that the occurrence of anorexia nervosa is rare, the occurrence of unspecified eating disorders is frequent (35%) and the occurrence of bulimia nervosa is nearly six percent. Poor metabolic control as reflected in blood levels of glycosylated hemoglobin (HBA1C) was found in bulimic subjects and a tendency to be overweight was found in subjects with an unspecified eating disorder. Since such disorders frequently involve dietary restrictions, the role of a restrictive pattern in the occurrence of eating disorders is raised.

[Sugar diabetes after renal transplantation in children]. / Diabète sucré après transplantation rénale chez l'enfant.

Posttransplant diabetes mellitus is ascribed to the use of corticosteroids. Because use of cyclosporine has been associated with increased rates of posttransplant diabetes mellitus, risk factors for this condition have been studied in adults and found to include older age, excessive body weight, and a family history for non-insulin-dependent diabetes mellitus. Only about 1% of children develop diabetes mellitus after transplant surgery. A study of pediatric transplant recipients with diabetes mellitus and of pediatric renal transplant recipients suggested that posttransplant diabetes mellitus may be more common in children with risk factors and may reveal types of diabetes which are infrequent in childhood, e.g., non-insulin-dependent diabetes mellitus which would have gone undiagnosed until adulthood in the absence of corticosteroid therapy. In contrast, corticosteroids apparently had little influence on glucose tolerance in subjects free of risk factors. The effect of corticosteroids seemed to be somewhat less marked than that of renal function impairment.

Effects of nutrient intake on growth, insulin-like growth factors, and their binding proteins in a Laron-type dwarf.

In Laron-type dwarfism, a basal growth rate independent of GH and insulin-like growth factor-I (IGF-I) is maintained. This represents a unique model to further assess the relationship between growth and nutritional status. In a child aged 3 yr, 7 months with severe anorexia, growth was followed in relation to his caloric intake. While receiving 496 Cal/day with 11.6 g/day protein, he grew at a rate of 2 cm/yr (period I). The mean plasma IGF-I level was below 0.07 U/mL, insulin was 3.8 +/- 0.2 microU/mL, and blood glucose was 2.9 +/- 0.3 mM/L. During moderate hyperalimentation with 1280 Cal/day and 38.3 g/day protein (period II) for 7 months, growth rate increased to 9 cm/yr with no significant change in plasma IGF-I and persistence of relative hypoinsulinemia (low response to oral glucose tolerance test). IGF-binding proteins, analyzed by Western ligand blotting, showed that 41.5- and 38.5-kilodalton forms, which were initially low, increased to form a pattern similar to that observed in hypopituitarism. These results suggest that catch-up growth did not require normal circulating GH and/or IGF-I activity. Therefore, nutrition contributes to catch-up growth and achievement of potential statural growth by a distinct cellular effect.

Plasma growth hormone-binding activity is low in uraemic children.

Plasma growth hormone-binding protein (GH-BP) activity was evaluated in two groups of prepubertal children with chronic renal failure (CRF) who had been treated with recombinant human GH (rhGH). Group 1 consisted of eight children (mean chronological age 10.8 years) with advanced renal failure; group 2 consisted of nine children (mean chronological age 6 years) presenting with end-stage renal disease, who were on dialysis. Before treatment the specific binding of (125I)hGH to high-affinity GH-BP was low in the two groups (group 1, 17.3 +/- 1.6% of radioactivity; group 2, 14.2 +/- 1.4%) compared with the mean value obtained in normal prepubertal children (24.8 +/- 1.7%). No significant changes in GH-BP activity were found during the 1st year of GH therapy, although growth velocity and plasma levels of insulin-like growth factor-I increased significantly in both groups. The low GH-binding activity found in children with CRF supports the state of GH resistance. The reason for the absence of a GH-BP response to GH therapy has to be clarified.

Normal growth hormone (GH) response to GH-releasing hormone in children with thalassemia major before puberty: a possible age-related effect.

The plasma GH response to a single iv bolus dose of 2 micrograms/kg BW synthetic GHRH-(1-44)NH2 was evaluated in 13 prepubertal children with thalassemia major (mean age, 7.6 +/- 0.8 yr) with growth retardation and in 15 prepubertal children with nonendocrine short stature. All of the patients showed a significant increase in plasma GH concentration, with a mean peak of 31.4 +/- 4.5 micrograms/L at 15 min (P less than 0.001 vs. basal values; range, 18.4-65 micrograms/L) after GHRH, which was not different from that of the control group of idiopathic short stature children (40.1 +/- 3.4 micrograms/L; range, 21-65.4 micrograms/L). All but 1 of the thalassemic patients had a normal GH response to the arginine-insulin stimulation test. The mean plasma insulin-like growth factor-I level was low (0.12 +/- 0.05 U x 10(3)/L; range, less than 0.02-0.61 U x 10(3)/L). Analysis of these results as well as previously reported data indicating that older thalassemic patients have an impaired GH response indicates that there may be an age-related pituitary and/or hypothalamic dysfunction in thalassemic children. This study also confirms that the insulin-like growth factor-I decrease occurs before any alteration in GH secretion. These changes might play a role in the early growth retardation that occurs in these patients.